TRUTHFUL ORIGINS EVO

"My family tree spreads wide as well. I am a great ape, and you are a great ape, and so are chimpanzees and orangutans and bonobos, all of us distant and distrustful cousins." ~ Katherine Applegate Human Chromosome 2 Fusion: The case of the missing DNA Some History As early as the mid 1800’s when the nuclei of eukaryotes (non-bacteria; we are eukaryotes) were stained, small condensed bodies were noted and called chromosomes, from the Greek meaning “color” and “body”. Because microscopes did not have high enough resolution, some scientists felt humans had 48 chromosomes rather than 46. It wasn’t until 1958 that the true number of human chromosomes was confirmed to be 46. Previously in 1953, many years of controversy regarding the molecule of inheritance was finally agreed upon when Watson and Crick published their famous paper proving that the instructions for inheritance was DNA. Before that many scientists including Linus Pauling thought that the DNA letters of ATCG were too limited to code for the complexity in life and they favored proteins instead as the repository of inheritance. Now we knew DNA in the chromosomes was the molecule of inheritance and humans had 46. Genetic studies of the other great apes in the early 1960s (chimps, bonobos, gorillas, orangutans) showed that they all had 48 chromosomes. Since science knew evolution was true and that we shared common ancestors with the great apes, how then did we end up with 46 chromosomes and evolve from all our common ancestors with 48 chromosomes? Chromosome Basics A chromosome is made up of DNA but also contains different compounds in addition to the DNA. The DNA is combined with proteins called histones that look like small balls in diagrams. DNA normally exists in an unraveled state that appears messy to our eyes. Think of a bowl of cooked spaghetti. When a cell divides and makes new cells the DNA is condensed down into small packets for easier moving. After duplication to make new DNA, the packages - called chromosomes - are lined up at a stage called metaphase and pulled apart with one set going into the new cell and the other set remaining in the parent cell. Note the chromosome below at metaphase and that there is a constriction in the pairs like a belt has been tightened called the centromere that will be discussed shortly. See Figure 1. Figure 1. From nuclear chromosomes to DNA with bases exposed When you look at chromosomes today microscopes and staining techniques have improved to the point where the banding patterns from various dyes result in stunning photos. When we compare human chromosomes to chimp chromosomes for example, the banding is almost identical. To the evolutionary scientist that’s because they share an ancestor. To the anti-evolutionist it’s only due to common design; since humans and chimps are both primates and very similar, a Designer in creating these two separate species would have of course used some of the same DNA. To the anti-evolutionist, humans and chimps never shared a common ancestor. This is based almost entirely on a priori beliefs. If you look at Figure 2 the only way to make all the human (H) and chimp (C) chromosomes match is to take chimp's 12 and 13 and stick them together end on end and now the banding of those two fused chromosomes match human chromosome 2. This is what was announced in 1991, that the fusion point of chimp chromosomes 12 and 13 had been found in human chromosome 2. Figure 2. Fair Use applicable. For education purposes. https://www.kqed.org/quest/586/chromosome-fusion-chance-or-design The Fusion of Our Chromosome 2 This discrepancy in chromosomes between humans and the other great apes theoretically initially presented a problem for evolution since it was settled science that humans evolved from a shared ape ancestor that must have had 48 chromosomes. It was not until 1991 that it officially was solved. A paper from Yale University School of Medicine (yes, evolution is necessary for modern medicine. See Evolutionary Medicine ) showed what happened to the missing chromosome material; it was there all along, or more specifically the DNA. Human evolution from a shared ancestor with the great apes was vindicated by genetics and confirmed the fossil record. To keep the numbering alignment working for the two species, chimp chromosomes 12 and 13 were renamed 2A and 2B in 2004. See Figure 3. Figure 3. JW Schmidt. https://en.wikipedia.org/wiki/Chimpanzee_genome_project#/media/File:Humanchimpchromosomes.png Now it gets interesting and the fusion shows that Evolution is a scientific theory because it can be tested and makes predictions, which means it can be falsified. And as a reminder, the Theory of Evolution has withstood 150 years of testing. Chromosomes have ends on them called telomeres that protect them when copying and moving around. These collections of DNA are called tandem repeats and are the sequence of TTAGGG and then the opposite on the other side of the DNA “ladder” would be CCTAAA . As we age telomeres become smaller and worn down and much research is ongoing into slowing that process down to help us with aging. So, telomeres should not be found in the middle unless the chromosome had become fused in the past. In addition there is a constricted area in the chromosomes best seen in metaphase before the chromosomes are pulled apart. This is where the cell attaches molecular “ropes” to pull them apart into the now two cells. And you can’t have two because that would cause the pulling points to attach at two points instead of one. So besides old telomeres in the middle of a chromosome there should be an old vestigial inactivated centromere that is no longer in use if there was a fusion. If humans evolved from a great ape ancestor shared with chimps that had 48 chromosomes, we should find a fused chromosome with telomeres in about the middle and a second dead vestigial centromere. Furthermore, by looking at chimps 2A and 2B when the ends are put together we can even see where the two centromeres should be. One is active in HC2 now, so we even know where to look to find a second inactive one! See Figure 4 diagram below of what happened and where we can look on HC2 for the evidence. Also look at figure 2 again and see where we can look for the evidence more specifically on HC2. Do you see that the inactivated vestigial centromere should be just below the active one that is presently in HC2? Figure 4. SaudiPseudonym, CC BY-SA 3.0 , via Wikimedia Commons As previously mentioned, in 1991 the area shown to be a fusion site was found to have the sub-teleomere sequences predicted and is located at 2q13 - 2q14.1 (the chromosome is divided into a top “p” and bottom “q” from the centromere). In 1992 the second vestigial centromere was located on HC2 where predicted at 2q21.3 - 2q22.1 . In 2005 the exact fusion point was sequenced. See Figure 5 and find the arrow which points to the exact fusion point. This sends shivers up my spine because we are looking at an event that happened millions of years ago in a single individual of our distant ancestors. And he or she spread that chromosome event through inbreeding first in a small population and then to all modern humans (and also Neanderthals and Denisovans). Figure 5. https://i.imgur.com/CJRRUGo.png From: Chromosome 2 fusion - a response to a question on biology stack exchange To further confirm the findings, in 2006 Stefan Muller tagged HC2 with a dye and then applied the same dye tags to an orangutan. See Figure 6. The HC2 photo is on the right and the orangutan chromosomes are on the left. Note that the tagged DNA is found in two human chromosomes 2 (we get one each from a parent) but 4 in the orangutan because the DNA is not in a fused state (chromosomes 12 and 13 in chimps) essentially proving the fusion observation in humans because there are four places with the same matching HC2 DNA in the orangutan as in the 2 locations in humans, exactly as predicted. Figure 6. Human tagged karyotype on the right, Orangutan on the left. From: Verena Schubel, Stefan Müller, Department Biologie der Ludwig-Maximilians-Universität München., CC BY-SA 2.5 , via Wikimedia Commons Here is the explanation of his experiment: " DNA of the human chromosome 2 was labeled, applied to Orang-Utan (left) and human metaphase chromosomes (right) by fluorescence in situ hybridization and detected in green. While in the human metaphase spread only the two copies of chromosome 2 were detected, in the Orang-Utan metaphase spread the two original chromosome pairs were painted: Human chromosome 2 is the evolutionary derived fusion product from two separate ancestral chromosomes. In non-human primates - like for example in the Orang-Utan (chromosomes on the left side) - as well as in several other mammals, two chromosomes are observed which carry human chromosome 2 orthologous genes and syntenic segments of orthologous DNA sequences. The fusion in human 2q13-14 at approximately 114 Mbp of the human reference sequence ( see Ensembl ) occurred after the split of the human and chimpanzee lineages from that of their last common ancestor.” Here is a short summary of the fusion and how it relates to human evolution. Also discussed is how an individual with this chromosomal number could reproduce and how that 46 number could become fixed in a small population and then spread. Lastly, some of you may be wondering how going from 48 to 46 chromosomes could have happened. The 46 number can actually occur in just two generations with inbreeding. A Punnett square at the end of this article shows how it probably happened. Potential Objections Various people have raised some observations that they perceive as negating the claim that HC2 is a fusion product. All of them have answers, however. HC2 is definitely a product of a fusion of an ancestor to humans, specifically what now resembles chimp's 12 and 13 chromosomes. 1. There is too much degradation in the fused telomeres. This is discussed in an online debate between the Discovery Institute and Carl Zimmer: https://carlzimmer.com/the-mystery-of-the-missing-chromosome-with-a-special-guest-appearance-from-facebook-creationists/ 2. The DDXL112 gene in the fusion area. This and several other objections are addressed in a 28 min video. https://www.youtube.com/watch?v=qVeriF1OL54&t=762s 3. The claim that there are numerous telomere sections throughout chromosomes so a fusion by noting telomeres in the middle of chromosomes is unjustified. Why there are short telomere sections found in chromosomes is explained by Graeme Finlay in his book, "Human Evolution: Genes, Genealogies, and Phylogenies" . This book is actually the finest presentation of DNA evidence for human evolution that I have ever found. Highly recommended. This from his section on " Old scars on DNA ", and how these scars are randomly generated but shared across humans and the other great apes, indicating shared ancestry. "Some 50 short, well-conserved interstitial telomeric repeats, (TTAGGG)n, are present in the human genome. Sequencing studies indicated that they arose as distinct insertion events, probably generated by the action of the enzyme telomerase, which has the function of adding TTAGGG units at the authentic telomeres. These inserts have the characteristics of emergency DNA repair patches that were recruited to hold double stranded breaks together." (p. 146-147). Numerous DNA patches and repairs that are randomly produced and randomly repaired are exactly shared between humans and the other great apes. Some of these patches contain telomeres so the anti-evolutionist objections are disproven. To understand how DNA repair patches point to near proof of human evolution as explained by Finlay, see the short blog on evolution and DNA patches . Instead of being a problem for evolution, interstitial telomeres actually support evolution because they nest in evolutionary phylogenetic trees confirming evolution. As usual, a close examination of anti-evolutionist objections reveals motivated reasoning and lazy "research"; pushing out "possibilities" without testing them and not knowing the literature. 4. Chromosomal fusions and splits occurred in our distant past. As early as the 1980s scientists were able to piece that history together. During meiosis crossing over occurs and also chromosome sections can break out and be inserted in the opposition direction (inversion = Inv). In comparing our chromosomes to other great apes, insertions, deletions and inversions were noted and these events can be seen as part of our genetic history. Roman numerals refer to chromosome numbers. 5. A comment regarding a person making claims that HC2 can't be a fusion. Comments from a geneticist on Reddit and the creationist Tomkins . 6. Actually there was some shuffling of both ends of the chromosomes before the fusion took place. A study published in August of 2022 appears to have narrowed the fusion time between 800,000 and 1 mya before modern humans, Neanderthals and Denisovans split off. In addition, another study showed there probably was a bottleneck in our ancestors about that time and so it would have been easier for the fusion to become fixed in a smaller population. From: Hawks, John. August 31, 2023. When did Human Chromosome 2 Fuse? Full explanation and discussion in: https://johnhawks.net/weblog/when-did-human-chromosome-2-fuse/?fbclid=IwAR0ScYtuG_g7a8ZcGkDWKQOdkrT4enoI4VnWBlPuf7l3SnL2ziSPgFaqEhM Robertsonian fusions, which are a different type involving centromeres near chromosomal ends, are not rare; they occur in 1:1000 people so if you are in a city of 2 million there are about 2,000 people walking around with 45 chromosomes and are perfectly healthy and probably some may be ignorant that their chromosome number is unusual. They have the same basic DNA we have but one less chromosomal luggage piece. After the HC2 fusion event, other mutations occurred to our chromosome 2 including in the fusion site, and duplications of chromosome 9 moved into 2. When compared to the orangutan genome, HC2 carries two inversions. The first shows after a break after orangutans and the second differentiates chimps from gorillas. This all is explained elegantly by evolution but not by common design. There is no reason these inversions happened as they did unless common descent is true; they do not fit into common design as an explanation. See below: What fossil evidence is known that points to the earliest hominid candidate branching from chimps and bonobos 6 - 7 mya? Looking for Mr. Goodlink? - https://pandasthumb.org/archives/2024/07/looking-for-mr-goodlink.html?fbclid=IwZXh0bgNhZW0CMTEAAR1tqB8ZjQYkNc9xiw7Y-JeQu8kHQp-Xv_F4lkb0RGcrO_cTtbgMgHbKVAQ_aem_gSjMcNZ_alEk8DVfk13n3w#more Summary - all the potential objections put forward to discount that our chromosome 2 is a fusion that I know of have been answered. There are no rational reasons why HC2 is not a fusion that I am aware of. Lastly, some of you may be wondering how going from 48 to 46 chromosomes could have happened. It actually can occur in just two generations with inbreeding. A Punnett square at the end of this article shows how it probably happened. Conclusion Why then did I choose shared ERVs and not HC2 fusion as one of my two best examples for evolution? Because I suppose someone could still claim that chimps and the other great apes were created first with 48 chromosomes, and then two chromosomes were fused together when creating humans. That’s possible I guess, but HC2 fusion is still best explained by evolution and not common design. How it was determined shows that evolution is science. With shared ERVs, there is no getting around that these old parasitic viral tags rise to the level of proof of evolution and common ancestry in humans ( see shared ERVs, this site ). Indeed, in my opinion all attempts to date have failed to discount shared ERVs and human evolution. Human chromosome fusions are not rare. For example it's not rare for Robertsonian Translocations to occur where two chromosomes accidentally fuse during meiosis. Often they have the centromeres near the tips (acrocentric chromosomes), so little DNA is damaged. The person is usually phenotypically normal but since they have 45 instead of 46 chromosomes they may not know this until they try and have children. This occurs in 1:1,000 people so in a city of 2 million for example, there are 2,000 people walking around looking normal but with 45 chromosomes instead of 46! There is even a case of three children that are normal physically with 44 chromosomes because two people who had 45 chromosomes from Robertsonian translocations mated. Human Chromosome 2 is a fusion of an ancestor that appears similar to current chimps' chromosomes 12 + 13, now called 2A and 2B (our closest living relative). We did not evolve from modern chimps but we shared a common ancestor about 6- 7 million years ago with them. The fusion happened after we split from our chimp/bonobo ancestor. It is consistent with human evolution and our shared ancestry with our great ape cousins. It represents human evolution and an example of "macroevolution". References There's Proof of Evolution Hiding in Your DNA https://www.youtube.com/watch?v=2GfKZlTRNjA Human Evolution: Genes, Genealogies and Phylogenies. 2013. Finlay, Graeme. 2021 Paperback ed. University Printing House, Cambridge, CB2 8BS, UK. 359pp. Addendum : going from 48 to 46 chromosomes in a pre-human population with just two generations. It would then need to be fixed. Eggs are represented on the vertical axis and sperm on the horizontal axis. Diagram by the author.

Is the Theory of Evolution vital for good medical practice? "Not one example can be put forth of the need for evolution (or belief in its tenets) in order to practice modern medicine." ~ Robert Mitchell, MD. 11/22/2005 "If evolution were thrown out of consideration, it would have no negative impact (in medicine)—it plays no necessary role in either the teaching or practice of medicine." ~ David Menton, PhD. 7/21/2008 "No biological problem is solved until both the proximate and the evolutionary causation has been elucidated. Furthermore, the study of evolutionary causes is as legitimate a part of biology as is the study of the usually physicochemical proximate causes." ~ Ernst Mayer, 1982. Introduction Are those statements by Drs. Mitchell and Menton true? That there are no examples where an evolutionary context adds to understanding of the human body, behavior or disease? Where evolution plays no role in treating patients or developing new treatments? I often hear the religious tell me that evolution has no role in the practice of medicine, and indeed can be harmful. I would like to assert that the answer is yes and no. A medical provider can practice clinical medicine without considering evolution; it just won’t be the best medicine. One can’t really understand the anatomy, physiology and psychology of humans without evolution. And for researchers at medical schools and other research institutions, it’s vital for them to ground their medical work in evolution. For example, a surgeon can be taught to diagnose a gallbladder problem and to remove it laparoscopically. Someone can learn to change a tire on a car without knowing how the car works or even how to drive it. But that person would be unable to diagnose a problem in the auto’s electrical or transmission, let alone work on improved designs for future models. Likewise, surgeons for example don’t necessarily need to know the origins of this organ or why we are built the way we are with all kinds of clues to our evolutionary past (see the section on unintelligent design). In that case ultimate “whys” do not matter much and the providers are acting like highly paid technicians only (not that technicians don’t need to know why something is in their work). But as I will discuss, in basic medical research such as oncology (the study of cancer) and many other areas, evolutionary principles are vital. Mitchell, Menton and other antievolutionists who claim that evolution is not important in modern medicine would do a severe disservice to the medical field by their deleterious approach to health and disease. After all, medicine is an applied discipline that is grounded in biology and biology’s foundation is evolution. American medical providers (and probably those in other countries) are now pressured more and more to use algorithms in medicine - without necessarily knowing why the steps are there. Theoretically this should help medicine to be more standardized by various providers that are trained differently (MD, DO, DNPs, PAs e.g.), reduce unnecessary testing, and reduce missed diagnoses. However, it also potentially disconnects the provider from novel thinking and curiosity. For example, if you had a complicated problem with your car transmission, would you want someone who has actually taken one apart, who knows how they work, what factory it was made in (its origin) and if that year the factory had manufacturing issues? Or would you use a mechanic who just knew it was broken and supposedly had been taught what to do only to fix it? Today that can mean just replacing part after part until it is fixed. Expensive diagnostic tools to read error codes can help narrow the origin of the problem, but auto systems are interconnected so one still needs to understand the basic interplay and integration of the car systems. Knowing ultimate “whys” is a much superior approach. What if a problem arises that does not fit the medical algorithms? I can tell you from experience that the human body has not read the medical books. And that transmission problem? I’m sure that someone who actually knows how that complicated machine works will be much better at diagnosing and fixing it properly. The “why” can be so important. Have a patient with an anemia? What about just giving them iron without knowing what type of anemia it is? If it is an iron deficiency anemia isn’t it mandatory that you find out why -where the red blood cells are being lost or why they not being produced? Anti-evolutionists insist that medical providers don’t need to understand the evolutionary history of life and disease to practice medicine. Some claim that there is not even one example of why knowing evolution is important in medicine. But is that true? Evolutionary Medicine This new field of medicine became established in the 1990s, especially with the publication of the 1996 book by Nesse and Williams, “Why We Get Sick: The New Science of Darwinian Medicine”(1). Nesse, now at the Center for Evolution and Medicine at Arizona State University, notes that Evolutionary Medicine (EM) “… is the field at the intersection of evolution and medicine… Instead of only asking how bodies work and why some people get sick, EM also asks why natural selection has left all of us with traits that make us vulnerable to disease. Why do we have wisdom teeth, narrow coronary arteries, a narrow birth canal, and a food passage that crosses the windpipe? Evolution explains why we have traits that leave us vulnerable to disease, as well as why so many other aspects of the body work so well.”(2). Low notes that EM “… infuses traditional medical thinking, which primarily centers on proximate explanations and reductionist approaches, with evolutionary concepts to offer ultimate explanations for why diseases may occur, thus providing a more complete framework for understanding the origins of disease risk”. (3) As has been noted, “An evolutionary view of medicine can be extremely useful to help patients understand the “whys” of medicine… why are many cancers more common now than they used to be? Why do so many people struggle with obesity? [they’ve inherited survivor genes]. Why does depression exist?”. (4) Centers for Evolutionary Medicine This new field is so promising that multiple departments and centers for EM have been established at medical schools and universities in America and around the world (in the UK for example). UC Berkeley includes a section on evolution and medicine in its Understanding Evolution course. Johns Hopkins University offers a PhD through their Center for Functional Anatomy and Evolution. UCLA has established an Evolutionary Medicine Program and interdisciplinary center that combines faculty from Biology, Medicine, Geography, Psychiatry and Psychology, Anthropology, Veterinarian Medicine, and other allied disciplines (5). As previously noted, a significant research center for EM is located at Arizona State University and its Center for Evolution and Medicine. Several top American medical schools use or have used paleontologists to teach anatomy to their medical students. Why would top medical schools like The University of Chicago’s Pritzker School of Medicine have a fish paleontologist teaching human anatomy to medical students (Neil Shubin, author of “Your Inner Fish”)? Why would the Northeastern Ohio Medical University have probably the most famous cetacean paleontologist alive today teaching human anatomy to medical students (Hans Thewissen)? Because a doctor won’t understand the crazy course of the Recurrent Laryngeal Nerve in the human neck without evolution (see the section on unintelligent design), nor why our ears are attached to our heads with vestigial muscles, why human males develop inguinal hernias (embryologically the testes develop at the level of the heart as they are in adult sharks for example, and in humans they must move all the way down into the scrotal sac at birth, leaving a tract that can later delaminate and open), why our coccyx (tail bone) is derived from smaller fused bones that hark back to when our ancestors had tails, why humans are rarely born with tails that can even be moved, why the plantaris muscle in the human calf is vestigial in humans and even missing in about 10% of the population (it flexes all the digits at once in the monkey - good for swinging in trees), why we form goose bumps to cold and surprise, and other anatomical features that can only rationally be explained by our evolutionary roots. We can’t really understand human behaviors unless Psychology and Psychiatry are ultimately rooted in evolutionary theory. For example, why do people not understand correct odds and continue to invest badly? Where does nationalism and tribalism come from if not from millions of years of selection that kept us alive and those we love safe when we were hunter-gatherers? Why do men and women often approach partnership so differently due to biological factors of investment cost in offspring - which can, like tribalism, be overcome. We don’t need to be slaves to what was successful in our past evolution but may be harmful to us now. Journals have been established for publishing research in EM. These include ISEMPH, the International Society For Evolution, Medicine & Public Health which publishes through Oxford University Press a journal of the same name, and The Evolution & Medicine Review. There is a database of 1600 online teaching resources for EM in EvMedEd. Cancer Perhaps in no other field of medicine has an area of research benefitted more from an evolutionary perspective than oncology. Oncology is the study and treatment of cancer. Cancer is basically cells that are no longer under control by the body. In order to grow, spread (metastasize), and evade the immune system they must acquire a whole host of mutations beneficial to them. As they grow they crowd out normal cells, use up precious energy, and cause destruction. Joshua Swamidass, MS, MD, PhD and on the faculty of the Washington University School of Medicine in St. Louis where he is an Associate Professor of Laboratory and Genomic Medicine, writes about the importance of EM to understanding cancer: “Evolutionary theory “makes sense” of cancer, giving us critical insight into how it works. This has become particularly clear in recent years. Now, we can sequence all the genes in a patient’s cancer, and see how they change over time as cancer evolves. Cancer evolves with the same evolutionary mechanisms that drive the evolution of new species. Like breadcrumbs marking a path through a forest, cancer evolution leaves information in cellular genomes that evolutionary theory can decode. Going the other direction, cancer makes sense of evolution too. Cancer itself is not evolution at the species level. However, it validates the mathematical framework underlying modern evolutionary theory. Cancer cells evolve multiple new functions in an evolutionary process, creating precise genetic signatures of common descent. At both a genetic and functional level, cancer follows patterns explained by evolutionary theory…In cancer… we can directly verify that evolutionary theory correctly reconstructs a cancer’s history, including its ancestry. We see all the same patterns in cancer evolution that we do in the evolution of species: neutral drift, nested clades, novel functions, and positive selection. The same math, software, and theory that is used to study the evolution of species works for cancer too. From a biological point of view, it is now clear that cancer is an evolutionary disease. Cancer biologists use evolutionary theory because it is useful and accurate, not because they are pushing an “evolutionary agenda.” In cancer, cells evolve a set of new functions. These functions are beneficial to the cancer cell, but ultimately lethal to their host. And cancer must do much more than just grow quickly. Nonetheless, in all cases, more than just rapid growth is required for cancer to develop. Several new functions are required. Ultimately, many cancers will acquire more than ten beneficial (to the cancer cell) mutations that enable these new functions. Evolution, it turns out, is a much more useful framework for understanding cancer. From the cell’s point of view, cancer is evolving new functions in the environment of the host’s body. It evolves these functions in an evolutionary process. Cancer exists only because biological systems, including humans, have the intrinsic ability to evolve.” He further writes: “A common misconception about evolution is that it is dominated by natural selection acting on beneficial mutations (this is often what is meant by “Darwinian” mechanism). However, brilliant mathematical work and genetic experiments in the 1960s and 1970s by scientists like Haldane and Kimura demonstrated that evolution, at the genetic level, is usually dominated, instead, by the drift of neutral or near-neutral mutations. So most of the genetic differences between different lineages were either non-functional or not beneficial enough for natural selection…This is one reason biologists say that Darwinian evolution is quantitatively less important than non-Darwinian evolution (e.g. neutral drift, neutral draft, and other mechanisms) in explaining the complexity in genetic differences between species. Cancer evolution independently confirms that neutral theory is correct. We see the same patterns here, but the terminology is different.” “Phylogenetics is foundational to modern evolutionary theory, with deep roots in information theory, population genetics, and neutral theory. It bears repeating, the exact same math, software, and theory that so accurately reconstructs a cancer’s history, is also used to reconstruct the evolutionary history of species…cancer demonstrates that evolutionary theory itself is useful. Going a small step farther, understanding evolution is centrally important in medical research. Fundamentally, cancer is an evolutionary disease. It only arises because life evolves.”(6) [all emphasis mine]. Many other authors agree. “Neoplasms are microcosms of evolution. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. The evolution of neoplastic cells explains both why we get cancer and why it has been so difficult to cure. The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.” (7) “The dynamics of evolution are fully in play within the environment of a tumor, just as they are in forests and meadows, oceans and streams. This is the view of researchers in an emerging cross-disciplinary field that brings the thinking of ecologists and evolutionary biologists to bear on cancer biology.”(8) Aktipis notes in her article “How Evolution Helps Us Understand Cancer and Control it” how cancer cells break down normal cooperation and increase cellular cheating in the body, similar to species that must evolve to move onto other resource areas. She writes, “This ecological and evolutionary perspective highlights new ways of identifying cancerous cells, beyond the typical hallmarks such as excessive replication.”(9). Her book is a wonderful journey through why evolution is so important to modern medicine (24). Somarelli et. al. also note the importance of ecology and evolutionary concepts in understanding cancer: “Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution - and progression - require a deep understanding molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways.” (10). Tollis, Boddy, and Maley in 2017 wrote about how evolution solved Peto's Paradox - why some large long lived animals did not develop cancer, since cancer tends to develop in longer lived organisms as the cells age and total more cell divisions. (11). Hanahan (2022) noted that there are core new functions that cancer cells must acquire to be successful. He goes on to detail some of these changes at the molecular DNA level: "The eight hallmarks currently comprise the acquired capabilities for sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism, and avoiding immune destruction. In the most recent elaboration of this concept, deregulating cellular metabolism and avoiding immune destruction were segregated as “emerging hallmarks,” but now, eleven years later, it is evident that they, much like the original six, can be considered core hallmarks of cancer, and are included as such in the current depiction." https://aacrjournals.org/cancerdiscovery/article/12/1/31/675608/Hallmarks-of-Cancer-New-DimensionsHallmarks-of?fbclid=IwAR3woOcRLSyMeNxCiHEToJJbNukst1osH4wcBf2CjLtpHcKOQJKuJOh3BhM How Cancer Shapes Evolution and How Evolution Shapes Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660034/ DNA Findings Other than oncology perhaps no other area of medicine has benefited from evolutionary principles the past few decades than the study of human genetic diseases and population genetics. Mitochondria - these are small organelles in cells that produce energy for the cell to survive and grow. They are basically only inherited matrimonially (through the mother’s egg). Biologists noted something strange about them early in the study of cytology (cells) compared to the many other cellular organelles. They have their own DNA and it’s in a circular configuration, unlike the chromosomes in the nucleus of the cell, but like bacteria. They have their own ribosomes and tRNAs and these look bacterial. Unlike other cell organelles, they have two membranes, an outer and inner. They reproduce by fission, just like bacteria. They lack the protective mechanisms found in the cell’s nucleus. For these reasons and others it became apparent that mitochondria were bacteria at one time and then were captured in the past. This theory is called the endosymbiotic theory of their origin in our cells and when approaching mitochondria diseases, this evolutionary past is important (15,16). For example, as you might expect they can be affected by antibiotics we give for bacterial infections. Mitochondria are discussed in a separate blog here.Knowing ultimate origins informs the “why" of medical aspects of disease and treatment. Many mitochondrial diseases are genetic due to various mutations (17) and current medical research to cure mitochondrial genetic diseases using CRISPR-Cas9 gene editing techniques look promising (18). This would potentially offer a cure and not just treatment. Knowing the evolutionary bacterial origin of mitochondria is important in treating mitochondrial diseases. Retroviruses - These are viruses that parasitize us differently than other viruses. In the ultimate evil to us, they insert their genetic material into our chromosomes and use the cell’s normal copying systems to instead make more copies of themselves, eventually killing the infected cells and spilling millions more viruses to invade other cells. An example is HIV, the virus that can produce AIDS if untreated. If a retrovirus inserts into a cell destined to become an egg or sperm the insertion will even be passed onto offspring. It can then spread throughout the population to the point it becomes fixed or endogenized. To the surprise of many, it turns out after the human genome was sequenced, 8% of our genome is made up of dead, fossilized retroviruses that we call endogenous retroviruses or ERVs because they no longer can make retroviral offspring. A few years later when the chimp genome was sequenced and compared to our genome, it was observed that 200,000 of these were in the exact same location and many had the exact same mutations. Since retroviruses insert randomly to DNA address (locus) in the chromosomes the only rational conclusion is that these inserted before humans and chimps split from a common ancestry (see the discussion of how this essentially proves human evolution). Common design as an explanation for similarity of DNA across the great apes is thus dead. Besides knowing the origin of ERVs and how it’s only explained rationally by evolution, ERVs are responsible for disease. We already know that some non retroviral genes can cause cancer, such as in breast and cervical cancer. Human ERV (HERV) genetic material has been found in tissue associated with Lou Gehrig’s disease, MS, and schizophrenia (19) and Kurt et. al. note that “The resulting production of envelope (env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches.” (20). Many ERVs are silenced by the host using methylation and other mechanisms as a defense against them. This however, is far from a complete evaluation of ERVs and human co-evolution over millions of years. We have used parts of ERVs to our advantage and co-opted many of them for beneficial uses. For example, one env gene is necessary for producing the placenta and others have been used to help fine tune our immune system in a process called exaptation. It is estimated that 50 - 70% of our genome is derived from viral components and outside elements. Alus - our genome is full of one type of transposable element (TE) called an Alu. They constitute 10% of our genome alone. These are pieces of DNA that can jump in and out of our DNA. We have over a million copies of this TE alone. If we add up all the TE insertions, about 45% of our genome is made up of these elements that jump in and out of our genome, often causing damage. Over a 100 million years ago a gene called 7SL fused to another 7SL at the same time a retroviral infection was occurring. The retrovirus picked up this double 7SL RNA and began to make copies of it and inserting it back into the host DNA. Most of the insertions did not cause problems, but a million insertions did occasionally land into expensive DNA territory. We can identify today damaged gene alleles from Alu and other TE insertions that are responsible for such diseases as hemophilia A & B, familial hypercholesterolemia, severe combined immunodeficiency, porphyria, and Duchenne muscular dystrophy. Many other diseases such as type 2 diabetes, Alzheimer’s disease and cancers of the colon, breast, and lung are victims of genetic susceptibilities due to TE damage. In this case the genes are damaged but not completely destroyed (21). Knowing human evolution is necessary for understanding certain genetic diseases, when and how they entered our germ line and possibly how to correct or control them. Pseudogenes - It has been noted that we have about 20,000 genes that are directly involved in making “us”. These are the genes that produce proteins, commonly enzymes, that control almost everything in our cells. This only represents about 1.5% of all our DNA. Much of the rest is derived from TEs as discussed above and probably mostly “junk” DNA. Indeed, about 98% of our DNA is exactly the same as a chimp’s. But outside that 1.5% are many regulatory and other sequences in our genome that instruct when for example to make products and how long so those elements are probably what really differentiate us from other apes. Scientists have also identified thousands of genes that are damaged and not functional but look like similar normal, active genes. It is thought that there are about 20,000 of these broken, duplicated genes (pseudogenes) but functions have been found for many now that can be partially read so some state the total may be closer to about 12,000. Finlay points out that pseudogenes have always been defined by their original function and if this changed it is still a pseudogene; function does not matter. Christina Sisu notes: “Integrative analyses of cancer data have shown that pseudogenes can be transcribed and even translated, and that pseudogenic DNA, RNA, and proteins can interfere with the activity and function of key protein coding genes, acting as regulators of oncogenes and tumor suppressors. Capitalizing on the available clinical research, we are able to get an insight into the spread and variety of pseudogene biomarker and therapeutic potential. In this chapter, we describe pseudogenes that fulfill their role as diagnostic or prognostic biomarkers, both as unique elements and in collaboration with other genes or pseudogenes. We also report that the majority of prognostic pseudogenes are overexpressed and exert an oncogenic [cancer] role in colorectal, liver, lung, and gastric cancers.” Sen wrote in his paper titled “Relevance of Pseudogenes to Human Genetic Disease”: “Pseudogenes are observed to harbour sequence variations that become degenerative disease-causing mutations when transmitted to their colocalised progenitors through gene conversion event. The issue of pseudogene deregulation in several genetic diseases including cancer is now of the essence in the context of disease progression in humans. Different aspects of the involvement of pseudogenes and their relevance to human genetic disease are recaptured here… Pseudogenes can partially retain or totally resurrect their original functions. Being the paradigm of neutral evolution pseudogenes provide snapshots of the evolutionary history of the human genome. The neutral characteristic of all pseudogenic regions renders them relevant to determine the nature of neutral sequence evolution among different regions in the genome.”(23) Scientists have been using comparative pseudogene analysis for decades to look back at our evolutionary past since we share some of the same pseudogenes (same locations, same mutations) with our ape cousins and thus they confirm our evolutionary history with them. Knowing the ultimate reasons for why we have shared pseudogenes with other apes can explain the origins of some human deficiencies such as our need for vitamin C due to a shared defective gene. We even still make an egg yolk sac and have egg yolk pseudogenes, in the same homologous location as in chickens. And as Sisu writes above, it appears now many of the pseudogenes can have a role in cancer. However, both Moran and Finlay note that pseudogenes can have functions and a proper definition has been confused by more recent researchers. See pseudogenes, this site. Here again a deep dive into where this DNA damage occurred and how will help target therapies. Other examples Obesity - I wrote earlier that many people in developed countries are obese and obesity has been called a pandemic. Many are obese because food is abundant and activity can be diminished. Basically we’ve inherited survivor genes that served our ancestors well thousands of years ago when starvation was always looming but these genes for promoting eating and the efficient extraction of calories are now killing us. Researchers Salazar-Tortosa and Fernandez-Rhodes wrote about this in their 2019 article “Obesity and climate adaptation" where they note using evolutionary perspectives that include genetic changes in metabolic rates, the leptin receptor and brown adipose tissue uncoupling proteins after our ancestors left Africa to increase survivability in colder climates helps us to understand this pandemic via ultimate causes" (12). This will allow medical researchers to attack the problem from its root causes and not just apply drugs or surgery to the issue. Women’s Healthcare - Power, Michael L. et.al. write in their 2020 abstract: “Evolution is a fundamental principle in biology; however, it has been neglected in medical education. We argue that an evolutionary perspective is especially important for women’s health care providers, as selection will act strongly on reproductive parameters, and the biological costs of female reproduction are generally more resource expensive than for men (e.g. due to gestation and lactation) with greater effects on health and wellbeing. An evolutionary perspective is needed to understand antibiotic resistance, disease and health risks associated with mismatches between our evolved adaptations and current conditions, and the importance of breastmilk as a biochemical signal from mothers to their babies. We present data that obstetrician-gynecologists’ views regarding inclusion of evolution within their training is generally positive, but many barriers are perceived. Requiring coursework in evolutionary medicine prior to enrollment in medical school may be a solution.” (13) Sickle Cell Disease and Malaria - 1 million people were dying every year from malaria as of 2010, especially children. Individuals with sickle cell trait, a genetic defect, have red blood cells that are less accommodating to the Plasmodium parasite’s life stage that infects red blood cells. A homozygote normal hemoglobin (HbA/HbA) individual will suffer from malaria more than an heterozygote individual (one HbA and one HbS gene). Those who are homozygous for sickle cell trait having two HbS genes (HbS/HbS) suffer and die more frequently from sickle cell anemia and disease. Thus it is impossible to understand why sickle cell disease persists and is not removed by natural selection without understanding the evolutionary roots of the disease. In this case the carrier state, the heterozygous condition, is being selected for at the expense of the homozygous normal and homozygous sickle cell diseased individuals (14). Ancient DNA As a Tool for Medical Research - "Paleogenomics can help elucidate the genetic basis of modern diseases, including inborn errors of immunity that impair the response to infections, providing a tool for drug development... These discoveries have shed new light on the origins of human populations, their migratory history, and the extent of admixture between humans and ancient, now-extinct hominins, such as Neanderthals, and between modern human populations. However, ancient genomics is also of value for medical research, making it possible to reconstruct the history of human health over time, including past epidemics. This research allows increased understanding of the present-day links between genomic diversity and disease... It is increasingly clear that paleogenomics is a discipline of interest well beyond purely anthropological questions, as it can provide answers to questions of fundamental importance in medical research. It may be time to adopt a slightly rephrased version of Theodosius Dobzhansky’s famous phrase: “Nothing in medicine makes sense except in the light of evolution.” https://www.nature.com/articles/s41591-023-02244-4 Conclusion Anti-evolutionist medical providers have claimed that evolutionary theory has no use in modern medicine. A review of the many Centers for Evolutionary Medicine would indicate otherwise. It is true that one can practice medicine on a more superficial level without considering evolutionary principles if all that is required is a “fix it” mentality. However, in research and often in clinical settings, needing to know ultimate causes is necessary to apply or develop potential effective treatments for various human conditions and this requires an evolutionary context and lens. Ernst Mayer was correct. Numerous examples were discussed revealing the willful ignorance of those physicians who think the best medicine can be practiced without an evolutionary perspective. The study of cancer especially is incredibly illuminated and mirrors evolution, along with the newer genetic medical disciplines as Swamidass especially discusses. Citations 1. Darwin in medical school. 2009. Baker, Mitzi. Stanford Medicine Magazine. Stanford School of Medicine. https://sm.stanford.edu/archive/stanmed/2006summer/evolutionary-medicine.html 2. What is Evolutionary Medicine: Ten Questions Answered. 2016. Randolph Nesse. https://evmed.asu.edu/blog/evolutionary-medicine-top-ten-questions 3. https://www.sciencedirect.com/topics/medicine-and-dentistry/evolutionary-medicine 4. https://askabiologist.asu.edu/evolutionary-medicine-doctors 5. https://www.evmed.ucla.edu/people/ 6. https://peacefulscience.org/articles/cancer-evolution/ 7. https://www.nature.com/articles/nrc2013 8. https://www.sciencedaily.com/releases/2006/11/061117114616.htm 9. https://www.scientificamerican.com/article/how-evolution-helps-us-understand-cancer-and-control-it/ 10. https://academic.oup.com/mbe/article/37/2/320/5603308?login=false 11. https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0401-7 12. https://academic.oup.com/emph/article/2019/1/104/5509505?login=false 13. https://academic.oup.com/emph/article/2020/1/60/5816598?login=false 14. https://www.pnas.org/doi/pdf/10.1073/pnas.0906198106 15. https://www.nature.com/articles/d44151-022-00006-8 16. https://www.labroots.com/trending/microbiology/2279/how-bacteria-became-mitochondria 17. https://www.medicalnewstoday.com/articles/320875#disease 18. https://pubmed.ncbi.nlm.nih.gov/36275864/ 19. https://theconversation.com/humans-are-8-virus-how-the-ancient-viral-dna-in-your-genome-plays-a-role-in-human-disease-and-development-192322 20. https://pubmed.ncbi.nlm.nih.gov/20477095/ 21. Human Errors: A Panorama of Our Glitches, from Pointless Bones to Broken Genes. 2019. Lents, Nathan H. Houghton Mifflin Harcourt. 223pp. 22. https://pubmed.ncbi.nlm.nih.gov/34165724/ 23. https://onlinelibrary.wiley.com/doi/abs/10.1002/9780470015902.a0025002 24. The Cheating Cell: How Evolution Helps Us Understand Cancer and Treat It 2020. Princeton University Press. 256pp. Amazon books Summary: "When we think of the forces driving cancer, we don’t necessarily think of evolution. But evolution and cancer are closely linked because the historical processes that created life also created cancer. The Cheating Cell delves into this extraordinary relationship, and shows that by understanding cancer’s evolutionary origins, researchers can come up with more effective, revolutionary treatments. Athena Aktipis goes back billions of years to explore when unicellular forms became multicellular organisms. Within these bodies of cooperating cells, cheating ones arose, overusing resources and replicating out of control, giving rise to cancer. Aktipis illustrates how evolution has paved the way for cancer’s ubiquity, and why it will exist as long as multicellular life does. Even so, she argues, this doesn’t mean we should give up on treating cancer―in fact, evolutionary approaches offer new and promising options for the disease’s prevention and treatments that aim at long-term management rather than simple eradication. Looking across species―from sponges and cacti to dogs and elephants―we are discovering new mechanisms of tumor suppression and the many ways that multicellular life-forms have evolved to keep cancer under control. By accepting that cancer is a part of our biological past, present, and future―and that we cannot win a war against evolution―treatments can become smarter, more strategic, and more humane. Unifying the latest research from biology, ecology, medicine, and social science, The Cheating Cell challenges us to rethink cancer’s fundamental nature and our relationship to it."

“Expanses of duplicated DNA are situated around our genomes…Genome science has revealed that 5% of our genome is composed of large duplicated segments of DNA or segmented duplications (SDs). Each such duplication that is a common genomic character of our species must have occurred in an ancestor that was common to us all… Any duplicon [a duplicated unit] shared with another species establishes common ancestry” ~ Graeme Finlay Introduction New genes arise naturally. It happens all the time. Where can we find that? In the labs of cell biologists and medical centers with cancer researchers for one thing. Also, other studies have shown that new genes arise with new functions and some de novo. Many of these scientists are Christians and evangelicals; Graeme Finlay, Joshua Swamidass and Francis Collins are examples. It turns out we can prove new genes arise, take on new functions and even develop novel gain of function because cancer tumors begin as a single rogue mutated cell that must evade the immune system and develop novel, new genes in a complex sequential manner in order to survive and grow into tumors of millions of cells. The ability to spread (metastasize) involves many new functions and genes not present in the original normal cell. And this has been demonstrated to happen through random mutations and natural selection, exactly how biologists have demonstrated evolution. See the blog on Evolutionary Medicine, the Cancer section where the Christian and evangelical Swamidass details this. Gene Duplications Biologists have documented for decades that the genomes of animals and plants contain large chunks of duplicated DNA. The human genome contains about 3 billion base pairs and only about 20,000 protein coding genes. That represents only about 1.5% of our genome. Many other genes including regulatory, promoters, inhibitory and enhancer genes are found outside this 1.5%. But the vast majority of that other DNA is derived from viral infections, duplications and jumping genes. They usually represent junk that travels with us. That most of our genome is junk DNA has powerful evidence. See blogs here about pseudogenes as an example of junk DNA that has accumulated in our genome over millions of years often due to duplications and how when shared between species they rise to the level of proof for human evolution. Many have been co-opted for functions and some even have developed new functions, something that most anti-evolutionists claim can’t happen. The Type IA form of Charcot-Marie-Tooth disease is an inherited genetic disease caused by a gene duplication in chromosome 17 resulting in too much production of a protein called PMP22 (1). Ice Fish have a gene that functions as antifreeze that is a duplication of a digestive gene and then evolved a new function. If complexity in organisms were correlated with genome size - which is a prediction of anti-evolutionists since they insist usually that there is no such thing as junk DNA - it is impossible or difficult for them to explain why a species of amoeba has 200x the amount of DNA as humans, or some species of salamanders 100x, or even an onion species with 10x the amount of DNA as humans (Prothero/Shermer debate vs Meyer/Sternberg, 2015). Why would you need that many genes compared to humans to make an onion? This actually has a name as a challenge for anti-evolutionists; The Onion Test (4). Indeed it’s common to find plant species where their chromosomes have undergone complete whole genome wide duplication and not just once. This is called polyploidy in plants and is common. It’s importance is that these duplicated sections are no longer under stabilizing selection pressures since they are just copies. Mutations are often not corrected and the genes are allowed to evolve into new genes or to degrade and become pseudogenes. “The prevalence and recurrence of polyploidization in plant species make it one of the most important evolutionary events in plants, and as a result, polyploidization is an extensively investigated research field. Due to the rapid development of sequencing technologies, there is increased evidence to support that polyploidization plays an important role in the diversification of plant species, evolution of genes, and the domestication of crops…The occurrence of many independent polyploidization events in plants was found to be tightly associated with the timing of extreme climate events or natural disasters on earth, leading to mass extinctions while possibly facilitating increased polyploidization… Moreover, polyploidization was found to significantly impact species diversification, with subsequent effects on crop domestication and the development of traits with agronomic importance”(2). Copy Number Variants Humans contain many genes that have been copied. Genomic analysis has revealed 11,700 locations in our genomes. Any two people differ at about 1,100 of these and nearly 1,000 variable locations involving more than 50,000 bases have been found. Out of 385 olfactory receptor genes, any two humans can vary in the number of copies we have. Same for taste receptor genes and the number of opsin genes (for vision) we have (3). In other words, individuals can vary slightly in how we smell, taste and see because we all vary in the number of receptor genes we have making sensory receptors. A clear example is in the salivary amylase gene, which begins breaking down carbohydrates (starch) in our mouth. Amylase is also produced by our pancreas. I have a confession; while in training on a few occasions I would send a single amylase test for a patient with an inflammation of their parotid gland to see if it could help show an infection vs a blocked salivary duct vs a tumor perhaps not producing a lot of inflammation. I knew that a high level would result in an emergency notice to a sleeping resident on call because the lab would assume it was due to potentially life threatening pancreatitis. This would result in an unhappy resident as they are pulled out of bed only to find it had nothing to do with pancreatitis. There are ways to differentiate the two sources, including combining it with another blood test like a lipase level or even an isoamylase test, but the latter was not available to me and I purposely skipped combining it with a lipase level (another pancreatic enzyme). Anyway, it turns out that our copy number of this gene can matter. People with more copies digest starch better and individuals of European and Japanese descent have higher number of copies of AMY1 genes than those of African descent. Having more AMY1 gene copies lowers insulin levels via accelerated digestion of starches and reduces the chances of developing insulin resistance and diabetes (3). Segmental Duplications (SDs) In the previous section, it was shown that genes are often copied and duplicated. This can be advantageous as new genes and functions can arise through mutation and selection. Scientists studying animals that live long but yet don’t develop cancer often for example have found one reason is because they have more copies of tumor suppressor genes (elephants and the TP53 gene). It turns out that our genome contains also a huge number of copied large chunks of DNA segments containing genes that are shared by all of us, in contrast to various copy number in different human groups and individuals. About 5% of our 3 billion base pairs represent large duplicated DNA segments called segmental duplications (SDs). Recall that 8% of our genome is made up of ERVs that originally were placed randomly millions of years ago by retroviral infections. See ERVs. SDs have been defined as copies of large sections of DNA (> than 1,000 bases) that show a greater than 90% similarity with copies (3). These copies can even be found on different chromosomes or crammed into areas near centromere or telomere repeats. When these large blocks of duplications occur, they can destabilize genomes, cause genetic diseases, can duplicate genes within them and because they are unique and can be found to be shared across species, comparing them can support evolution to the level of proof (3). Finlay notes the following examples: Scientists have found that a large fragment of chromosome 1 (100,000 bases long) has been copied and pasted onto the Y chromosome in humans, chimps and bonobos. It is not present in gorillas, orangutans, gibbons or old world monkeys however. Duplicate segments on human chromosome 17 are 24,000 bases long and flank a 1.5 million base region that contains the PMP22 gene. The duplicated segments cause genetic instability and results in a neurological disease. In part of the CD8B1 gene, the first seven of the nine exons [these are the parts left over that are spliced together after the introns are cut out during transcription processing] has been duplicated as a truncated pseudogene that is present in humans, chimps and gorillas but not orangutans. One end of the duplicated segment has a breakpoint precisely in the same spot in each species having the pseudogene. A segment of DNA 76,000 bases long has been copied from chromosome 9 to chromosome 22, promoting mis-pairing of the chromosomes during cell reproduction and promoting a translocation between the two chromosomes that generates two genes fusing to form a chimeric BCR-ABL fusion gene that is a cause of a type of leukemia (CML). “The paired blocks of DNA are found in the genomes of humans, chimps and gorillas but not of orangutans or monkeys, indicating that the duplication event occurred in an ancestor of the African great apes.” (3) We have a cancer suppressor gene called CHEK2. It is located on chromosome 22 but part of it has been duplicated and inserted into chromosome 16. This event occurred in an ancestor of the great apes because humans, chimps, gorillas and orangutans all have this large duplicated segment. It underwent further duplication; in humans, five of the duplications are interrupted by a particular LINE-1 element, and in two of these cases a corresponding chimp duplicon (SD section) exists (3). These are but a few of thousands of SDs discovered. As Finlay notes, “Duplications of huge tracts of DNA arise as an inevitable outcome of the biochemical nature of DNA and of the enzymatic systems that maintain it. The presence of a particular, randomly arising duplication in multiple cells or in multiple species indicates that those cells or species are monoclonal, descendants of the cell in which the unique structure arose.” The fact that these duplications are unique events and are shared by some of the great apes but not others means we can use them to see if there is a repeatable pattern to their distribution across primate species. "Of all the bases present in SDs in the human genome, approximately 2/3rds are shared with chimps, and were already present in the genome belonging to the ancestors of humans and chimps. Some of these SDs are concentrated near telomeres, and these tend to be younger than SDs found elsewhere. Accordingly, a lower proportion of the telomeric SD’s (50% instead of 66%) is shared by humans and chimps." (3). What all this means If you have hopefully been following along you’ve seen the gene duplications are common. Sometimes they are in large segments of DNA that are copied called SDs (segmental duplications) and these chunks can be in many places in the genomes from next to their original source, to near telomeres and centromeres which involve lots of repeat DNA, to even different chromosomes. "High quality sequence data have allowed the comparison of SDs at single base resolution. The rigorous analysis has confirmed that some SDs are shared by humans and chimps, others by humans, chimps and gorillas and still others by humans, the other great apes and also with old world monkeys such as baboons" (3). If we just simply note which SDs are shared by which groups of primates we can test evolution. Hundreds of SDs have been noted and they generate a primate family tree that is identical to other DNA markers’ trees such as ERVs, DNA repair patches and pseudogenes discussed in the other blogs and sections on this site. If we just compare many SDs and note which are shared between primate groups a family tree based on shared SDs is produced. If evolution was not true a phylogenetic tree could not be produced like this, let alone scores of them using independently derived observations. See Figure 1. Figure 1. Shared Segmental Duplications (SDs) between primate groups. Numerals indicate the numbers of duplication events and when they occurred. See text. From: Finlay, Graeme. 2013. Human Evolution: Genes, Genealogies and Phylogenies. p 204. Figure 4.2. Cambridge University Press. 2021 ed. Social sharing and Fair dealing applied per publisher's web instructions. For example, in Figure 1 above 133 segmental duplications unique to humans have been found. In humans and chimps/bonobos 121 SDs have been found to be shared. Gorillas, chimps and humans have 220 SDs in common. If evolution were not true we could not put together an evolutionary tree from SDs that matched the fossil record, and also the trees produced by shared ERVs, DNA repairs, and pseudogenes. The concept where independent lines of evidence come together and jump towards a firm conclusion is called consilience. We can also approach the same test of evolution with SDs by looking at a single duplication that has kept duplicating, called an expansion. One gene that duplicated more than once can be evaluated in different species. If evolution is true we should find the most recent duplications in species in the newer species and the more recent species should have more copies. And that's exactly what we do find. See Figure 2. Figure 2. Expansion of the SPANX gene family through primate evolution. Gene content is depicted to the right of the phylogenetic tree: X chromosome (thick line), centromere (oval), SPANX genes (open boxes). SPANX-N genes (N), SPANX-N5 (N5), And SPANX-B,C, A1, A2, and D (B, C, A, and D). OWM = Old World Monkeys. See text below. From: Finlay, Graeme. 2013. Human Evolution: Genes, Genealogies and Phylogenies. p 212. Figure 4.6. Cambridge University Press. 2021 ed. Social sharing and Fair dealing applied per publisher's web instructions. The SPANX genes are located on the X chromosome and are largely active in the testes producing a protein in sperm cells. They also can cause premature ovarian failure in women lacking or having damaged genes. This is how Finlay describes the finding of these genes across species. Refer to Figure 2: "In non-primate mammals such as dogs and rodents, a single SPANX-N gene is found located on the long arm of the X chromosome. Primates, in contrast, possess multiple SPANX genes. The gene family has expanded in a stepwise manner through primate history, and the rate has accelerated especially in the great apes. The original SPANX-N gene underwent two duplications in an ancestor of the apes and OWMs (which share three SPANX-N genes), and another duplication in an ancestor of the great apes (which share four SPANX-N genes). Further duplications occurred in the linage giving rise to the African great apes. These species share an additional five genes. These are SPANX-A1, A2, B, and D on the long arm of the X chromosome. Finally, humans have acquired a further gene (SPANX-C) and up to 14 copies of SPANX-B. The flanking and intronic sequences of the SPANX-A to D genes are very similar to each other, indicating that they are located on segmental duplications approximately 20,000 bases long." (3) For those with more knowledge of DNA genomics and perhaps a glutton for evolution DNA punishment, LOL there is a little more regarding the SPANX family of duplicated genes. This is not needed to understand the basic concept of how shared duplications demonstrate evolution to near proof but is featured as an example of how much these scientists know about the genome and the findings that prove human evolution. Reading my blogs on ERVs and DNA repairs would be very helpful if interested. He goes on to note: " The mechanism by which the SPANX-C gene arose has been elucidated. A DNA break occurred in an L1PA7 element [a retrotransposon] that was located some considerable distance upstream of SPANX-B. A segment of DNA (containing SPANX-B) was imported to join the broken ends, and this was selected on the basis of close similarity between the broken L1PA7 element and an L1PA4 element upstream of SPANX-B. The reorganized locus has features of a repair job performed by a non-homologous end-joining (NHEJ). The product contains a chimaeric LINE-1 element, the brand new SPANX-C gene and a chimaeric LTR1B/LIPA7 element." DNA breaks and repairs that are shared between species are powerful evidence of evolution. See my blog on shared DNA repairs here to begin to understand what he is saying and the power of these observations to prove evolution. LINE-1s are a type of jumping gene that randomly inserts into DNA. LTRs are promoters inserted into DNA by retroviruses and are discussed in my ERV section. Conclusion When studying human and the other great ape genomes it was discovered that there are many duplicated genes and many large segments that have been duplicated. We can study the genomes of many species including humans and compare these duplications. When we find the same duplications, defined as greater than 90% of the exact same DNA sequences (ATCG nucleotides) we can be certain that they are indeed the same and represent copies. The only way to have the same duplications at the same chromosomal homologous locations between species is they had to have inherited them from a common ancestor. There is no other rational explanation. Numerous shared duplications can be summed into groups and a phylogenetic tree is produced showing shared common ancestry. The evolutionary phylogenetic trees of segmental duplications match the trees produced by paleontology and the other DNA markers including ERVs, DNA breaks/repairs, pseudogenes, and retroelements. That the same confirming results are produced by independent areas of research means the possibility of evolution being wrong by DNA findings must be essentially zero and represents strong consilience. In addition, some duplicons continued to make copies and within a single family of duplications the number of duplicated copies increases in newer species, as predicted by evolution, and can be nested to form another evolutionary tree from the DNA raw data. As new duplications arise the more recent copies are also found closer to newer species. The comparative segmental DNA duplication findings between primates represents some of the best and most solid evidence we have for human evolution, "macroevolution", and rises to the level of proof in my opinion. References and Citations 1. https://www.genome.gov/genetics-glossary/Duplication 2. https://www.sciencedirect.com/science/article/pii/S2468014119301980 3. Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies, and Phylogenies. Cambridge University Press. 359 pp. Paperback edition. 4. The Onion Test. https://www.genomicron.evolverzone.com/2007/04/onion-test.html

“Natural selection has no analogy with any aspect of human behavior. However, if one wanted to play with a comparison, one would have to say that natural selection does not work as an engineer works. It works like a tinker - a tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him whether it be pieces of string, fragments of wood, or old cardboard; in short it works like a tinkerer who uses everything at his disposal to produce some kind of workable object.” ~ Francois Jacob Part 1 Review and Discussion In the previous part 1 several important points were made about the history of the term junk DNA. Scientists knew especially from the 1960s that there were only about 30,000 genes active in humans. In the last few decades this has been remarkably confirmed with about 20,000 protein producing genes and another 5,000 noncoding genes that produce functional RNA products. Thus, science has pretty much settled on about only 25,000 genes in our genome. This is unlikely to change much or at all in the coming years. To many, this seems difficult to accept that we have the same number of genes as other mammals and yet we appear to be so much more complicated in our brain and social characteristics. There were several reasons why scientists even a half century ago felt that only a small amount of the human genome could be functional. First, the mutation rate of our genome was calculated and confirmed. Based on the number of deleterious mutations that our genome could tolerate, it was predicted that we would only have about 30,000 genes. This was called the argument from genetic or mutation load (1, 4) Secondly, the C-Value Paradox was observed. Some species had very large genomes and others small genomes. Even among closely related species, as with some frogs mentioned in Part 1, there were huge difference in genome sizes. Why would one similar species need a genome so much larger than another? If much of that difference was duplicated and repetitive DNA that built up over millions of years and was mostly nonfunctional, this would be the most parsimonious explanation. The Onion Test by Gregory challenged those who claim that there is little to no junk DNA to explain why an onion needs 5x the amount of DNA compared to a human (2). Third, especially in plants there are many examples of genomes being duplicated, sometimes to 6x the original size. This is called polyploidy and indicates that many species can tolerate this and over millions of years the amount of DNA decreases through mutations - thus the excess DNA was dispensable junk. In modern salmon 96 million years ago a duplication event occurred. (1). Fourth, significant portions of noncoding DNA can be removed from animals without deleterious effects. This indicates it’s most likely junk. If it was mostly or all functional this would not be the result (3). Moran noted that if one totals up all the functional DNA in humans it only adds up to about 8 - 10%. See Table 1 in Part 1 of this blog topic. The other 90% is made up of introns (spliced out during RNA processing), transposons, ERVs and other repetitive DNA. Some even have functions but they are rare. What is defined as functional is any DNA that if deleted reduces fitness. A gene is defined as a DNA sequence that is transcribed to produce a functional product. It’s not the job of the geneticist to prove non function for everything in the genome - 3.2 billion base pairs. One can’t prove a negative. Rather if one is claiming function it is up to that person to show function and not for a scientist to show it does not have function. This is the way evidence works; it’s not up to someone to show unicorns don’t exist, it’s up to unicorn believers to produce the evidence of existence. Those claiming little to no junk DNA need to produce copious evidence of function and not just rare examples. And function means it must have a known product that is functional. Not that it just got transcribed which will be discussed below. ENCODE And then along came ENCODE in September of 2012. The acronym stands for The Encyclopedia of DNA Elements, a consortium of over 400 researchers. There is now an ENCODE 4 in the works. To say that ENCODE made a splash in the news would be a gross understatement. It was all the news in science and the media that year and for years after. ENCODE lists its objectives: “The goal of ENCODE is to build a comprehensive parts list of functional elements in the human genome, including elements that act at the protein and RNA levels, and regulatory elements that control cells and circumstances in which a gene is active.”(5). Importantly, ENCODE defined functional elements as those that produced RNA molecules through transcription, that bind regulatory proteins called transcription factors or that possessed binding sites for methyl groups which can modify the structure of chromosomes (6). Notice that this definition is really a surrogate for function. They did not identify products that were proven to be functional; they primarily assumed that a transcript always indicated a function. There were so many papers that the ENCODE findings were published in a special issue of Nature that year, one of the most prestigious scientific publications in the world (7). Using their definition of function, and relying almost completely on transcription (the DNA was producing RNA products but if they were not immediately destroyed or never produced functioning product was unknown) they found an incredible 80% transcription which they proclaimed meant 80% of the human genome was functional. Anti-evolutionists who were mostly creationists and basically denied any junk DNA were giddy with happiness. Many scientists who could not accept junk DNA or mostly Junk DNA felt vindicated. ENCODE stumbles The definition that ENCODE used for function, transcription = function, soon came under attack by many scientists. It turns out that scientists had previously discovered that about 45% of the human genome was involved in gene activity but also 30% of that were introns that were spliced out and discarded. Only the exons went on to form functional mRNA and other RNAs. Known genes often have large introns and even the ENCODE researchers admitted that only 3 to 8% of the human genome is conserved (1). And genomic conservation between species is one of the best ways to define function because it’s an indication of positive selection in nature; those genes are critical to many species. It turns out that ENCODE was often looking at transcriptions that did not mean anything where their products were quickly destroyed. In other words most of the transcriptions were just genetic noise, spurious transcripts. They were not proven to be functional and have yet to be. “The editors of Nature soon realized they had a serious problem on their hands… Brendon Maher, the feature writer for Nature, took the lead in an article published the very next spring, saying, ‘First up was a scientific critique that the authors had engaged in hyperbole. In the main ENCODE summary paper, published in Nature, the authors had thus far assigned ‘biochemical function for 80% of the genome’. I had long and thorough discussions with Ewan Birney about this figure and what it actually meant, and it was clear that he was conflicted about reporting it in the paper’s abstract.” (1). Maher went on to write that 1% of the genome encodes proteins and 8% of the genome binds transcription factors for a total of 9%. Another 11% he suspected that ENCODE missed due to sampling error giving a real total for function of 20%, the opposite of what ENCODE researchers were claiming (1). This is of course close to the 10% function of our genome that was discussed in Part 1 of this blog. Immediately scientists working in evolutionary biology and genetics wrote papers attacking ENCODE. Eddy (2012), Doolittle (2013), Graur et al. (2013), Hurst (2013), Morange (2013) and Palazzo and Gregory (2014). Moran notes: 1. ENCODE ignored all the earlier scientific evidence and data showing that most DNA is junk. 2. ENCODE ignored all the scientific evidence indicating that much of their “biochemical activity” is spurious and not an indication of biological function. 3. ENCODE and Nature collaborated to deliberately hype their results, thus misrepresenting to the general public the actual conclusions of the experiments. Introns are nearly all junk Evidence that the genome was significantly transcribed was first published in the 1960s. This was called pervasive transcription since most of the genome is transcribed. This was not new to researchers. But researchers also noted that most of the RNA was in the nucleus and very little was mRNA in the cytoplasm. It was later realized that this was explained because it was mostly introns that were being spliced out (1). Introns are mostly junk. “First, intron sequences are not conserved and the lengths of introns are not conserved. Secondly, homologous genes in different species have different numbers of introns, and homologous bacterial genes get along quite nicely without introns. Third, researchers routinely construct intronless versions of eukaryotic genes, and they function normally when reinserted into genomes. Fourth, intron sequences are often littered with transposon and viral sequences that have inserted into the intro and that’s not consistent with the idea of intron sequences being important.”(1) Recall that 30% of the active part of the genome for gene expression (which is 45% of the total genome) are introns in eukaryotic cells. So in terms of function we’re already down to 30% of 45% just with introns alone (13.5% possible function). One of the better reviews of why junk DNA is true and ENCODE wrong was the article by Palazzo and Gregory, “The case for junk DNA” found in PloS Genetics: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351 Functional DNA apologetics The “junk DNA is dead” drumbeat is very much alive. Of course the anti-evolutionist will never give up their belief that there can be no junk DNA because their religious Intelligent Designer would never make a human genome with 80-90% junk, let alone much of it derived from parasitic viral infections (ERVs, LINE-1s, etc.). But it’s also a huge number of secular scientists who can’t or won’t admit that our genome is mostly junk. Below are some of the most common reasons given for expressing hope that a large percentage of the genome will eventually demonstrate actual function as listed by Moran (1). 1. Alternate splicing. It is known that this occurs - that a single gene can produce more than one product mainly but using different combinations of the exons. There are very few proven examples. This won’t save the mostly function assertion. Splice variants are probably due to errors in splicing anyway. 2. DNA-binding proteins. Even if they regulate certain genes, they will always bind random DNA sequences in the nucleus. Models based on “known promoters and termination sites predict that 66 percent of random DNA sequences will be transcribed due to nonspecific binding… In other words, spurious transcription that has nothing to do with biological function will have two characteristics: 1. The transcripts will be rare, and 2. They will be tissue specific. That’s exactly what we see in the transcription data.” 3. Noncoding RNAs and functions. In Part 1 several types of RNA were listed. There are at least 300 rRNA genes and many small RNAs that have functions. But comparatively they have small numbers of genes. snRNAs - 20 different genes, miRNAs perhaps 1000 genes, several thousand piRNAs genes, etc. A type of RNA called lncRNAs have especially attracted “no junk” advocates as they perform many functions. No one knows for sure how many of these genes are present in the human genome. 4. Humans are more complex due to a sophisticated network of regulatory sequences that fine tune gene expression. The ENCODE scientists hope to solve the problem of humans having the same number of genes as other animals despite our complexity because our genes are more highly regulated. However, “most transcription factor binding doesn’t result in measurable changes in gene expression, an idea that’s consistent with nonfunctional binding,… The crucial element that’s missing in most genomic experiments is the negative control… Mike White is a vocal critic of projects that assume function in the absence of a negative control. He actually did an experiment to see whether DNA fragments could promote transcription, and the answer is yes they can… demonstrating that junk DNA can be mistaken for a functional promoter.” 5. Scaffold attachment regions. The idea is that chromatin (makes up chromosomes - DNA and proteins) is organized by DNA that we call junk and is necessary even if it doesn’t code for proteins or RNA. “There’s very little support for the idea that transposon sequences play a direct role in organizing chromatin. Degenerate transposon sequences are much more likely to be exactly as they seem; once-active transposons that have been degraded by mutation.” 6. The extra DNA and passive transcription is a feature of the genome and not an accident. “But this is just a teleological argument and it fails the Onion Test.”. This is probably the conclusion the Christian cancer researcher Finlay reaches in his otherwise excellent book on how DNA proves human evolution (8). 7. Epigenetics. Like the term ‘quantum”, this term is the darling of science the past few decades. Eukaryotes can modify the expression of DNA not by changing the bases or duplication but by silencing some genes by methylation. We know that this can fine tune the DNA from environmental pressures. An example would be starvation and mothers passing along physical influences to their offspring’s DNA. But those are stripped off the DNA and usually don’t persist past a few generations. In addition there’s no obvious mechanism for transferring chromatin markers from somatic cells to the egg cells, especially since those egg cells had already formed before the mother was born (1). Any inheritable epigenetic effects are unlikely to be major effects. 8. Natural selection would remove junk DNA. It’s too energy expensive to maintain it. What is called Neo-Darwinism or the Modern Synthesis has been the major way of looking at evolution. Beneficial alleles would be selected for by natural selection and sweep through a population. This is known as adaptationism. It appears to be wrong at the molecular level or at least over emphasized. What has replaced it or is in the process of that, is neutral theory. “The main tenet of the neutral theory is that the great majority of evolutionary changes at the molecular level are caused not by Darwinian selection but by random fixation of selectively neutral (or very nearly neutral) alleles through random sampling drift…” ~ Motoo Kimora, 1989. This approach is derived from population genetics studies and appears to be correct. People may be surprised that natural selection is thought now not to be the main mechanism for evolution. Species with large populations will have streamlined genomes (bacteria, eg) and species with relatively smaller populations will accumulate junk DNA because it is not harmful enough to be purged by natural selection due to the probability of fixation by random genetic drift becomes significant, and slightly deleterious alleles can be fixed by chance (1). Neutral alleles or near neutral ones in small populations will be invisible to natural selection and junk DNA will accumulate. Since mutations in small populations are mostly neutral and invisible to natural selection, the balance between rates of insertion and deletion determines the size of the genome and the increase in the genome initially is unrelated to the fitness of the individual. This is what population genetics is telling us. Dr. Zach Hancock evaluates junk DNA with expert commentary on an interview with a creationist. The point is that no-junk scientists and anti-evolutionists will often write about all the functions that are being identified for noncoding RNAs (really only about 5,000 genes) but the hopes that all or nearly all of the junk DNA in the genome will be found to be functional, usually by noncoding RNAs, in the future is probably a lost cause. Per the Borg, “resistance is futile” (to deny Junk DNA) and it’s a tragedy that so many good scientists have dug a functional hole they cannot or will not acknowledge is wrong. In part because perhaps of all the grant money involved and subconscious motivated reasoning. Follow the money may be applicable. In March, 2024 Dr. Moran wrote a 9 part blog analysis of a 2024 paper by Niles Walter, PhD Professor of Chemistry at the University of Michigan who supports the view that there is little junk DNA in the human genome. This will help focus the discussion to the various issues that repeatedly arise in the controversy over junk DNA. https://sandwalk.blogspot.com/2024/03/nils-walter-disputes-junk-dna-9.html?fbclid=IwAR1KtPMKrm67N1dCwZdZBD2yTqA3QK8q7otie9Lb2R0t4aMI4D3VgV7CaUE Conclusion Scientists working with DNA and genomes have known that the vast majority of our genome is made up of junk since the 1940s. Introns, transposons mostly from ancient viral infections, ALUs derived from the fusion of two genes plus an ERV insertion, and duplications all have bloated our genome. Attempts like ENCODE to dismiss this have failed if honestly evaluated. The entire ENCODE endeavor for functional claims was a debacle as outlined above. Unfortunately this view appears to still be a minority even in the scientific community. Hopefully Moran’s book will be read widely and discussed and will help to turn the tide to the truth about junk DNA in our genomes. Whether it is 90% as he says or ends up closer to 80-75% remains to be seen but its extremely doubtful it will ever be much less than 75% junk. Creationists and anti-evolutionists will continue to cite ENCODE as evidence for their mostly religious faith commitments and mistaken origin narratives. For the unwary, their claims will probably continue to sound supported and rational when the case is hardly so. Lying by omission is still lying unless they are unaware of why ENCODE should be on their “Don’t Use” list. Transcription involves initiation, elongation and termination. As Moran points out, this entire process is sloppy. Initiation tends to be random; eukaryotes transcribe most of their genomes but as Stuhl writes “little is known about the fidelity… I suggest that ~90% of [RNA] Pol II initiation events in yeast represent transcriptional noise, and that the specificity of initiation is comparable to DNA-binding proteins in other biological process”.(1) Termination also tends to be random. In contrast to bacteria, transcription termination in eukaryotes is a very sloppy business. Because genes are far apart, RNA polymerase [the enzyme that ‘reads’ the DNA to make RNAs] can easily run over the termination site and not stop until it runs into another gene. DNA downstream of a gene is transcribed by accident from time to time which is why much junk RNA transcription comes from regions downstream from active genes (1). Lastly, RNA polymerase sometimes goes in the wrong direction during transcription. “The combination of spurious, accidental low-level transcription at each end of a gene accounts for the observation that a large percentage of junk RNA transcripts occur in the regions around known genes.” (1) The human genome is constantly changing. The average person has about 1000 duplications (see segmental duplications as amazing evidence for human evolution) and 138 unique mutations on average not found in their parents. ALUs are still jumping in our genomes. Evidence shows that ALUs, which make up 11-13% of our genome, are still jumping around - they are polymorphic because everyone has different numbers of them and they have not yet fixed into human genomes. When they land into a gene they often break it and are the cause of some genetic diseases. Transposons by the millions have jumped around in our genomes producing a lot of junk. See Part 1. Introns are cut out and discarded and only the exons go on to produce functional RNAs. The fact that a few introns have functions in no way diminishes the incredible percentage they contribute to junk RNA. Pervasive transcription of most of the genome is part of the genome’s normal activity. According to ENCODE 75% of the genome was being transcribed but 70% of that coverage was from transcripts present at less than one copy per cell. Even ENCODE admitted that this indicated noise and that the transcripts would be less constrained (in effect, junk) (1). Science has known since the 1940s that the human genome and that of other mammals especially have large amounts of junk DNA. And so another topic of misinformation joins the politicization and ideological topics basket we are fighting today. This topic unfortunately has swept up many well meaning scientists to join creationists in spreading the falsehood that junk DNA does not constitute the vast majority of our genome. Citations and References 1. Moran, Laurence A. 2023. What’s In Your Genome?; 90% of your genome is junk. Aevo UTP. University of Toronto Press. 372pp. 2. The Onion Test. April 25, 2007. Genomicron. Exploring genomic diversity and evolution. https://www.genomicron.evolverzone.com/2007/04/onion-test.html 3. https://www.nature.com/articles/news041018-7 4. Surprisingly good article on Junk DNA from Wikipedia https://en.wikipedia.org/wiki/Junk_DNA 5. ENCODE Project Overview. https://www.encodeproject.org/help/project-overview/ 6. https://www.britannica.com/topic/ENCODE 7. Nature: An Integrated encyclopedia of DNA elements in the human genome. https://www.nature.com/articles/nature11247 8. Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. Cambridge University Press. 359 pp. 283 pp. not including References and Index. Paperback edition. 2021 - ISBN 978-1-009-00525-8. Original 2013. 9. Paradigm Shift or Paradigm Shaft? https://sandwalk.blogspot.com/2023/09/john-matticks-new-paradigm-shaft.html 10. Junk DNA, TED talks, and the function of lncRNAs https://sandwalk.blogspot.com/2022/12/junk-dna-ted-talks-and-function-of.html

“Yes, evolution by descent from a common ancestor is clearly true. If there was any lingering doubt about the evidence from the fossil record, the study of DNA provides the strongest possible proof of our relatedness to all other living things” ~ Francis Collins, MD, PhD. 4/6/2007, CNN "The new DNA evidence has a very important role beyond illuminating the process of evolution. It could be decisive in the ongoing struggle over the teaching of evolution in schools and the acceptance of evolution in society at large. It is beyond ironic to ask juries to rely on human genetic variation and DNA evidence in determining the life and liberty of suspects, but to neglect or to undermine the teaching of the basic principles upon which such evidence, and all of biology, is founded." ~ Sean B Carroll, PhD. "The Making Of The Fittest: DNA And The Ultimate Forensic Record of Evolution". Introduction What if I told you that there have been some DNA discoveries that will end any further rational objections to evolution from evolution deniers or doubters? What if this DNA evidence is so sound and robust that it is just what people have wanted who have difficulty accepting evolution? That it involves human evolution and bypasses discussions and moves us to "macroevolution" since it involves humans and the other great apes? What if I told you that when I have presented this to people they have in general failed to understand it because most get lost in the terminology and miss a very simple common theme that underlies all the major categories that address these DNA findings and observations? And that failure may fall to me. Once understood, evolution critics have been unable to discount this evidence supporting evolution. Objections are dismissed when examined closely. Before the DNA findings are introduced by including links below to the blogs, I want to hammer home the central simple concept of all the DNA findings discussed. I will assume that people understand that evolution occurs in populations and not individuals and is change over time (what is evolution?). How this happens is through various mechanisms like natural selection, endosymbiosis, horizontal gene transfer and others and the how is not vital for knowing that evolution did happen due to fantastic DNA findings (see why "what" is first and "how" is often optional). What will be presented is DNA evidence that rises to the level of proof for "macroevolution", which in most cases is a forensic science and of course is accepted in courts of law to be definitive. DNA paternity testing for example. Yes, "proof" technically is reserved for areas of mathematics and philosophy but in science sometimes the evidence is so overwhelming and sound that to deny a conclusion is perverse. Though technically science deals only in provisional conclusions, some scientific theories like Gravity and Evolution are so well supported and tested with predictions that they can be revised but will never be overturned. Origins: common design vs. common ancestry You are a detective at a crime scene involving a shooting and there is a bullet recovered. If you want to connect it to another crime involving a shooting and think it's from someone using the same rifle you can compare the bullets side by side from different crime scenes. A rifle will scratch them exiting the rifle and if the scratches match you KNOW the origin is the same rifle. Forensic ballistics science tried and true. This one rifle thus must be a common source for the bullets found at different sites. Intel purposely puts error code in its chips (personal communication, B.D). If someone steals its design and claims it's just due to similar design restraints and functions they will loose in court to Intel because no one would find and use the same random errors. The competitor chip maker must have copied Intel's. They have a common origin - at Intel. Textbook publishers purposely put errors in for the same reason Intel purposely puts error code in its chips. And in the case of textbooks there is case law that plagiarism took place and the competitor was found guilty. The identical wording in the two textbooks were not developed independently due to similar research and writing but rather due to plagiarism. If independent origins were true they would not contain the same errors. They both share the same origin because they both have the same errors. The copy is not original. How good is DNA evidence? Fantastically good! Paternity testing is nearly 100% accurate. It basically settles cases. We did not need to observe the conception. What about forensics? Same here also. DNA evidence is so important in the courts that they rely on it extensively if available. Even if a crime was not witnessed or recorded, if in context a person's DNA places them at the scene and they claim that they never met the person and was never there, they are usually in deep trouble in the investigation. DNA testing can tell us the genealogy of Egyptian mummies (were you there? - didn't need to be), the identity of crime victims, and of course DNA testing was definitive in solving the Russian Romanov Czar family death controversy. Many crime victims have been found guilty involving erroneous eyewitness testimony and are now having their sentences reversed based on DNA evidence. Chapters of the Innocence Project are widespread in the USA working to get innocent people out of prison. It is disingenuous for evolution deniers to accept the DNA methods and evidence important for solving crimes and for accurate truth searching while rejecting the same source of evidence for species origins just because it disproves and exposes their presuppositions. The Concept When the genomes of different species have been sequenced we can compare the letters that make up the DNA - the ATCG sequences - often billions of letters long. It turns out that most genomes are very active and have been changed often in the past. They end up having parts duplicated, some sections deleted, and some sections spliced out and then inverted when put back in. Breaks are frequent and quickly repaired. Viral parasitic infections in our ancestors repeatedly have inserted their viral DNA into ours (how often are you ill with "viruses" per year, although most of those don't insert into your DNA?). Some genes get mutated and no longer work and are called pseudogenes. These changes are by far random. If we find the same random marks or changes to DNA that are SHARED between species we know that these random changes MUST have occurred before the species split. The odds of having the same random changes occur at thousands of the same homologous locations between species with the same DNA fingerprint base changes independently is mathematically impossible. There is no other rational explanation. Just like the same marks on two bullets means they came from the same rifle and must point to a common origin (rifle), the shared DNA changes must prove a common origin (ancestor) for our analysis. That's the basic observation and conclusion that must be reached. Notice this line of evidence is independent of how similar the bases are, how much DNA the species have in common, how complicated DNA is, where the DNA originally came from, or how the first cell evolved, etc. The DNA from two species or more are just compared for shared random DNA changes. These changes are not original to the DNA. We know this especially because this is how cancer develops starting with one random mutation (two people with the same leukemia type for example have different random mutations) after another producing a nested Russian doll type pattern we can follow backwards to tell accurately the history of the cancer. Two Christians cancer researchers are strong supporters of common ancestry because of their cancer work (Finlay and Swamidass; and of course Collins although his research was not directly in cancer). Structure of the DNA blog entries 1. Discussion and unpacking of the issue 2. A few examples of the hundreds possible 3. Most often how these shared changes nest in evolutionary phylogenetic trees adding another level of proof of common ancestry and evolution 4. Most blogs also have a section on common evolution objections and why they fail and can be dismissed. This often makes the blog longer than it may need be if someone is just interested in how the DNA findings rise to the level of proof of macroevolution. But many reading this will be interested in finding answers to family or friends who are challenging evolution. I really have nearly all objections discussed and dismissed. Really! The advantage of reviewing objections and why they fail is because this will often produce a great window into how purposeful omissions and motivated reasoning reveals their presuppositional beliefs. Scientists in the hundreds of thousands in multiple independent scientific and medical fields accept and work successfully with evolution daily. 5. Multiple links or other embedded teaching items are important to understand the concepts and are included to help with the concepts and details. I have tried to keep them to a minimum. Links can also point the reader to original sources to fact check the blog. And of course those arguing against the DNA discoveries for evolution may wish to spend extra time on the information I provide. We are in another Galileo Moment for anti-evolutionists when it comes to these amazing DNA discoveries supporting evolution. The blogs are best viewed on a computer and not on a cell phone. Here they are; the major DNA findings that rise to proof of evolution The easiest one to read is probably #1 DNA repairs. The most in depth because of the need to address many objections by evolution deniers is #4, ERVs. The blogs will also discuss how we know what we assert for evolution evidence is true. 1. Shared DNA breaks and repairs. DNA breaks frequently in random locations. The repair system grabs whatever DNA is nearby to patch them. This results in random breaks and unique patches/repairs producing a type of one-of-a-kind DNA "scar" by location and uniqueness. If you find hundreds of these exact same numerous scars between two species it must be common ancestry. In addition, comparing the "scar repairs" across many species that are closely related allows us to use DNA to confirm what the paleontologists have asserted. These patterns produce evolutionary trees adding yet another level of proof of evolution. Only a few of hundreds of examples detailed in Finlay's book are presented. 2. Shared segmental duplications. Whole chunks of chromosomes/DNA are often duplicated. This happens in plants where they have even duplicated their entire genomes. If we find these same random duplications of the DNA in the same homologous locations between two or more species we know it had to have happened before the species split. In addition, comparing these same shared duplicated DNA segments and genes across many species that are closely related allows us to use DNA to confirm and test what paleontologists have asserted. These patterns produce evolutionary trees adding yet another level of proof of evolution. 3. Pseudogenes and shared pseudogenes. Our genome contains thousands of disabled genes, knocked out by mutations. They are molecular fossils. When we find thousands of disabled genes that are shared between species and often have the identical mutations it is only rationally explained by the gene being mutated before the species split. In addition, comparing these same shared dead genes across many species often with the same disabling mutations that are closely related allow us to use DNA to confirm what paleontologists have asserted. These patterns produce evolutionary trees adding yet another level of proof of evolution. 4. Shared ERVs between species. This is probably the most in-depth discussion, primarily because so much has been written by evolution deniers to try and dismiss it. Therefore there is more discussion supplied to show why these objections are negated. Basically, there is a group of viruses that insert their DNA into host DNA and use the host machinery to make new parasitic viruses. The most recognizable example is HIV, the cause of AIDS if not treated. We know this retrovirus well and all retroviruses have the same gene types, life cycle, and footprint. They insert randomly to locus. After a retrovirus collects mutations it becomes unable to reproduce and is called an endogenous retrovirus (ERV) because it's inert and fixed in the host population. Most of the ERVs are so degraded only a part is left, called an LTR. These LTRs are still functional however and the host uses them to promote replication of it's own DNA products. Sort of like using old wood from a barn to decorate in a new home. We find many ERVs in the same locations between closely related species and many even have the same mutations that disabled them. Between chimps and humans alone there are 200,000 shared ERVs. They originally came from parasitic retroviruses; we know this for many reasons discussed in the blog. The only rational explanation since they insert randomly and are found in the same locations between species is they had to have inserted before the species split and thus shared a common ancestor between the species. In addition, comparing these same shared ERVs across many species at the same locations that are related allows us to use DNA to confirm what the paleontologists have asserted through fossil evidence. These patterns produce evolutionary trees adding yet another level of proof of evolution. 5. Shared transposable elements between species. Our genome and those of many other species contain thousands of genes that are mobile. These are called transposons or jumping genes. One type, the retrotransposon Alu element is only found in primates. TEs have jumped around genomes for millions of years and insert randomly into genomes. Thus, we can compare genomes from different species and if we find hundreds of the same TEs that match not only in location but also in length and mutations we can be certain that they must have inserted into a common ancestor before the species split. There is no other rational conclusion. In addition, like other DNA findings that rise to the level of evolutionary proof, these also can be nested into phylogenetic evolutionary trees confirming common ancestry, often going into the deep past. Other DNA findings for evolution These are not as strong evolution evidence because they technically can still be accommodated by anti-evolutionists, although they are better explained by evolution. 1. Human Chromosome 2 Fusion. Humans have 46 chromosomes (DNA condensed into small packets like luggage so they can be moved around easily when the cell divides). The other great apes have 48. Since we evolved from shared ancestors with them where did the "extra" DNA go? It wasn't lost, it just got repackaged. Turns out we shared an ancestor with chimps about 6 - 7 million years ago and after breaking off from them what were ancestral chromosomes 12 and 13 got stuck end to end to form our longer #2 chromosome. This is called a Robertsonian Translocation and is not uncommon. Even now 1:1,000 people have 45 instead of 46 chromosomes because of fusions of other chromosomes. All the DNA is there; the only problem is when they want to have children. The 45 and 46 chromosomes can't line up properly. We have fantastic evidence that this fusion happened and it's not the first time in our history that there were chromosomal fissions and fusions. One could still argue that a Great Designer after making chimps, gorillas and orangutans created humans that way for some reason. Possible, but that does not fit well with all the other DNA findings. It's definitely a fusion. 2. Junk DNA. This is controversial even with evolutionary biologists and molecular biochemists. Although a minority position currently, the evidence that most of our genome is junk DNA is so strong that it can't be ignored. To many scientists and especially creationists there is predicted to be little or no junk DNA. But we find 50% - 90% is junk, consistent with millions of years of evolution involving mutations that knock out genes, parasitic viral infections and DNA that jumps around and makes copies of itself (ALUs for example). Also important will be to address and understand why an influential study called ENCODE has conclusions that are wrong or misleading. Conclusion This blog introduces the reader to the major categories of comparative DNA findings between closely related species showing shared changes that rises to the level of proof of evolution, "macroevolution." Several examples are discussed as analogies for how common origins can be determined and common design ruled out. This is how the DNA findings can be viewed also. They are shared random changes to the DNA of species, and different types are discussed including shared ERVs, pseudogenes, segmental duplications, and DNA emergency repairs with unique patches. In all cases the DNA marks are random. Since we find thousands shared DNA marks between certain species the only rational explanation is that these random shared changes must have occurred in a common ancestor before the species split. Equally important, the various shared DNA changes can be nested in hundreds of evolutionary phylogenetic trees confirming paleontology. If evolution were not true, this could not be constructed. In addition to discussing the major categories of DNA evidence for evolution, much discussion in most of the blogs involves addressing potential objections and why they are disproven. This also can be very revealing to establish motivated reasoning and omission of important facts possibly by intent that would falsify the objections.

"Supposedly, summer vacation happens because that's when the kids are home from school, although having the kids home from school is no vacation. And supposedly the kids are home from school because of some vestigial throwback to our agricultural past" ~ P.J. O'Rourke Introduction That the term vestigial has been and is currently being misused is supremely unfortunate. The definition of “ without function” is only half correct. The correct definition is without function, diminished function, or the loss of the original function.  Compounding this many scientists are also unaware of the exact definition.  As will be demonstrated, this has been the correct concept for many decades and applies at the anatomical and genetic levels. It is especially unfortunate that even biology textbooks have not used a proper definition. This issue is similar to the misuse and confusion over the terms atheism and theory in many cultures.  Dictionaries are often of no help in clarifying because their primary function is usage and not delineating best or correct utilization. “The writer of a dictionary is a historian, not a lawgiver. . . To regard the dictionary as an 'authority,' therefore, is to credit the dictionary writer with gifts of prophecy which neither he nor anyone else possesses.” https://www.thoughtco.com/what-is-a-dictionary-1690450 First, if one looks at better definitions of the term we can see that without function or without the original function not only is the more accurate definition but it goes back at least to the 1960’s. This is not a dodge by evolutionary biologists, who have always looked at the concept of vestigial this way. For example: 1. Vestigial structures are those that appear in a rudimentary form in some organisms but in a fully developed, functional form in other, closely related animals; or they are poorly developed structures thought to have been fully functional in ancestors of the modern form (pg. 777) ~ Biology by Leland Johnson 1983 2. [Vestigial] - refers to an organ or part which is greatly reduced from the original ancestral form and is no longer functional or is of reduced or altered function. ~ www.biologyonline.com 3. Vestigial - a degenerate or imperfectly developed organ or structure that has little or no utility, but in an earlier stage of the individual or in preceding evolutionary forms of the organism performed a useful function ~ www.dictionary.com 4. Vestigial - (of certain organs or parts of organs) having attained a simple structure and reduced size and function during the evolution of the species: the vestigial pelvic girdle of a snake ~ Collins English Dictionary, 2014. 5. Vestige - a small, imperfectly developed, or degenerate structure which represents an organ or structure which was fully developed and functional in an ancestor or in an earlier state of development. ~ Dictionary of Biology, Edwin Steen. 1971 Secondly, it clarifies much regarding evolution and what we see in nature. A few examples will be discussed that show the loss of original function applies to many of the structures and facts we observe in nature. 1. The pelvis of modern cetaceans (whales and dolphins) are vestigial. We know this because the entire fossil record shows it changing from associated with a small 4 legged terrestrial animal to the vestigial bone today. Anatomists can identify within the modern whale vestigial pelvis what represents the ischium, ilium, and other pelvic structures. All the atrophied muscles and other structures are still attached in modern cetaceans but at least in males in terms of copulation the vestigial pelvis still has some functions. But they sure can’t walk with them.The current tiny vestigial pelvis sits outside the vertebra and is not attached to any bones. See Figure 1. Figure 1a: Modern whale tiny vestigial pelvises showing anatomical structures that were previously only useful for walking. Several have vestigal femurs and all are not attached to the spinal cord. For educational purposes only. Fair use attribution From: www.http://um.uib.no/fagsider/osteologi/hvaler/b_bekken.htm Figure 1b shows the evolutionary shrunken hind limbs of the fossil Basilosaurid that lived 37 - 40 million years ago (left) compared to a modern Right Whale's vestigial hind limbs (right). Figure 1b. Left = Basilosaurid fossil whale species showing actual size of vestigial pelvis. NOTE ARROW. Magnified view shows bones used for walking. Right = photograph of actual living Right whale vestigial leg bones. From: https://faculty.msj.edu.kritskg/evolab/Site/Vestigial_structures.html Fair use, for educational use only. B. The appendix has been shown to have functions in terms of repopulating the intestinal flora after severe diarrhea and it also contains lymphatic tissue. But the shape and location of the structure indicates it probably served other primary purposes in the past. It is officially called the “vermiform appendix” because in some people it’s very long like a worm and can loop back towards the liver behind the cecum. Not an efficient design for repopulating the gut after a wash out of severe diarrhea. Having a function today does not invalidate it being vestigial. See Figure 2. Figure 2. Diagram of human vermiform appendix. From: Henry Vandyke Carter, Public domain, via Wikimedia Commons C. Pseudogenes are genes we share with other species that have been disabled and knocked out by various mutations. By noting which pseudogenes are shared between species and which are not we can even construct evolutionary phylogenetic trees that rise to the level of proof of macroevolution (see pseudogenes, this site). We have about 20,000 pseudogenes and some have functions. Some are only partially transcribed whereas others have even taken on new functions. They still are vestigial even if they are partially transcribed or have acquired new functions because they have lost their original functions. Finlay notes, Pseudogenes may develop new functions “...but they are defined by their loss of the original parent gene function and not whether they have functions or not currently" ... and "The progressive changes in base sequence provide the history of a pseudogene, and this history defines evolutionary relationships of those species that share the pseudogene. Current functionality is irrelevant to the value of pseudogenes as evolutionary markers." (1)  A few pseudogenes have been noted to exhibit gain of function as noncoding RNAs. (2) Moran notes: “The idea that most duplicated genes will become pseudogenes is consistent with a ton of data and fits well with our understanding of mutation rates and genome evolution. This is an important point. We don't arbitrarily assign the word "pseudogene" to any old DNA sequence. The designation is based on the fact that the duplicated region is no longer transcribed, or it is no longer correctly spliced, or that it carries mutations rendering the product nonfunctional... There are some examples of DNA sequences that appear to be pseudogenes but they also have functional regions. The best examples are duplicates that contain small RNA genes within their introns or genes that contain other functional regions like SARs and origins of replication. In those cases, the inactivated gene is still a pseudogene but the other functional regions are best characterized as something else. There are also quite a few examples of pseudogenes that have secondarily acquired a distinct new function such as producing a small RNA that might have a regulatory function. The review by Cheetham et al. contains several examples of such pseudogenes. They are still pseudogenes but the region may now specify a new lncRNA gene or some other gene such as an siRNA gene.” (3) If so disabled that they have lost all functions they are basically molecular fossils. If they are shared with the same random knock-out mutations between species we are justified in claiming common ancestry as the only rational explanation. For examples and discussion see pseudogenes this site. D. The coccyx is vestigial. It obviously looks like a shrunken tail because it has 5 small bones. It still supports some attachments but it’s small enough that if a Designer didn’t want to make it look like a shrunken tail from our past ape descendants why not just use one or at the most two bones? Since it still has muscles and other tissues attached it still plays a small role in human anatomy, but not it's original function. Figure 3. Diagram of the human coccyx showing how this small bone is really a shrunken remnant of a tail. Functionality is not critical to the vestigial designation. The bone is small enough that one or two bones could easily suffice to be functional instead of having the appearance of 5 fusions. E. Yolk sac . As an embryo we make an empty yolk sac that is vestigial. It still has important functions today such as providing lymphatic and blood cell precursors for the developing embryo but no yolk is produced. Yet it is indeed called a yolk sac because that's what it resembles in other animals that lay eggs. More conclusively, scientists have found 3 human yolk pseudogenes that match the same genes and locations in chickens. We do indeed hark back in deep evolutionary time to a point where our ancestors laid eggs and we have the structure and genes to demonstrate it. Our temporary yolk sac no longer has the function it had in the past and is vestigial. See Figure 4. Figure 4. Human yolk sac which begins development in the embryonic stage and then disappears about the 3rd month. It has important functions but has lost its original evolutionary function. For attribution and additional information, see Why Not Intelligent Design?. Figure 5. Diagram showing three human egg yolk pseudogenes (VIT 1, 2, 3) found also in homologous locations in chickens. Conclusive evidence that the human yolk sac is vestigial, having lost it's original function. For attribution and additional information, see Why Not Intelligent Design?. Third, sometimes a modern species will form an atavistic structure. The DNA is still present to form most of an ancient structure and becomes accidentally turned on. This exposes the ancient connection to it’s past ancestors. These are technically not a vestigial structure because they are uncommon or rare; obviously every individual of the species does not have them, unlike vestigial structures. Notice the decapitated snake in Figure 5. It accidentally grew a leg. It was beaten to death by a homeowner in China, who thought it was trying to crawl up a wall. Notice the leg grew at about the anatomical location we would expect. It did not grow a feather and it did not grow elsewhere like a HOX gene mistake. It grew where an evolutionary ancestor would have had a leg. Figure 5. Atavistic snake leg. From: http://pleiotropy.fieldofscience.com Also: Evolutionary throwback. Snake with foot. Gizmodo.com. 2009, Sept. 15 About 1:5,000 sperm whales grow hind limbs. The DNA instructions for doing that are still present but damaged and normally not expressed. At least six cases are known of whales being caught with hind legs growing. A dolphin was caught in 2006 off the coast of Japan with hind flippers. See Figure 6. Figure 6. Left - a dissected sperm whale atavistic hind limb exposing a femur, tibia and metatarsal caught in 1919 off the coast of British Columbia. Right - a photo of hind flippers growing from a dolphin caught near Japan in 2006. For more discussion of cetacean leg atavisms and attribution see Overwhelming Evidence for Whale Evolution, this site Part 1 Conclusion The proper definition of vestigial is loss of function, diminished function or loss of original function. Repeatedly anti-evolutionists will claim "checkmate" when a function is found for a structure or gene. The finding of a function does not discount that a form can be vestigial. That this complete definition for vestigial is nothing new was demonstrated. It is unfortunate that even within the sciences researchers and teachers may be communicating a wrong concept of vestigial. The actual definition as defined here of vestigial applies not only to structures but also down to the molecular and genetic level and has resulted in unnecessary controversy more recently over pseudogenes in the field of genetics, where some claim there is no junk DNA and few or no pseudogenes (see Junk DNA, this site for example). Vestigial structures, which are present in each individual in a population, were contrasted with atavisms which are rare occurrence of structures that hark back to appropriate evolutionary ancestry. Whales can grow hind limbs but never feathers. Boas and pythons have a vestigial pelvis with rudimentary femurs that are used in courtship which in no way negates them as being vestigial since the original function of the structures was for walking. Citations 1. Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. Cambridge University Press. 283 pp. not including References and Index. Paperback edition 2021 - ISBN 978-1-009-00525-8. Hardback edition 2013. 2. https://onlinelibrary.wiley.com/doi/abs/10.1002/9780470015902.a0020836.pub2 3. https://sandwalk.blogspot.com/2020/01/are-pseudogenes-really-pseudogenes.html#more

“It is generally stated that half of our genome is derived from ERVs and TEs. The application of more-sophisticated software allows the identification of more degenerated (fragmented) TEs has raised this estimate to two-thirds of our genome. TEs have expanded, modified, and elaborated our ancestors’ genomes at least as far back as genetic analysis can detect.” ~ Graeme Finlay, Human Evolution: Genes, Genealogies, and Phylogenies. 2013. Introduction The year 1953 was an incredible year for biology. A paper by Watson and Crick was published that finally ended the search for the source of heredity and cell functioning for all living things. Proteins, the early candidate, had been toppled by DNA. No one could imagine initially that a molecule with only four nucleotide bases - A,T,C,G - could be the holder of the instructions for life. Shown without her knowledge, Rosalind Franklin’s photograph of DNA helped Francis and Crick put one of the final pieces of the puzzle in place. Watson, Crick and Wilkins later received the Nobel Prize in Physiology or Medicine in 1962 for the discovery that DNA encoded the genetic information for life. DNA was thought by many to be like a blueprint, locked away safely in the nucleus. Messenger RNA (mRNA) would make a copy of one side of the unzipped double helix master code and then the mRNA would travel outside of the nucleus to the ribosome factories to help assemble proteins. Perhaps you also have thought of DNA as a master blueprint. Decades later as scientists studied DNA more closely one of those scientists, Barbara McClintock, shocked the world when she demonstrated that large amounts of DNA jumped around randomly copying and pasting back into the DNA, often causing disabled genes. Genomes were not this rigid instruction blueprint as imagined. Indeed, the corn she was studying was made up a whopping 90% of these mobile DNA segments. Humans were found to have nearly 50% of our 3 billion DNA nucleotides made up these mobile elements alone, called transposable elements or TEs. (1) Transposable Elements (TEs) There are over 1,000 different types of TEs, or jumping genes, and about 50% of our genome is made of them but there are only two basic categories of TEs. DNA transposons and ones that use RNA as an intermediate, and are called retrotransposons. No, the retro does not refer to 1960’s bright plastic furniture or 1970’s colors of gold and green. This latter variety must convert their RNA to DNA so it can be randomly spliced into the DNA genome rather than the normal route of DNA to RNA to proteins. The DNA transposons only represent about 2% of our genome and won’t be discussed since they are not necessary to establish evolution (2). The more common retrotransposon TEs are represented by several types important to our discussion. One type makes up 8% of our genome and includes the endogenous retroviruses (ERVs) that were discussed in a section on this site. They are fantastic evidence for evolution and common ancestry by themselves. ERVs have 3 major viral genes (gag, pol, env) for producing their nasty retroviral cellular parasites; an example is the retrovirus HIV that can produce AIDS. Some have lost the env gene and are called LTR-retrotransposons. As was discussed in the section on ERVs, ERVs are fossilized by mutations and the retroviruses are no longer able to produce infectious particles. Most are so degraded only their LTRs are left behind. But initially they were inserted randomly by retroviruses, and if we find thousands of the same ERVs in the same locations between species the only rational conclusion is shared ancestry - evolution. They must have inserted before the species split. The LTRs are made by the viruses before insertion since they will need promoters to get transcription started to make new viral progeny during an infection. Most retrotransposon varieties however do not have an LTR attached and are non-LTR retroelements. Two are especially important for our purposes here. LINEs are long elements of about 6,000 base pairs and SINEs are short and only about 300 bases long. The most common SINE are called Alu elements, named after the bacteria Arthrobacter luteus where their enzyme product was studied. LINE-1 elements alone make up a staggering 17% of the human genome (626,000) and Alus another 11% (1.1 million). There are also L-1 and L-2 retroposons in our genome for another 340,000 (2). Thus LINE-1s, Alus, and LTR retrotransposons alone make up 36% of the human genome! Considering humans have only 25,000 genes and 20,000 protein coding genes make up only 1.5% of our genome, the 50% of our genome that are retrotransposons is amazing. Much of the TE’s are selfish jumping DNA that cause disease when they land and disable genes or adversely affect them. But nature through shared interspecies TEs has supplied us with rock solid evidence for evolution because when they move they insert randomly and since we find thousands of them in identical homologous locations (called loci) in the genomes of different species, we have evidence for evolution that rises to the level of proof. Indeed, “macroevolution” level proof. These shared TEs must have inserted before then species split. And yes technically science rarely if ever proves - but evidence can be amassed to such a level that to deny a conclusion is perverse. Fortunately, most have lost the ability to move but for millions of years many did, leaving a record that can only be rationally explained by evolution. 1. LINE-1 Elements As with other retrotransposons when LINE elements land in genes they often disrupt them. A LINE-1 that is found in an exon (active part) of a gene called the APC gene, a tumor suppressor gene, together with other mutations inactivated the gene; it is not working in 80% of all human colon cancers. A canine tumor (CTVT) has a LINE-1 element inserted near an important proto-oncogene. LINE-1s insert like ERVs insert (2). Recall that retroelements copy and then randomly paste themselves back into the DNA. Of the approximately 600,000 LINE-1 elements in the human genome all but 2,000 are shared exactly with chimps and bonobos. As with ERVs, this means that over 99% of the LINE-1s in our genome have exact matches by location and ATCG sequences with chimps. Our genomes share all LINE-1 elements with gorillas except for 1,860. Some LINE-1 elements on rare occasions will grab a random RNA segment and then make a two-component element with the usual LINE-1 portion and an ‘innocent bystander RNA” (2). This results in a very unique LINE-1, a chimeric retrotransposon that have been found in human genomes and are especially solid evidence for evolution since they produce very unique shared markers also present between species; a common ancestor is the only rational conclusion. Not only can we find thousands of the same retrotransposons in the same genomic positions between species establishing evolution because they insert randomly and must have done so before the species split, but some are shared by some species and some not. If we collect hundreds and note which are shared between and which are not a pattern is produced that shows evolution in remarkable detail. Using molecular clock calculations we can also determine when the species split and compare those results to the paleontology (fossil) data. The data cries out evolution because there is so much of it across so many independent areas of science. In the case of DNA findings it rises to the level of proof of even macroevolution. Notice that this evidence for evolution is independent from function or not. More will be said about function. See Figure 1 below: Figure 1. Various LINE-1 insertions entered into the Primate Germ line, from their presence or absence in the genomes of primate species. LINE-1 elements: Open boxes. Chimeric inserts = grey boxes. Numbers indicate the number of individual inserts mapped. See text for discussion. From: Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. p 85. Figure 2.5. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. Paperback edition. 2. Alu Elements The origin of most retroelements have been lost in deep time. We do know however how Alus arose. Millions of years ago a gene called 7SL gene, important in signal recognition, fused to form a double DNA piece (called A and B sides) with a short section of an A-rich region between. It has an internal RNA promoter. Each Alu is unique in terms of accumulated mutations, the length, and the 3’ end. (3). Alus are only found in primates so we can determine evolutionarily about when primate evolution occurred. Of the 1.1 million Alus in the human genome, all but 7,000 are shared by chimps and bonobos. That again is greater than 99% shared Alus. Only a few thousand Alus in the human genome are not found in gorillas, establishing that Alus demonstrate the African great ape ancestor also had 99% of the Alu elements that humans, chimps and gorillas have. The only rational explanation is that these Alus must have copied and pasted back into the DNA in a common ancestor to the great apes. As in LINE-1s, some are shared by all primates and some by only some. By just collecting these raw observations one can produce an evolutionary phylogenetic tree demonstrating primate evolution, which most people would describe as “macroevolution” since it involves so many primate species, from macaques to humans. Out of the 1.1 million Alus found in humans, all are shared by orangutans except for 250, establishing a common ancestor between humans and orangutans. (2). Figure 2 shows an Alu insert into the HPRT gene found in multiple species including humans, chimps and gorillas but not other primates establishing evolutionary relationships. Notice the target site of [GAATGTTGTGA] where the insert happened and how the target site was duplicated and placed on either side of the changed DNA, confirming the insertion. Inactivation of this gene produces Lesch-Nyhan syndrome, a condition in children that produces gout, mental retardation, and self mutilation (2). Figure 2. The insertion of an Alu element in the HPRT gene. From: Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. p 90. Figure 2.7. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. Paperback edition. See text for discussion. Below in Figure 3 is the distribution of many Alu elements in various primate genomes. By simply noting which are shared by what groups an evolutionary phylogenetic tree is produced. This transposon evidence for evolution not only agrees with thousands of other DNA trees produced by shared ERVs, shared duplications, shared DNA breaks/repairs, and shared pseudogenes but also agrees with evolutionary trees produced by fossil observations (paleontology). Figure 3. Distribution of various Alu elements in primate genomes. Check marks and circles indicate presence and absence of particular inserts. Shading corresponds to the shading of the boxes and arrows, indicating when the Alu elements were added to the primate germ line. From: Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. p 91. Figure 2.9. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. Paperback edition. Are the insertions really random? Yes, they are. Turns out that LINE-1s and Alus do have some site preferences, but still not exact site insertion locations, or loci (4). Looking at any figures such as Figure 2, we can see that when they insert into a target site in the DNA, that area is duplicated on either side of the target, called Target Site Duplications (TSDs). Thus, we can find LINE-1s and Alus not only by their signatures but also by these TSDs. They are not original to the DNA. The idea that millions of TEs would randomly insert in the same exact genomic locations between species is mathematically impossible. What about hot spots? TEs do have preferences for insertions. They tend to insert around genes and also some prefer to insert into existing TEs. But these are preferences and not exclusive to the exact loci. As an analogy, there are car accident hot spots in cities where car accidents are more prone, but they are still accidents and each one is unique. Some cities have large numbers of people moving to them but they don’t all move onto the same street and certainly not into the same house. In neurofibromatosis type 1 the NF1 gene is mutated. “…of all the NF1 mutations, 0.4% are caused by retrotransposon insertions. In one study, 18 TE insertion mutations were identified in unrelated people, and six of these were clustered in a region of 1,500 bases. Three insertion sites were used twice…of the three sites that were targeted twice, all could be shown to be independent events… the TSDs were of different lengths, the initial cleavage events were on opposite strands of the DNA, or Alu elements of different sub-families were involved.”(2). In one study, 500 LINE-1 elements associated with the human genome were studied. In any other species did any LINE-1 element insert into any of those 500 sites? Not a single one. (2). Studies with Alu elements have also shown the same result. Human specific Alus were studied and “in no case was an Alu element characteristic of sub-families belonging to other species found in the same site as the human insert… It has been concluded that ‘no instances of insertion homoplasy in hominids have been recovered from the analysis of >2,500 recently inserted human Alu insertions’ (2). Exceptions: Incomplete Linkage Sorting It turns out that when comparing genomes there are many exceptions to the clustering of inserts into evolutionary phylogenetic trees. As an example, TEs have been found to be inserted into gorillas and humans but not chimps. Doesn’t this invalidate using TEs or other DNA changes as markers for evolution? Not at all. What is going on is called incomplete linkage sorting (ILS). Our genomes are made up of many different alleles, which are possible genes at a given location or locus. As an example, with the major blood group ABO, one can be OO, AO, BO, AB, AA or BB. Because we normally get one chromosome from each parent there are only two possible places for these specific multiple alleles. With the immune system for example there is an MHC complex where hundreds of possible alleles for a gene are available. Genes that have multiple possible alleles are called polymorphic. If speciation occurs rapidly relative to the time required for it to become fixed in a population (where all members have it), a new species may randomly lose a particular gene by chance and genetic drift when it splits off from the ancestor species. Anti-evolutionists made a big deal in 2012 after the gorilla genome was sequenced and it was found that up to 30% of the chimp, human and gorilla genomes showed incomplete linkage sorting (5). Considering that a particular critic of evolution is perhaps the leading creationist geneticist the attempt at obscuration and misrepresenting the findings was breathtaking. We’ve met Dr. Tomkins before in several other blogs on this site. See human chromosome 2 fusion , pseudogenes, and especially by Dr. Zach Hancock.  Dr. Tomkins is arguably the most prolific Young Earth Creationist writer in terms of genetics. It seems lost on anti-evolutionists that ILS is expected, noted and actually was predicted from population genetics by Kingman in 1982 (6). Instead of bad news for evolution this apparent anomaly in phylogenetic analysis actually supports evolution due to calculations, and the real apparent problem is why a top creationist apologist in genetics seems to have left his PhD back at his granting institution. For an explanation of ISL - it’s not easy to understand - see an article at The Panda’s Thumb and Freethought Blogs (7). One of the best insights possible into erroneous anti-evolution claims is drilling down on their arguments to expose fallacies, often committed by omission. Macroevolution deeper in time You may have noticed that the few examples I’ve extracted from Finlay’s book are primate centered. Perhaps you are wondering if these jumping TEs can be traced further back in time to show evolution earlier with even more distant shared common ancestors, like those evolutionary trees that scientists have produced through anatomy and fossils - a tree of life or more accurately a bush of life? And the answer is yes. Of course after millions of years TEs have become so degraded that there are limits. After the mouse genome was sequenced it was compared to our genome and studies showed there were large numbers of shared TEs. In particular LTR, LINE-1, LINE-2 and MIR (mammalian repeat) elements. “In a DNA segment encompassing 1 million DNA bases from the two species, 13 LINE-2 and 30 MIR elements were shown to be shared…inherited from the ancestor in which each element entered the DNA” (2). Finlay notes: “Computational searches have identified five TEs that are shared by primates and tree shrews, and in one case, by the flying lemur. These are all absent from rodents. On the one hand nine TEs were found to be shared by rodents and rabbits but are absent from primates. Primates, tree shrews, and flying lemurs form one monophyletic group; rodents, rabbits comprise another. But ultimately, we and the mice in the garden share many TEs each which arose in the genome of a Euarchontoglires [a clade and superorder of mammals that groups rodents, rabbits, primates and a few others based on TEs] ancestor” (2, pg. 105). Multi-species genomic comparisons have found several well-preserved TEs that corroborate shared ancestry in many species. One is an insertion site of a L1MB3 element. Humans share this TE with cows, horses, cats, dogs, bats and shrews. The degenerated undisturbed target site TACCTGGGAAACTTT is duplicated from the insertion on either side of the L1MB3 transposon (2). “As an illustrative example, an ancient MIR element in an intron of the beta-fibrinogen gene as been identified in the genomes of 22 species (Figure 4 below). The target site where the DNA was cut has the five base TTACT sequence. That sequence is retained in one of the target-site duplications of 8 species… and can be obtained by a one-base change in 18 other cases. We share this ancient TE with elephants” (2). Figure 4. Insertion of a MIR element in intron 7 of the beta-fibrinogen gene of various species demonstrating shared ancestry well beyond primate common ancestry. E - Euarchontoglires. L - Laurasiatheria. A - Afrotheria. From: Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. p 107. Figure 2.15. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. Paperback edition. A set of TEs was found to be shared by whales and hippos demonstrating that whales and hippos shared a common ancestor. Scientists moved whales into the order containing hippos, pigs, deer, sheep, cattle and giraffes based on this finding. Fossil whales were also found to have a special bone in their ankle confirming their artiodactyla ancestry. See my video on whale fossil evidence for evolution. A retrotransposon insertion in baleen whales led to the loss of enamel-capped teeth. See also a short video on DNA evidence for whale evolution. TEs show all living birds are monophyletic (2). Using shared TEs between genomes one can demonstrate evolution and clustering of species. We share common ancestors by shared TEs with elephants, sloths, armadillos and even birds and reptiles. We do live during a second Galileo moment for theology. Evolution, macroevolution, is true just as Darwin worked out 150+ years ago. The DNA evidence is sound, robust, and will withstand the best anti-evolutionists can bring to bear. TEs can be beneficial and functional Until this point the impression has been that TEs jumping around randomly damage a lot of genes and cause disease. They do, but they also have had many positive effects on genomes. Over long ages primate genomes have been invaded by millions of segments of LTRs, LINE-1s, Alus, and SVA elements. Mammals share genomic records of ancient invasions by LINE-2, LINE-3 and MIR retroelements (2). As Finlay points out TEs have provided DNA sequences for new genes. It is incorrect that evolution has not produced new genes and novel genetic information. By jumping in genomes they have also added to the variety of genes when they land into exons (the parts of genes that are left after splicing out the introns during processing the final gene mRNA). Lastly they have donated segments of DNA that have been co-opted by the host into regulatory networks (2). New gene examples include the BCYRN1 gene that is functional in nerve tissue. It was formed when an Alu was spliced into the genome of an ancestor to apes and monkeys. Another Alu element produced a family of genes eventually through a series of mutations to form an ASR element then into a CAS element and finally after two duplications into snaR genes. These are transcribed into small RNA regulatory molecules that probably regulate protein synthesis (2). The PMCHL1 and PMCHL2 genes were assembled from genetic parts, one of which was an Alu element. Besides the Alu element, the genes include several downstream exons and a gene duplication. These genes are active in the testes, fetal brain and encode non-coding RNA transcripts (2). Several Alu elements were used to form the FLJ33706 gene that was spliced into the primate germ-line line and later provided a protein-coding sequence (2). TEs also have provided DNA material for new exons. As mentioned, when the DNA is read to make a final mRNA product that will go to the ribosomes to make proteins, it must first be processed. Most of the transcription is DNA that is nearly always thrown away as introns, leaving only the exons to be spliced together. In the human genome TEs have contributed repeatedly as novel exons. TEs occur in 4.4% of all transcripts and in 0.5% of all DNA sequences that code for proteins. A survey of 330 Alu-derived exons has shown that most are minor components of gene output (2). TEs have also assumed many regulatory roles. An analysis of eutherian genomes showed at least 16% of all the studied conserved non-coding elements were shown to be formed either wholly or in part by TEs representing multiple families including ERVs, LINE elements, MIR elements and DNA transposons. Non-coding genes produce RNA products for regulation instead of protein products. It appears that "6% of all TEs have acquired stable functions as shown by the fact that they contain sequence motifs that resist change.” (2). Many transcripts in human tissues are initiated from specific sites within TEs and include some fibroblasts, liver, brain and 16% of embryos. As discussed extensively in another blog about ERVs at this web site regarding retroviruses and the fossilized ERVs they produced, the LTRs present in ERVs have been repeatedly co-oped to be used by the host as promoters for DNA transcription. About 90% of the ERVs in our genome consist only of LTRs, which are functional and 8% of our genome are made of ERVs. About 10% of ERVs have all three genes that hark back to their parasitic infectious origin. Importantly, most jumping genes either land in areas that cause no damage or have caused few problems. Sometimes two TEs of the same class can join, deleting the DNA between them producing a single chimeric TE (2). "On short timescales, recombination events, leading to the loss of intervening sequences, cause genetic damage. But on evolutionary timescales, the same processes reorganize genome content, contributing to the transformation of the genome of progenitor species into those of descendent species.” After humans split off from our shared chimp ancestor, more than 70 recombination events occurred between LINE-1 elements resulting in the loss of 450,000 bases… and more than 490 recombination events occurred between Alu elements also and these excised another 400,000 bases from the human genome.”(2). One gene, SIGLEC13, is present in chimps and Old World Monkeys, accompanied by several Alu elements, but the gene is absent in humans. During our evolution “the entire gene was neatly excised by a recombination event between the left-handmost Alu element and the Alu element just to the right of the last exon.” (2). Our genome contains many repeated units. If the basic repeat unit is very short, such as only three bases as in -AAG-, the repeat is called a microsatellite. Repeated sequences are often found within LINE-1s and Alu elements. “Microsatellites tend to have high mutation rates… They underlie some 40 genetic diseases…The ability of TEs to introduce such sequences into genomes destabilizes them”. Myotonic dystrophy type 2 developed from an Alu element that appeared in our ancestor and stimulated many repeats perturbing gene function and leading to a genetic disease (2). Host genetic systems do have ways to suppress jumping through epigenetic tags like methyl or acetyl groups. “Organisms possess regulatory mechanisms to suppress the insertional mutagenesis associated with TE activity. However, such genomic stability may be incompatible with adaptive change over the long term. A high mutational burden is disadvantageous to individuals, but promotes variation upon which natural selection can work, and hence promotes the development of adaptations… Patterns of long-term stability interspersed by bursts of active speciation [by waves of Alu insertions into primate genomes] are well recognized and have been called punctuated equilibrium “ (2, pg. 129). Conclusion This discussion of transposable elements (TEs) has been more technical and longer than wished for. Sometimes when it comes to science, brevity is sacrificed for accuracy. Three major types of retrotransposon TEs were discussed: ERVs, LINE-1s, and Alu elements. These three types are examples of non-DNA jumping genes and together constitute 36% of our genome alone. They are called TEs because they can or have in the past jumped around randomly in genomes. Although they have insertional preferences, they insert randomly by specific location (locus). TEs that are shared exactly between species constitute spectacular evidence for evolution, specifically macroevolution. Shared ERVs were discussed in a separate composition about how they are derived from random viral insertions and essentially rise to the level of proof of common ancestry. Why anti-evolution objections fail is also addressed. The two LTRs at the ends of the provirus have in most cases swung around in the distant past during recombination events producing solo LTRs. Most ERVs are only LTRs now and make up an astounding 8% of our genome. Shared LINE-1s and Alu elements between species were discussed in this entry as amazing evidence for evolution also because they also insert randomly and produce nested trees of linked ancestry. Three important takeaways need to be emphasized. First, TEs insert randomly and we find over 50% of our genome is TE derived. So many unique TEs are shared by other species in the exact same locations often with the same mutations, that the only rational conclusion is species that share the same TEs must have shared a common ancestor in the past. Shared TEs indicate insertions before the compared species split. Like the same scratches on two different rifle bullets must have come from the same rifle (origin) and are admissible in a court of law, so also shared TE’s constitute proof of a shared biological origin since they insert randomly. So much for genomes being like blue-prints and unchanging! Secondly, the millions of TEs can be nested in evolutionary phylogenetic trees. Some are shared by species being compared and some are not. If we combine them into groups, nested phylogenetic trees are produced and multiple independent trees all rationally point to only one conclusion: macroevolution even going deep in time is a fact. This disproves attempts to explain TEs as a result of a “Fall” since any disease or breaks in the DNA introduced at a proposed "Fall" would not produce nested evolutionary trees. Third, this jumping is independent of function. Many TEs are functional but the vast majority are not. Most of the time the jumps and new inserts are neutral or cause damage and disease through disabling genes. Over millions of years the host has evolved means to suppress them (methylation and acetylation, e.g.). "Sometimes they jump into very important spots, either genes themselves or in areas of the genome that is important for regulating genes... Joshua-Tor and Ipsaro examined a mouse protein called Asterix/Gtsf1 that immobilizes LTRs" (8). The host as also co-opted many for the host’s own use (especially LTRs which act as promoters and enhancers). To repeat, if TEs were mostly functional or none were, functionality would not matter. It’s the random inserts and the fact that they share the same TEs at the same locations between species that establishes evolution and common ancestry. The topic of functionality is not applicable to the observation of them being randomly inserted and shared between species. This sharing of TEs, producing hundreds of independent phylogenic trees that reach into the deep past, is what also proves macroevolution. A theological and historical appeal to a “Fall” becomes what it always was - a mythological solution to natural observations that only appears on the surface to be explanatory. It was destined to be displaced by science and exposed as fantasy; a literal belief unfortunately that persists and is accepted by billions of people on our planet still. This is the fifth and final article on this site based on a simple principle - the observation that shared random DNA changes between species can only be rationally explained by evolution and common ancestry. It is suggested if possible that readers just read Finlay’s book that these articles are based on. Only a few examples from his book can be showcased in these articles. The previous four associated articles are ERVs, DNA repairs/patches, segmental duplications and pseudogenes. A proper examination of how we actually observe DNA in compared genomes cries out evolution, and even “macroevolution”. People need only look inward to their bodies for definitive evidence for evolution in themselves. It was there all the time. To help emphasize the simple principle of shared random DNA markers between species and how they can only be explained by evolution, an organizing post with links to all DNA five articles was produced. In order to counter anti-evolution false objections many of the articles contain answers to common proposed objections. That made the articles longer to be more complete. Even those who accept evolution may not know how strong the evidence from DNA is for “macroevolution” and are encouraged to consider reading those contra-apologetic sections. Some may have realized that all this jumping within genomes would also produce junk DNA. That is a controversial topic unfortunately in biology with even non-religious scientists thinking we have little to no junk DNA. On the contrary, here is an entry arguing junk DNA ?  for the opposite situation and based on sound genomic principles. References and Citations 1. Transposons: The Jumping Genes https://www.nature.com/scitable/topicpage/transposons-the-jumping-genes-518/ 2. Finlay, Graeme. 2021. Human Evolution: Genes, Genealogies and Phylogenies. Cambridge University Press. 359 pp. Paperback edition.  ISBN 978-1-009-00525-8. 3. Alu elements: know the SINEs https://rdcu.be/drIPT 4. Levin, H.L. and Moran, J.V. 2011. Dynamic interactions between transposable elements and their hosts. Nature Reviews Genetics 12: 615-27. 5. Gorilla Genome Is Bad News for Evolution https://www.icr.org/article/gorilla-genome-bad-news-for-evolution 6. Understanding Incomplete Linkage Sorting. https://www.reddit.com/r/evolution/comments/2w42at/understanding_incomplete_lineage_sorting/# 7. A Tiny Bit of Knowledge is a Dangerous Thing https://freethoughtblogs.com/pharyngula/2012/03/11/a-tiny-bit-of-knowledge-is-a-dangerous-thing/ 8. How to Tame a Restless Genome (protein shuts down LTR-transposons) https://www.sciencedaily.com/releases/2021/04/210408131411.htm I think he's wearing blue genes while he jumps........

"DNA breaks are random and potentially catastrophic. The molecular details... are yielding to stringent molecular analysis, which have revealed that the telltale messiness of the repair patch is inherent to the repair system. Random breaks are fixed by the desperate co-option of any available DNA... Such patches are sufficient evidence of great ape monophylicity." ~ Graeme Finlay. Introduction As many people know, DNA is the molecule of life that holds instructions for maintaining, growing and starting new life. Some forms like occasional viruses use RNA instead of DNA, so perhaps it is more accurate to say strings of nucleic acids are responsible for life. Most organisms we are interested in use DNA however. DNA is not actually like a blueprint because it is constantly changed and modified through recombination, deletions, insertions, and mutations. Many of these modifications can cause damage and they need to be repaired as quickly as possible to keep the instructions and directions for life intact. DNA is actually fragile. Fortunately, cells have various mechanisms for detecting and repairing double stranded breaks in DNA. As Finlay discusses in his book (see full citation and acknowledgment at the end of this article), broken DNA ends are often stitched back together using whatever pieces of DNA that are close at hand, more like a Band-Aid patch. This “repair-or-die” as he calls it sets up an emergency repair that is unique because not only is the break random but so is the repair patch, producing a unique signature or DNA scar. It leaves a unique mark on that section of DNA where it was repaired with a section of DNA that will vary by unique ATCG letter sequences. These patch fixes represent types of repaired errors or scars. Scientists studying genomes have found many of these previous scars and we can compare them between species. If these DNA repair scars are found between species in the same chromosomal locations with the same piece of DNA that was grabbed and inserted to glue the broken DNA ends together, we can be certain that the only rational explanation is the two species at one time shared a common ancestor. It is as if an authentic artist's signature is found on two paintings, we can be sure they had the same person painting them. These repair scars then are powerful evidence for common ancestry. This results in a test of evolution because the pattern of inheritance of the same random damaged and randomly repaired DNA sections across species should reveal shared ancestry and common descent. Phylogenetic trees result showing evolution and conclusive common ancestry. And the tree from DNA repairs can be compared to phylogenetic trees from other independent fields of science. NHEJ Repairs The acronym NHEJ stands for non-homologous end-joining . If the break and repair occurs in a sex cell it will be passed down through the generations. Scientists can find these repairs by noting sections of matching DNA copied from one site to another with losses and gains of DNA bases at the recipient site. According to the cell biologist and cancer researcher Finlay, hundreds of such emergency repair jobs have been found in genomes of various apes, including humans. See Figure 1 below of an actual DNA repair patch. "Non-templated" refers to bases added but not copied from a DNA strand. Figure 1. DNA repair. From: Finlay, Graeme. 2013. Human Evolution: Genes, Genealogies and Phylogenies. p 140. Figure 3.3. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. Finlay's explanation: “The original, undisturbed sequence in the macaque genome is shown. However, in humans and chimps this sequence is disrupted, and an extensive length of foreign DNA (starting ATCTT…) has been imported to join the ends. Six randomly inserted filler bases (GCTTCC) are present on the left-hand side of the break, and two bases (GC) have been deleted from the right-hand side. This example provides compelling evidence that humans and chimps share a common ancestor. Moreover, 36 other examples of shared repair patches linking humans to chimps to a common ancestor have also been found.” [p. 140]. See above diagram of the DNA findings. As Finlay points out, hundreds of DNA repair scars have been found. Some are shared between only some species. For example, 142 are shared by orangutans, humans and chimps only. Others are shared by all great apes, old world monkeys, and new world monkeys (389). Some even are shared across large groups (22). Thus, just by tabulating which repairs are shared and which are not, evolution is demonstrated. “These represent a relatively well-preserved selection of sites that have survived vast tracts of time since the Euarchontoglires and Boreoeutheria ancestors lived… The distribution of shared repair patches generates a phylogenetic tree that is congruent with that generated from ERV and retrotransposon insertions. NEHEJ and retrotransposition are wholly independent processes…” .(Finlay) See Figure 2 below of shared DNA findings producing an evolutionary phylogenic tree. Figure 2. Identical DNA repairs compared between species. They nest in a hierarchal pattern demonstrating shared ancestry. OWM = Old World Monkeys. NWM = New World Monkeys. From: Finlay, Graeme. 2013. Human Evolution: genes, genealogies and phylogenies. p 140. Figure 3.3. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. Numts Repairs As has been discussed, these DNA breaks are random and the repairs involve grabbing random DNA copies or pieces nearby for the repair. Sometimes that is a section of native DNA that is copied. Other times random nucleotides are inserted (what are called “non-templated” DNA in Figure 1 above). Still other times the cell will even grab old parasitic fossilized viral DNA from transposons such as LINE-1s. An additional surprising source even has been found to be mitochondrial DNA. As you may remember mitochondria were originally free living bacteria that evolved into our ATP power generating organelles through endosymbiotic capture and they have their own bacterial DNA. (see Moms and Mitochondria, this site) It turns out that sections of mitochondrial DNA are found in nuclear genomes of nearly all organisms from fungi to animals according to Finlay. How did mitochondrial DNA get into host cell nuclear DNA? Because when some cellular DNA was repaired the repair involved grabbing DNA as a patch and the DNA close by was from mitochondrial DNA. These repair patches have their own designation, nuclear sequences of mitochondrial origin or numts, also called mitochondrial pseudogenes because they are non-coding mitochondrial genes that have been inserted into host nuclear DNA. (Finlay) The number of human numts found averages about 600, depending on the criteria used. Some are found in only humans. Others have been shown to date from early ape-monkey history (Finlay). If grouped by shared occurrence this produces a phylogenetic tree that matches those phylogenic trees independently produced by shared ERVs, LTRs, and fossils (see Shared ERVs and evolution, this site), and of course the NHEJ repair scars discussed in Figure 2. See Table from Finlay: Table 1. Listing of some numts shared by various groups and also across species. Numts refers to random DNA patches/repairs using nearby pieces of mitochondrial DNA. From: Finlay, Graeme. 2013. Human Evolution: genes, genealogies and phylogenies. p 141. Table 3.1. Cambridge University Press. Social sharing and Fair dealing applied per publisher's web instructions. As Finlay writes, “Whole-genome surveys have indicated that most of the numts in our genome, 502 (that is over 80%) are present also in the chimp genome… But analysis of the presence and absence of individual numts in multiple primate genomes…. have shown that humans, chimps and gorillas are monophyletic [we and they share a common ancestor]. So are the great apes (incorporating the orangutans) and further back in time, the apes (incorporating the lesser apes and gibbons). It appears the majority of numts in our genome are shared with old world monkeys”. “Are numts functional today? Quite possibly - but functionality is irrelevant to the issue whether numts constitute markers of descent. It is the complex molecular pathway by which numts arose that makes them such compelling signatures of our shared ancestry with other primates.” Conclusion The DNA molecule is fragile and easily broken. Because of its importance to heredity and the function of the cell, breaks must be repaired quickly. This repair produces a DNA patch or scar that can be identified and studied across species. The breaks are random and also is the DNA patch material. Thus, when we find the same breaks in some species with the same patch material we can be certain the only rational explanation is common descent or evolution from common ancestors. To further solidify this conclusion different repaired patches can be grouped across species into a phylogenetic tree that not only confirms evolution but replicates the same evolutionary conclusion using other independent lines of scientific inquiry and phylogenic trees. Newer DNA evidence such as the same DNA repair scars across species points to the same conclusion - evolution is true. This is another example, as is shared ERVs discussed on this site, that specific DNA findings support evolution in a spectacular way. The approach with DNA scars is similar to how we can use random retroviral inserts to show common ancestry via shared endogenous retroviral (ERV) findings. Acknowledgement I am grateful for the effort and time Dr. Finlay took to write an excellent review of newer DNA findings that dramatically confirm human evolution. His writing style is clear to the non-scientist and his conclusions supported by copious examples. As a theist, he should also be regarded as above reproach in terms of motivations. Highly recommended. The subject of DNA scars and the writing in this article are based solely on his book and not original to this author. Finlay, Graeme. 2013. Human Evolution: Genes, Genealogies and Phylogenies. Cambridge University Press. 359 pp. 283 pp. not including References and Index. Paperback edition. 2021 - ISBN 978-1-009-00525-8 Social sharing and Fair dealing applied per publisher's web instructions.

"As soon as you begin to look at our bodies from an evolutionary perspective you see more and more we are not intelligently designed." ~ Paul Sherman, PhD Much of the evidence for evolution takes time and interest to learn. How we know evolution is true comes from many independent areas of science including genetics, paleontology, geology, biogeography, developmental biology and many more. Evidence from our own bodies is easier to access and understand for many. After presenting some fairly simple observations about our own anatomy to a high school biology class that is best explained by evolution, it became clear that others may find these observations interesting also. It's 36 minutes long and a fun way to look at how our past evolution has produced some amazing and often hilarious work-arounds to solve issues that came up during our development as a species. Many of these examples can be found in my blog entry on Unintelligent Design. For more convincing evidence for evolution that presents similar visual evidence especially see the videos on whale evolution. For evolution evidence that rises to the level of near proof, see the blogs and section entries discussing the DNA evidence for evolution, macroevolution.

What do women have in common with termites and carpenter ants? "We are not made up, as we had always supposed, of successively enriched packets of our own parts. We are shared, rented, occupied. At the interior of our cells, driving them, providing the oxidative energy that sends us out for the improvement of each shining day, are the mitochondria, and in a strict sense they are not ours." ~ Lewis Thomas "Over the long term, symbiosis is more useful than parasitism. More fun, too. Ask any mitochondria." ~ Larry Wall Introduction When examining how we know that evolution is true many people may not realize that evidence is abundant within us. It’s not just evidence from the fossil record. Several examples were detailed in my post on unintelligent design, and how our DNA also greatly supports human evolution is discussed in the sections on shared ERVs and human chromosome 2 fusion. As you may remember from biology, we need to replace millions of cells per day. When a cell divides it produces a new cell and passes its instructions to the daughter cell by duplicating the DNA instructions in its nucleus before dividing. These instructions will be used to make the organelles in the new cell such as the Gogli apparatus, cell membrane, vacuoles, nucleus, lysosomes, etc. There is one organelle however that is not made this way. It actually has it’s own DNA, different from the nuclear DNA. These are the mitochondria of nearly all eukaryotic cells. Also known as the powerhouses of the cells, they produce the ATP that is used to supply the energy currency to just about everything the cell does. Some cells, like red blood cells, do not have any to save space for carrying oxygen by hemoglobin whereas other cells like muscle cells have thousands per cell. A few eukaryotes are lacking mitochondria. They obtain their energy through anaerobic pathways - reactions that don’t use oxygen. Examples include intestinal parasites such as Giardia lambda, Entamoeba histolytica and Trichomans tenax. It is unclear if they lost their mitochondria or if they are descendants before mitochondria were acquired (1). More on this in the next section. How We Know Mitochondria Previously Were Bacteria As biologists studied these organelles, they noted that unlike all the other cellular organelles, they were unique. They were about the size of bacteria. They have two distinct membranes. The deep folds on the inner mitochondrial membrane resemble the folds called mesosomes found in prokaryotic cells like bacteria. Mitochondria have their own DNA, only 37 genes, and the DNA is in a circular form like bacteria, unlike the cell’s DNA in the membrane nucleus (2). The mitochondrial genes are very similar to bacterial genes like those found in Rickettsia. Of their 1,000 proteins, 40% of the mitochondria are bacterial. When they reproduce they do so by fission end to end like bacteria do instead of being made by the cell. They have unique ribosomes, the structures that assemble amino acids to make proteins. Lastly, they can be affected by antibiotics, which are used to control or eliminate bacterial infections. All of these characteristics and the DNA findings especially eventually convinced scientists that mitochondria were once free living bacteria that were captured somehow by our very distant past ancestors. How scientists were finally convinced involves a researcher named Lynn Margulis and that is also an interesting story itself. This theory, that mitochondria were once free living bacteria that came to set up shop and become adapted in eukaryotic cells, is called the endosymbiotic or symbiogenesis theory and is credited to her. Fossil evidence supports that this swallowing of a bacteria by another prokaryote without killing it probably happened about 2.4 billion years, giving rise eventually to the present condition of mitochondria powering eukaryotic cells (3). A similar capture probably occurred with chloroplasts in plants since they have the same bacterial characteristics discussed above and closely match cyanobacteria. Termites, Carpenter Ants, Moms, and Mitochondria It turns out termites and carpenter ants that eat wood for food (xylophagia) actually cannot digest wood themselves (4). Although there is one group of termite species that do have the ability to make cellulase, many cannot. These species must use gut bacteria to do it for them. Just like we can’t make vitamin K but rely on our gut bacteria to do it for us since our diets don’t supply enough. In the case of these wood eating insects, the adults pass the needed bacteria orally to newborn offspring to establish the gut bacteria they will need to digest and live off wood as food. In humans, we only inherit mitochondria from our mothers. She passes on all the mitochondria we will inherit and must do this since we depend on mitochondria to reproduce themselves. Any paternal mitochondria that the sperm carries into the egg at fertilization is destroyed by the maternal egg enzymes, and some studies show the paternal mitochondria of the sperm may also auto-destruct after the sperm enters the egg (6). So like termites and carpenter ants, we are dependent on our mothers when it comes to having bacteria in order to live. Our mothers must “seed” our original zygote cell with former bacteria in order for us to survive. How could it have happened? A recent study shows how phagocytosis (engulfing to eat) in one or more single celled organisms experienced eventually may have led to endosymbiosis. https://www.quantamagazine.org/ancient-genes-for-symbiosis-hint-at-mitochondrias-origins-20220426/ Conclusion The origin of mitochondria is another story that is best understood from evolution (5). This theory is most commonly known as the endosymbiotic theory for mitochondria and chloroplast origins. This is another example of how understanding evolution gives us a “why” of life. Evolution is vital even to medicine since we can now understand why mitochondrial diseases are only passed from mother to child and not from the father. Evolution is vital for a complete understanding in medicine. This topic is discussed further at my blog on Evolutionary Medicine. Addendum (4/2023) - New forms of cellular symbiosis found consistent with endosymbiosis. A new form of symbiosis has been discovered. A bacterium supplies unicellular ciliates with energy, but from nitrogen. The bacterium has not co-evolved long enough to loose its independence like what happened with mitochondria. https://www.mpg.de/16524858/new-form-of-symbiosis-discovered Single celled alga found with evidence of seven different organisms living inside it. https://www.newscientist.com/article/2371017-evolutionary-oddball-has-seven-genomes-inside-a-single-cell/ Citations 1. https://sciencing.com/characteristics-mitochondria-12765.html 2. https://www.britannica.com/science/mitochondrion 3. https://www.pbs.org/video/how-two-microbes-changed-history-mnwo8g/ 4. https://www.biointeractive.org/classroom-resources/termites-digest-wood-thanks-microbes 5. https://www.nature.com/scitable/topicpage/the-origin-of-mitochondria-14232356/ 6. https://www.nytimes.com/2016/06/24/science/mitochondrial-dna-mothers.html

How vs. What: why it’s important in evolution discussions “Ignorance more frequently begets confidence than does knowledge: it is those who know little, not those who know much, who so positively assert that this or that problem will never be solved by science.” ~ Charles Darwin. The Decent of Man “Evolution is a theory, and it’s a theory that you can test. We’ve tested evolution in many ways. You can’t present good evidence that says evolution is not a fact.” ~ Bill Nye Introduction When a committed anti-evolutionist views the three whale evolution videos I produced, the evidence for whale evolution is so overwhelming that often a very predictable response occurs. Rather than address the evidence and why we know whales evolved, the person pivots and attempts to divert to what I call the “whataboutthisthen?” response. What usually follows is a listing of many of the amazing adaptations of cetaceans with the accompanying challenge of how could all of this have come about naturally? But the “what” comes before the “how” in nearly all investigations and this attempt is what is called putting the cart before the horse. This “butwhataboutthisthen” also can happen when discussing the DNA evidence for evolution, as detailed in my site discussions of shared ERVs, human chromosome 2 fusion, shared DNA repairs, and pseudogenes - but to a lesser extent. Shared ERV objections for example often start by trying to show that retroviral insertions are not random or that the LTRs are original and not a result of past retroviral insertions. Or, since no one saw the HC 2 fusion, the evidence for it is dismissed. Having failed to discount the incredible DNA evidence for human evolution, the anti-evolutionist will often then appeal to the amazing complexity of 3 billion human DNA nucleotides (the “steps” of the DNA “ladder”) and run the Intelligent Design flag argument up the flagpole. Given the complexity, they ask how could the DNA have evolved by only natural means? Or, give up completely and move directly to abiogenesis, which has no direct involvement with evolution (see abiogenesis). Thus the mound of evolutionary evidence “what” we observe is completely bypassed as if it magically is not central to the discussion. The origin of species is a different topic from the origin of life. Appealing to gaps in knowledge and holding them up as evidence is not evidence. By ignoring the evolutionary evidence and diverting to “hows” and abiogenesis, the attempt is made to avoid addressing the overwhelming facts that support evolution. This avoidance of evidence, of what we do know, and pivoting to demanding to know how something occurred first, usually also includes wanting to know to their level of satisfaction. Experts and specialists in various scientific fields are simply dismissed. But must we always know how something happened before we accept that it DID happen? Absolutely not! Yes, to fully understand something it is important to know the “how” and we strive for that. Scientists are constantly working on how something came about, to close those unknown loops. But our curiosity starts with just observations, the plain facts or proposed hypotheses to test. In Hollywood, scientists are often portrayed as shouting “eureka” upon making a discovery, but rather most often it’s a phrase quietly uttered, “well, that’s funny” or, “well, that’s interesting” and then the search for how the observation could be explained is on. In the following section I will present multiple examples of why we put the “what” before the “how” and more importantly that the observations can often stand alone as a conclusion without knowing how something occurred. These two questions are thus separate and we can know that the “what” is true and practical without knowing the “how”. I have not in general discussed how whales evolved nor the mechanisms that produce evolution. We must begin at the beginning - observations or tested hypotheses and knowing evolution is true because of what we know before proceeding to investigating how species arise. Ignoring observations is a diversion from addressing the fact of evolution. Mechanisms are not unimportant, but they in nearly all cases follow observations and hypothesis testing first. I will list several examples of why knowing the “what” is independent of the “how” because in my experience this attempt to discount evolution evidence by demanding exactly how something happened, usually to their satisfaction, is an excuse and false justification for rejecting sound and robust evidence for evolution. This method of avoiding the obvious is a very insightful demonstration that the rejection of evidence for evolution is usually rooted in presuppositions and an allegiance to anti-evolution views at any cost. Throwing out the “butwhataboutthisthen” is a type of cognitive dissonance avoidance defense mechanism and attempt to divert the discussion from the facts before them rather than a sincere question. Examples 1. Aspirin. It’s pain relief and anti-inflammatory properties were known for 4,000 years. Humans derived its main ingredient, salicylic acid, from various tree bark species, including the willow tree. Our ancestors knew what it was useful for without knowing how it worked. In 1971 scientists noted how aspirin operated by blocking prostaglandins. In 1976 researchers discovered how aspirin further worked by binding to the specific enzyme cyclooxygenase, (COX), and lowering prostaglandins. For 4,000 years we acknowledged what aspirin was good for and used it without knowing the how. 2. Court cases. Many murder convictions around the world have occurred even though a body was not recovered and sometimes not even the murder weapon. In 2000, Gregory Chrysler and Lawrence Weygant were convicted of murder by beating a coworker to death even though the body and bat were never found (July 2000 Times-Herald Record). Unwitnessed, and the “how” evidence was never found. Enough other evidence can be presented to show an event must have happened in the past. In court cases, this can include DNA forensic evidence, phone records and GPS information, etc. The how is not necessary to reach a solid conclusion of what must have happened. We can be certain whales and humans evolved by the massive amount of confirming evidence and the consilience of that evidence. The how is not critical but we’d like to have that also. DNA paternity testing as evidence alone is 99% certain even though where, when and how the conception occurred may not be known. IVF? Consensual? Rape? Hotel room or at home? Time of day? It is not necessary to confirm paternity or rule out candidates to know all the aspects of how the conception occurred to answer the biology question. Legal and moral questions may need the "how" inputs however. 3. Sun rises in the east. For thousands of years people knew the sun rises to our eyes always in the east. They could predict it and navigate by the stars without knowing how the sun and stars formed and why the sun appears in the east to us. 4. Driving a car. Most people drive their cars without knowing how all the specific systems work. They know what a car is without knowing how it all works. With an internal combustion engine, it is not necessary to know how each system in the car engine works in order to drive and use the car (coolant, gas/air combustion mechanics, air conditioning, etc.) How many of us can describe in detail how an automatic transmission actually works? Does that stop us from using cars? If the exact "how" something evolved in all it’s steps is not completely worked out, does that mean we are justified in not accepting that it did evolve if the evidence is compelling and massive that evolution must have taken place? 5. The vacation cabin. After many months, you return to your wonderful vacation cabin only to find it destroyed. Only the chimney is left standing. Debris is everywhere. No witnesses are available. The fact that your cabin, or what is left of it, is in shambles cannot be denied. But how did it happen? Hurricane? Tornado? Forest Fire? Earthquake? Mad neighbor? Gas explosion? Those possibilities will be investigated, especially by the insurance company, but does the how in any way change the fact that it has been destroyed? Do you withhold a conclusion of total destruction for months or years of denial awaiting a final “how”? What if it is never concluded exactly how it was destroyed? Does that change the fact that it is no longer there? Are we to dismiss the overwhelming evidence that whales evolved or the incredible DNA evidence that humans have evolved because someone is dissatisfied with the explanations of how it happened? 6. Building fire. Recently (2023) a large apartment fire occurred in a nearby town close to me. It started on the fourth floor and since it was an old building, the building was a total loss. No one died but two fire fighters were injured. As we watched the building on fire and the roof caving in on the news, they noted that no one knew how the fire started. Electrical? Candles? Smoking? Does how the fire started in any way impact on the fact that the building was on fire and ultimately destroyed? 7. Caffeine. The scientific name is 1,3,7-trimethylxanthine. First discovered in China around 1000 BC in the form of tea it was later discovered as coffee in Ethiopia around 850 AD. This is the most widely used drug in the world for thousands of years but was it necessary to know how it worked for people to use it as a stimulant? It wasn’t until the 20th century that researchers determined that caffeine works by attaching to the body’s A1 adenosine receptors, not allowing adenosine to act to make you sleepy. This in turn raises your dopamine and glutamate levels and you feel more energetic. Did not knowing the exact biochemical mechanism, the detailed how, in any way keep people from using caffeine for thousands of years, of knowing that it was useful and what to use it for? 8. Cholera. The disease cholera has been with humans for hundreds of years. There have been numerous outbreaks and several pandemics. It may infect up to 4 million people per year and may kill up to 140,000 people per year through copious diarrhea and dehydration. One of the pandemics reached London in 1854 and John Snow mapped cases in the Soho part of the city demonstrating hot spots in that area. He had the water pump handle removed with the immediate result of a decrease in cases. In 1883 the causative bacteria was finally identified to western science. It would be over a hundred years before the exact mechanism for how the bacterial toxin causes the severe diarrhea was revealed. The toxin activates through ADP a cellular signaling GTP protein. This causes CTA1 loop changes that allow NAD+ to bind to the active site and causes electrolyte shifts and ultimately death in some cases. Was it necessary to know all the details of how cholera, through its toxin, causes disease and sometimes death in order to know that the etiology was a bacterial species and its toxin? Could we use basic observations that the cause wasVibrio cholerae without knowing exactly how it produced disease? Knowing how it causes disease can help in designing drugs and treatment but does it change the fact of the causative agent? Does demanding to know exactly how whales and humans evolved change all the evidence that we have showing evolution did happen? Is it justified to withhold agreement that evolution in these two examples happened because every possible step in how it occurred may not be available yet ? https://www.history.com/topics/inventions/history-of-cholera https://www.science.org/doi/10.1126/science.1113398 How vs. What and Einstein? Scientist : Einstein's theory of general relativity has been validated and corroborated by evidence. Critic : Einstein's theory of relativity cannot be valid until you explain the origin of space-time. Scientist : Listen, there is evidence for this theory, let's talk about that. Critic : If you cannot explain the origin of space-time, your theory is false, because where did the space-time needed by general relativity come from ? It's a religion because you can't explain the origin of space-time ~Adeleke Emmanuel Oluwasegun Conclusion When examining the overwhelming evidence that evolution must be true, how it happened is an important secondary question, but it is not critical and does not carry the force of disproving evolution. Actual and theoretical examples were discussed showing that how is not critical to reaching a solid conclusion and even practical considerations in many cases. An appeal by someone that they will not accept the evidence for evolution until they know exactly how it happened is really an avoidance maneuver, and rarely sincere in my experience. It is a red herring. Wanting to know how evolution unfolded can be a sincere inquiry and centers around how new information for natural selection to operate on becomes available. Those sources are known and found by a search of the literature. There will always be unknowns in science - it’s one reason for scientific activity. Not knowing everything does not mean science does not know enough to make sound conclusions regarding observations and revealed insights through experimentation. We don’t need to have perfect knowledge to have secure knowledge and reach sound conclusions. How and why are often what drives our curiosity but it usually starts by noticing observations and data. Those must be acknowledged first. Evolution is true not only because it fits observations but because it passes testing and makes verifiable predictions. How it occurred, the pace, and other considerations are still areas of active research and debate but the fact of evolution is settled science.

“Seen in the light of evolution, biology is, perhaps, intellectually the most satisfying and inspiring science. Without that light it becomes a pile of sundry facts -- some of them interesting or curious but making no meaningful picture as a whole.” ~ Theodosius G. Dobzhansky “What counts is not what sounds plausible, not what we would like to believe, not what one or two witnesses claim, but only what is supported by hard evidence rigorously and skeptically examined. Extraordinary claims require extraordinary evidence” ~ Carl Sagan “The evidence supporting the idea that all living things are descended from a common ancestor is truly overwhelming. I would not necessarily wish that to be so, as a Bible-believing Christian. But it is so. It does not serve faith well to try and deny that.” ~ Francis Collins, MD, PhD. Former Director of the National Institutes of Health (NIH). Former Leader of the Human Genome Project (HGP). Aug. 2006, BeliefNet.com Evangelical Christian, Founder of Biologos I am usually surprised when people tell me they have no problems accepting Evolution - the theory that all life on this planet has evolved from very simple forms, it’s all related (we share genes with yeast) and probably life emerged from non living precursors. Life is so complicated and the more we learn the more unimaginably complex it is. How could all of this life have arrived through natural processes only? Is it no wonder that even the non-religious will often view life as intelligently designed, usually because they don’t know of all the unintelligent designs that can only best be explained by evolution and work-arounds by natural selection? I find that the above quote by Sagan also applies to Evolution. This scientific theory is so extraordinary, so radical, so counter intuitive for most, and touches so many aspects of our lives that we should demand robust and incredible evidence for it. That evidence is available and comes from fossils, genetics, biogeography, anthropology, comparative anatomy, paleobiology, developmental biology, and so much more. Equally important, the evidence is often the result of confirmed predictions, the evidence that would disprove evolution such as fossils out of sequence never occurs, the theory has been rigorously tested for over 150 years (want to get 1 million dollars and a Nobel? Show that it is wrong) and the evidence comes from independent fields of science demonstrating consilience. I assert that evolution is not intuitive for most. A pilot must be taught to accept their instruments when flying in poor visibility instead of what they may feel but is dangerously wrong. We must reject our feeling that we are not moving in spite of knowing the earth is spinning at 1,000 mph and going around our sun at 67,000 mph. Science is our instrument into the past and present life on this planet; evolution is that theory that ties it all together and we must accept it even though it seems counter intuitive. Whales really did evolve from a terrestrial animal the size of a raccoon. We really do share a common ancestor with chimps that lived about 6 million years ago. Evolution is true for all species, past and present. All life is connected through shared ancestry. Shared ERVs For brevity I have chosen only two examples that demonstrate evolution, macroevolution, is true. The DNA evidence of shared ERVs among the great apes which includes humans, is very sound and has withstood many years of attempts to discount it. Other DNA evidence discussed specifically include chromosomal fusions see here, and shared DNA repairs but not LTR divergent ratios, shared chromosomal inversions, shared synonymous mutations, shared pseudogenes and their mutations and comparative indel mutations (insertion/deletion). Of interest, at least 50% of human genomes are derived from viruses and repetitive sequences (Shubin even says 75%). What a strange way to construct humans, by using parasitic viruses that leave a trail of their attacks on ape genomes demonstrating evolution? From Reece et al. 2013. Campbell’s Biology. No copyright infringement intended. Fair use permitted. [Exons are the coding parts of DNA. Although Introns are non-coding they often have several functions. Transposons and repetitive DNA are often functionless and much is junk left over from evolution.] A look at where some of the retroelements come from. Note especially the retrotransposons and LINEs and how they relate to viral derivatives. From: http://flax.nzdl.org/greenstone3/flax;jsessionid=72A45BE2DD4B64EDEBE293D0976BC668?a=d&c=virology1&d=HASH01b21adcf515d44c441c5798&dt=simple&p.a=b&p.s=ClassifierBrowse Virology - Retroviral Derivations Vincent Racaniello, Lecture #9, 2013. Columbia University. Course: Virology No copyright infringement intended. Fair Use Permitted Whale Evolution. The evidence for whale evolution seems to me to be very convincing to an objective person. More than 220 fossil whale species have been found and described. The legs shrinking and vestigial pelvis is there for all to see. All those olfactory pseudogenes. A blowhole that starts at the nose and migrates to the top in embryos, and a migrating blow hole is demonstrated in the fossil record among so many other facts that point overwhelmingly to evolution. Sir Harold Kroto, PhD. Nobel Prize Winner : https://en.wikipedia.org/wiki/Harry_Kroto Treat Science Right and It Could Help Save the World https://www.sciencenews.org/article/treat-science-right-and-it-could-help-save-world If Not Evolution, Then What? In addition to whale evolution, other items to examine might include the Hawaiian Islands and the Emperor Seamounts. Those islands are about 2,500 miles away from any major land. One needs to explain without evolution how all those unique species got there, when, and why they resemble continental forms. Why some species are not found in the islands and only those that could float or get blown there became founder species, and then new species radiated out onto other islands from an ancestral species. Darwin’s Finches is an example on the Galapagos. How the hot spot of magma that is producing the Hawaiian islands as the plate moves over it did that without millions of years and also produced the worn down Emperor Seamounts that extend eastward thousands of miles without evolution seems like wishful thinking. And if one is going to move a plate that much in a year as some anti-evolutionists propose, the physics of heat production tell you that's impossible. See the Heat Problem immediately below for addressing groups that claim the earth is only a few thousands of years old. Begins at 7:00. Darwin of course derived much of his theory of Natural Selection from island biogeography. Even more basic to try and explain without evolution is the fossil record itself. About 15,000 feet of sedimentary rock in layers like a cake with fossils not mixing, going from simple to complex over 500 million years and with many transitional fossils where they should be if evolution were true. Wish to use a Global Flood as an explanation? Then why are the pterodactyls only found in one layer? If all the marine animals that ever lived were swimming at the same time, why are their fossils in sequence? Why do the plants also separate out by layers going from simple to complex? Why are fossil animals also found with fossil plants and pollen only found in certain layers? In a cataclysmic global Flood the best one could hope for are transitions of fossils between layers with some mixing. That’s exactly what we don’t find. As one person wrote, the DNA findings alone should result in a second Galileo Moment and the death of common design as an argument. I have presented shared ERVs as fantastic evidence for human evolution, but there are also many other DNA findings such as human chromosome 2 fusion and shared pseudogenes. Evolution explains that the human population never went below 10,000. Modern humans evolved over millions of years in populations in Africa and then moved out finally successfully to colonize the globe about 70,000 years ago after several outings did not “take”. Women have excruciating pain in childbirth, sometimes resulting in the death of one or both of them, because of the evolution of bipedalism. Any low back or sinus problems you have is also probably due to evolution since natural selection can only work with what it’s got. You must have vitamin C in your diet or you develop a disease called scurvy (and why British sailors were called “Limeys” because they took them on board limes to avoid it), yet your cat and dog have plenty in their blood naturally because of evolution. You carry a dead gene, a pseudogene, for making egg yolk because of your ancestors and it matches the same homologous location in chickens. Because - evolution. Even Michael Behe of the Discovery Institute and the champion of the Intelligent Design Irreducible Argument accepts macroevolution with mutations occurring when necessary. Of course the Pope speaking for billions accepts evolution but with ensoulment at some time. Where the Rubber Meets the Road After the Site Conclusion, I will take a candid examination of a few of the many consequences and ramifications to our world views if evolution is true. If our origin is millions of years in the making what does that mean for us living today? What does it mean if we are connected to all life? If we are here because of evolution that adapted humans to situations that often now are nonexistent, how do we respond to urges like tribalism or its larger cousin nationalism that now threatens our societies? Are people morally responsible for bad behavior? What does it mean to have morals in a world view on evolution? We Can Still See these 5 Traces of Ancestor Species in All Human Bodies Today https://theconversation.com/we-can-still-see-these-5-traces-of-ancestor-species-in-all-human-bodies-today-197011#Echobox=1674422517