NEANDERTHALS, DNA AND HUMANS

A study in Science on DNA from both Neanderthal and Homo sapiens indicated that the genomes for both groups are greater than 99.5 percent identical. Other studies have shown non-Africans today carry 1 to 6 percent of Neanderthal DNA. As of July 2017, number of Neanderthals from whom we have genetic information was 18.

According to DNA taken from a 50,000-year-old a fossilized Neanderthal toe bone found in a Siberian Cave: 2 percent of the DNA of modern people not of African descent came from Neanderthals and 0.5 percent of Denisovan DNA came from Neanderthals, and that an estimated 0.2 percent of the DNA of mainland Asians and Native Americans comes from Denisovans. [Source: Monte Morin, Los Angeles Times, December 18, 2013 \=]

Chris Stringer wrote in The Guardian: “Recent massive improvements in recovery and analysis of ancient DNA have produced even more information, some of it very surprising. Fossil fragments from Croatia have yielded up a nearly entire Neanderthal genome, providing rich data that promise insights into their biology – from eye colour and hair type through to skull shape and brain functions. These latest results have largely confirmed a separation from our lineage” hundreds of thousands of “years ago. But when the new Neanderthal genome was compared in detail with modern humans from different continents, the results produced an intriguing twist to our evolutionary story: the genomes of people from Europe, China and New Guinea lay slightly closer to the Neanderthal sequence than did those of Africans. Thus if you are European, Asian or New Guinean, you could have 2.5 percent of Neanderthal DNA in your genetic make-up. [Source: Chris Stringer, The Guardian, June 19, 2011. Stringer is head of human origins at the Natural History Museum in London |=|]

“The most likely explanation for this discovery is that the ancestors of today's Europeans, Asians and New Guineans interbred with Neanderthals (or at least with a population that had a component of Neanderthal genes) in North Africa, Arabia or the Middle East, as they exited Africa about 60,000 years ago. That ancient human exodus may have involved only a few thousand people, so it would have taken the absorption of only a few Neanderthals into a group of H. sapiens for the genetic effect – greatly magnified as modern human numbers exploded – to be felt tens of thousands of years later.” |=|

Websites and Resources on Neanderthals: Wikipedia: Neanderthals Wikipedia ; Neanderthals Study Guide thoughtco.com ; Neandertals on Trial, from PBS pbs.org/wgbh/nova; The Neanderthal Museum neanderthal.de/en/ ; The Neanderthal Flute, by Bob Fink greenwych.ca. Websites and Resources on Prehistoric Art: Chauvet Cave Paintings archeologie.culture.fr/chauvet ; Cave of Lascaux archeologie.culture.fr/lascaux/en; Trust for African Rock Art (TARA) africanrockart.org; Bradshaw Foundation bradshawfoundation.com; Australian and Asian Palaeoanthropology, by Peter Brown peterbrown-palaeoanthropology.net.

Websites and Resources on Hominins and Human Origins: Smithsonian Human Origins Program humanorigins.si.edu ; Institute of Human Origins iho.asu.edu ; Becoming Human University of Arizona site becominghuman.org ; Talk Origins Index talkorigins.org/origins ; Last updated 2006. Hall of Human Origins American Museum of Natural History amnh.org/exhibitions ; Wikipedia article on Human Evolution Wikipedia ; Human Evolution Images evolution-textbook.org; Hominin Species talkorigins.org ; Paleoanthropology Links talkorigins.org ; Britannica Human Evolution britannica.com ; Human Evolution handprint.com ; National Geographic Map of Human Migrations genographic.nationalgeographic.com ; Humin Origins Washington State University wsu.edu/gened/learn-modules ; University of California Museum of Anthropology ucmp.berkeley.edu; BBC The evolution of man" bbc.co.uk/sn/prehistoric_life; "Bones, Stones and Genes: The Origin of Modern Humans" (Video lecture series). Howard Hughes Medical Institute.; Human Evolution Timeline ArchaeologyInfo.com ; Walking with Cavemen (BBC) bbc.co.uk/sn/prehistoric_life ; PBS Evolution: Humans pbs.org/wgbh/evolution/humans; PBS: Human Evolution Library www.pbs.org/wgbh/evolution/library; Human Evolution: you try it, from PBS pbs.org/wgbh/aso/tryit/evolution; John Hawks' Anthropology Weblog johnhawks.net/ ; New Scientist: Human Evolution newscientist.com/article-topic/human-evolution; Fossil Sites and Organizations: The Paleoanthropology Society paleoanthro.org; Institute of Human Origins (Don Johanson's organization) iho.asu.edu/; The Leakey Foundation leakeyfoundation.org; The Stone Age Institute stoneageinstitute.org; The Bradshaw Foundation bradshawfoundation.com ; Turkana Basin Institute turkanabasin.org; Koobi Fora Research Project kfrp.com; Maropeng Cradle of Humankind, South Africa maropeng.co.za ; Blombus Cave Project web.archive.org/web; Journals: Journal of Human Evolution journals.elsevier.com/; American Journal of Physical Anthropology onlinelibrary.wiley.com; Evolutionary Anthropology onlinelibrary.wiley.com; Comptes Rendus Palevol journals.elsevier.com/ ; PaleoAnthropology paleoanthro.org.

DNA Studies, Neanderthals and Modern Men

Neanderthal DNA extraction

A study based on genetic material taken the skull of the original Neanderthal specimen found in the Neander Valley in Germany, indicate that Neanderthals were quite clearly a separate species from “Homo sapiens “ and that they probably added nothing to the gene pool of modern humans.

According to a 1997 study by Svante Paabo, then of the University Munich, published the journal Cell, the genetic material of Neanderthals differ about half as much from modern humans as modern humans do from chimpanzees. The study based on studies of Neanderthal mitochondrial DNA, suggests that Neanderthals and “Homo sapiens” had a common ancestor and diverged as separate paths from the “ Homo” family tree about 700,000 to 600,000 years ago. The common ancestor is believed by some to be “Homo heidelbergensis” although other believe that it was an ancestor to Neanderthals alone.

Modern humans differ from each other by an average of eight variations. The DNA taken from the right, upper arm bone of the Neanderthal specimen had 27 difference from modern humans, compared to 55 differences between modern humans and chimpanzees. The Neanderthal DNA differed just as much from modern humans from Africa and Asia as it did from modern humans from Europe. If Neanderthals were in fact ancestors of modern humans it would figure that they would share more genetic material with Europeans than groups from other parts of the world, but this is not case. The discovery of the 160,000-year-old modern human fossils in Ethiopia is further evidence that modern humans and Neanderthals evolved from separate lines.

Neanderthal DNA

In 2005, a team lead by Svante Paabo of the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany announced it was launching a project to reconstruct the Neanderthal genome. In 2006, it announced it had decoded fragments of Neanderthal DNA.

As of May 2010, the Neanderthal genome that had been reveled covered about 60 percent of the species full genetic code, with an international team of researchers revealing more ha 3 billion bits of DNA code. . The DNA had been extracted from six skeletons from four sites; the Vindija cave in Croatia, El Sidron in Spain, Mezmaiskaya in Russia and Feldhofer in the Neander Valley of Germany, with three small fragments of bone from Vindija providing most of the sequence.

20120201-svante paabo.jpg
Svante Paabo Paabo’s team initially examined about 60 Neanderthals of the 400 or so known Neanderthal specimens and found only two with viable genetic material. On top of that less than 5 percent of the material extracted from the bones turned out to be Neanderthal DNA. It took a lot laborious, time-consuming work to map out what they did.

Paabo’s team was able to construct the genome with DNA that has been degraded over time and applied the same technique to reconstructing the genome of mammoths and cave bears. Much of the DNA recovered from Neanderthals bones comes from microorganisms that colonized the tissues after death but enough Neanderthal DNA has been recovered, Paabo said to make it “technically feasible to achieve a reliable Neanderthal genome.” In addition to the colonizing microorganisms, scientists also had to make sure the Neanderthal DNA was not contaminated by human DNA from the scientists working with the samples.

Zach Zorich wrote in Archaeology magazine, “Although this sequence includes only 60 percent of the Neanderthal genome, it does provide some interesting insights into the biology of this distinctive human species. The sequence showed that variations in just one gene might account for the differences in the shape of the skull, rib cage, and shoulder joint between Neanderthals and modern humans. [Source: Zach Zorich, Archaeology magazine, January/February 2011]

A major insight came when researchers compared the Neanderthal DNA to the DNA of three modern people (one French, one Han Chinese, and one Polynesian). The team found that all three had inherited between 1 and 4 percent of their DNA from Neanderthals. They also compared the Neanderthal sequence to two African individuals (one Yoruba and one San) and found no indication that they had inherited genes from Neanderthals, who are known to have evolved outside Africa. The research supports the idea that Neanderthals interbred with Homo sapiens between 100,000 and 80,000 years ago as our anatomically modern ancestors left Africa and spread across the globe. [Ibid]

Sequencing Neanderthal DNA

Elizabeth Kolbert wrote in The New Yorker: The famed evolutionary geneticist Svante Pääbo was in Munich “when he got a call from the Rhenish State Museum, in Bonn. The museum houses the bones of the first Neanderthal to be identified as such, which was discovered in the summer of 1856. What did Pääbo think the odds were that he could extract usable DNA? He had no way of determining what kind of shape the bones were in until he dissolved them. “I didn’t know what to tell them, so I said, ‘There’s a five-per-cent chance that it works,’ ” he recalled. A few months later, he received a small chunk of the Neanderthal’s right humerus.[Source: Elizabeth Kolbert, The New Yorker, August 15, 2011 ]

“Pääbo announced his plan to sequence the entire Neanderthal genome in July, 2006, just in time for the hundred-and-fiftieth anniversary of the Neanderthal’s discovery. The announcement was made together with an American company, 454 Life Sciences, which had developed a so-called “high throughput” sequencing machine that, with the help of tiny resin spheres, could replicate tens of thousands of DNA snippets at a time. Both inside and outside the genetics profession, the plan was viewed as wildly ambitious, and the project made international news. “A STUDY WITH A LOT OF BALLS,” the headline in The Economist declared.

“By this point, a complete version of the human genome had been published. So, too, had versions of the chimpanzee, mouse, and rat genomes. But humans, chimps, mice, and rats are all living organisms, while Neanderthals have been extinct for thirty thousand years. The first hurdle was simply finding enough Neanderthal DNA to sequence. The chunk of the original Neanderthal that Pääbo had received had yielded shreds of genetic information, but nowhere near the quantities needed to assemble—or reassemble—an entire genome. So Pääbo was placing his hopes on another set of bones, from Croatia. (The Croatian bones turned out to have belonged to three individuals, all of them women; the original Neanderthal was probably a man.) “I wish I had that kind of energy.”

“Toward the end of 2006, Pääbo and his team reported that, using a piece of Croatian bone, they had succeeded in sequencing a million base pairs of the Neanderthal genome. (Just like the human genome, the full Neanderthal genome consists of roughly three billion base pairs.) Extrapolating from this, they estimated that to complete the project would take roughly two years and six thousand “runs” on a 454 Life Sciences machine. But later analysis revealed that the million base pairs had probably been contaminated by human DNA, a finding that led some geneticists to question whether Pääbo had rushed to publish results that he should have known were wrong. Meanwhile, subsequent bones yielded a much lower proportion of Neanderthal DNA and a much higher percentage of microbial DNA. (Something like eighty per cent of the DNA that has been sequenced for the Neanderthal Genome Project belongs to microorganisms and, as far as the project is concerned, is useless.) This meant the initial estimates of the labor involved in finishing the genome were probably far too low. “There were times when one despaired,” Pääbo told me. No sooner would one problem be resolved than another materialized. “It was an emotional roller coaster,” Ed Green, the biomolecular engineer from Santa Cruz, recalled.”

Human Neanderthal mtDNA

Neanderthal DNA and Out of Africa

Elizabeth Kolbert wrote in The New Yorker: “About two years into the project, a new puzzle arose. Pääbo had assembled an international team to help analyze the data the sequencing machines were generating—essentially, long lists of A’s, T’s, G’s, and C’s. Sifting through the data, one of the members of this team, David Reich, a geneticist at Harvard Medical School, noticed something odd. The Neanderthal sequences, as expected, were very similar to human sequences. But they were more similar to some humans than to others. Specifically, Europeans and Asians shared more DNA with Neanderthals than did Africans. “We tried to make this result go away,” Reich told me. “We thought, This must be wrong.” [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]

“For the past twenty-five years or so, the study of human evolution has been dominated by the theory known in the popular press as “Out of Africa” and in academic circles as the “recent single-origin” or “replacement” hypothesis. This theory holds that all modern humans are descended from a small population that lived in Africa roughly two hundred thousand years ago. (Not long before he died, Pääbo’s adviser Allan Wilson developed one of the key lines of evidence for the theory, based on a comparison of mitochondrial DNA from contemporary humans.)

“Around a hundred and twenty thousand years ago, a subset of the population migrated into the Middle East, and by fifty thousand years ago a further subset pushed into Eurasia. As they moved north and east, modern humans encountered Neanderthals and other so-called “archaic humans,” who already inhabited those regions. The modern humans “replaced” the archaic humans, which is a nice way of saying they drove them into extinction. This model of migration and “replacement” implies that the relationship between Neanderthals and humans should be the same for all people alive today, regardless of where they come from.”

“Leaky Replacement” Hypothesis

Elizabeth Kolbert wrote in The New Yorker: “Many members of Pääbo’s team suspected another case of contamination. At various points, the samples had been handled by Europeans; perhaps they had got their DNA mixed in with the Neanderthals’. Several tests were run to assess this possibility. The results were all negative. “We kept seeing this pattern, and the more data we got, the more statistically overwhelming it became,” Reich told me. [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]

Gradually, the other team members started to come around. In a paper published in Science, in May, 2010, they introduced what Pääbo has come to refer to as the “leaky replacement” hypothesis. (The paper was later voted the journal’s outstanding article of the year, and the team received a twenty-five-thousand-dollar prize.) Before modern humans “replaced” the Neanderthals, they had sex with them. The liaisons produced children, who helped to people Europe, Asia, and the New World.

“The leaky-replacement hypothesis—assuming for the moment that it is correct—provides further evidence of the closeness of Neanderthals to modern humans. Not only did the two interbreed; the resulting hybrid offspring were functional enough to be integrated into human society. Some of these hybrids survived to have kids of their own, who, in turn, had kids, and so on to the present day. Even now, at least thirty thousand years after the fact, the signal is discernible: all non-Africans, from the New Guineans to the French to the Han Chinese, carry somewhere between one and four per cent Neanderthal DNA.” When Pääbo “finally came around to the idea that Neanderthals bequeathed some of their genes to modern humans, he told me, “I thought it was very cool. It means that they are not totally extinct—that they live on a little bit in us.”“

20120205-CurratExcoffierNeandethal 2mtDNA.png

Neanderthal mtDNA maps

Common Ancestors and DNA Characteristics

Elizabeth Kolbert wrote in The New Yorker: “According to the most recent estimates, Neanderthals and modern humans share a common ancestor...(It is unclear who that ancestor was, though one possibility is the somewhat shadowy hominin known, after a jawbone found near Heidelberg, as Homo heidelbergensis.) The common ancestor of chimps and humans, by contrast, lived some five million to seven million years ago. This means that Neanderthals and humans had less than one-tenth the time to accumulate genetic differences. [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]

“Mapping these differences is, in principle, pretty straightforward—no harder, say, than comparing rival editions of “Hamlet.” In practice, it’s quite a bit more complicated. To begin with, there’s really no such thing as the human genome; everyone has his or her own genome, and they vary substantially—between you and the person sitting next to you on the subway, the differences are likely to amount to some three million base pairs. Some of these variations correspond to observable physiological differences—the color of your eyes, say, or your likelihood of developing heart disease—and some have no known significance. To a first approximation, a human and a Neanderthal chosen at random would also vary by three million base pairs. The trick is ascertaining which of these millions of variations divide us from them. Pääbo estimates that when the Neanderthal Genome Project is completed, the list of base-pair changes that are at once unique to humans and shared by all humans will number around a hundred thousand. Somewhere in this long list will lie the change—or changes—that made us human to begin with. Identifying these key mutations is where the transgenic mice come in.

“From an experimental viewpoint, the best way to test whether any particular change is significant would be to produce a human with the Neanderthal version of the sequence. This would involve manipulating a human stem cell, implanting the genetically modified embryo into a surrogate mother, and then watching the resulting child grow up. For obvious reasons, such Island of Dr. Moreau-like research on humans is not permitted, nor is it necessarily even possible. For similar reasons, such experimentation isn’t allowed on chimpanzees. But it is allowed on mice. Dozens of strains of mice have been altered to carry humanized DNA sequences, and new ones are being created all the time, more or less to order.”

FOXP2 and RUNX2 — Genes Involved in Language and Bone Formation

Elizabeth Kolbert wrote in The New Yorker: “Several years ago, Pääbo and a colleague, Wolfgang Enard, became interested in a gene known as FOXP2, which in humans is associated with language. (People who have a faulty copy of the gene—an extremely rare occurrence—are capable of speech, but what they say is, to strangers, mostly incomprehensible.) Pääbo and Enard had some mice bred with a humanized version of the gene, and then studied them from just about every possible angle. The altered mice, it turned out, squeaked at a lower pitch than their un-humanized peers. They also exhibited measurable differences in neural development. (While I was in Leipzig, I watched a graduate student cut the heads off some of the altered mice and then slice up their brains, like radishes.) [Source: Elizabeth Kolbert, The New Yorker, August 15, 2011]

“The Neanderthals’ FOXP2 gene, it turns out, is in almost all ways identical to humans’, but there is one suggestive base-pair difference. When this difference was discovered, it prompted Pääbo to order up a new round of transgenic mice, which, at the time of my visit, had just been born and were being raised under sterile conditions in the basement.

“Genes that seem to play a role in speech are obvious places to look for human-specific changes. But one of the main points of sequencing the Neanderthal genome is that the most obvious places to look may not be the right ones. “The great advantage with genomics in this form is that it’s unbiased,” Pääbo told me. “If you go after candidate genes, you’re inherently saying what you think the most important thing is. Language, many people would say. But perhaps we will be surprised—perhaps it’s something else that was really crucial.”

“Recently, Pääbo has become interested in a gene known as RUNX2, which is involved in bone formation. When members of his team analyzed the human and Neanderthal genomes mathematically, RUNX2 emerged as a place where significant changes in the human lineage seem to have occurred. People who have faulty copies of the RUNX2 gene often develop a condition, known as cleidocranial dysplasia, whose symptoms include such Neanderthal-like features as a flared rib cage. Two genes that have been implicated in autism, CADPS2 and AUTS2, also appear to have changed substantially between Neanderthals and humans. This is interesting because one of the symptoms of autism is an inability to read social cues.”

Neanderthal DNA comparison

DNA from Neanderthal Toe Reveals Interbreeding with Humans and Denisovans

A 50,000-year-old toe bone from a Neanderthal, discovered in Denisova Cave in Siberia, gave up DNA indicating interbreeding between Neanderthals, modern humans and Denisovans scientists reported in the journal Nature. DNA from the Neanderthal toe fossil was compared to the genomes of 25 present-day human and a group of Denisovans. According to their analysis, Neanderthals contributed roughly 2 percent of their DNA to modern people outside Africa and half a percent to Denisovans, who contributed 0.2 percent of their DNA to Asian and Native American people.[Source: Monte Morin, Los Angeles Times, December 18, 2013 \=]

Monte Morin wrote in the Los Angeles Time: “The biggest surprise, though, was the finding that a fourth hominin contributed roughly 6 percent of the DNA in the Denisovan genome. The identity of this DNA donor remains a mystery. “It is possible that this unknown hominin was what is known from the fossil record as Homo erectus,” said lead study author Kay Prufer, a geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Further studies are necessary to support or reject this possibility.” \=\

“Geneticists and anthropologists said the inch-long bone and resulting analysis have greatly illuminated a period of time roughly 12,000 to 126,000 years ago. It does seem that Eurasia during the Late Pleistocene was an interesting place to be a hominin, with individuals of at least four quite diverged groups living, meeting and occasionally having sex,” biologist Ewan Birney of the European Bioinformatics Institute and Stanford geneticist Jonathan Pritchard wrote in a commentary that accompanied the study. \=\

“The toe bone was discovered in an ancient natural shelter called Denisova Cave, in Siberia’s Altai Mountains. It was in the same cave that archaeologists discovered evidence of the Denisovans, who were recognized as a distinct group in 2010. Based on DNA taken from the toe bone, researchers were able to determine that it belonged to a female Neanderthal. They could also tell that her parents were very closely related, and “were either half siblings who had a mother in common, double first cousins, an uncle and a niece, an aunt and a nephew, a grandfather and a granddaughter, or a grandmother and a grandson,” they wrote in the study.

“Such inbreeding might have been necessary because the Neanderthal population was very small, perhaps already well on the road toward extinction, the study authors suggested. “The data are consistent with the population being small enough that breeding among relatives was reasonably common,” said UC Berkeley biologist Montgomery Slatkin, a member of the research team. DNA analysis of additional Neanderthal remains would be needed to confirm that hunch, Slatkin said.

“The study authors estimated that the ancestors of Neanderthals and Denisovans split from the lineage that led to modern humans roughly 600,000 years ago, and then split between each other roughly 400,000 years ago. Based on the genomes of each group, researchers concluded that all of their populations were in decline at least 1 million years ago. Sometime after that, our ancestors began to grow in number while the Neanderthal and Denisovan populations continued to shrink. Researchers estimate that Homo sapiens became the planet’s sole surviving humans roughly 30,000 years ago.

While the study’s conclusions were sure to fire the imagination of the general public, at least one outside expert said the anthropological sleuthing had just begun. John Hawks, a paleoanthropologist at the University of Wisconsin, Madison, said it was very difficult to pin down the timing and number of groups involved in genetic mixing. We could really be looking at mixture from multiple different populations with different histories,” Hawks said.

Study authors hope that by mapping the Neanderthal genome they might gain insights into the evolution of modern humans. The list of DNA sequences that distinguish us from Neanderthals is relatively short, according to the study’s senior author, Svante Paabo, director of the Max Planck Institute’s department of genetics. It’s a catalog of the genetic features that sets all modern humans apart from all other organisms living or extinct,” Paabo wrote in a statement released by the institute. “I believe that in it hide some of the things that made the enormous expansion of human populations and human culture and technology in the last 100,000 years possible.”

Fifth of Neanderthals' DNA Lives on in Modern Humans

About a fifth of the DNA carried today by the human population was also carried by Neanderthals, a result of sexual encounters scientists estimate took place Neanderthals and modern humans as they migrated out of Africa and into Eurasia about 65,000 years ago. Ian Sample wrote in The Guardian: “The populations of both groups were likely so small that interbreeding was a rare event, but the benefits of some Neanderthal genes were so great that they spread through the population and linger on in modern non-Africans today. The finding means that scientists can study about 20 percent of the Neanderthal genome without having to draw the genetic material from fragile and ancient fossils. [Source: Ian Sample, The Guardian, January 29, 2014]

“Benjamin Vernot and Joshua Akey at the University of Washington in Seattle sequenced the genomes of more than 600 people from Europe and eastern Asia. They then used a computer analysis to find gene variants that bore all the hallmarks of having come from Neanderthals. To see whether the technique worked, they checked the genes against the official Neanderthal genome, which was sequenced from fossil remnants in 2010 by researchers in Germany. |=|

“The researchers found that while most non-Africans carried 1 to 3 percent Neanderthal DNA, the total amount in modern humans reached about 20 percent. "Although Neanderthals are extinct, there's still a lot of genetic information about them floating around, in our own genomes. It's not necessarily useful in that it will cure cancer, but it helps us to learn about our history," Vernot told the Guardian. Details of the study are reported in Science. The researchers now believe that even deeper mining of modern genomes could help to find genetic traces of other archaic humans. |=|

“In a separate study published in Nature, David Reich at Harvard University looked for Neanderthal genes in the DNA of more than 1,000 living people. He found that the Neanderthals left a mark in distinct regions of the modern human genome, but in others left no trace at all. Many of the Neanderthal genes that live on in people today are involved in making keratin, a protein used in skin, hair and nails. Reich speculates that modern humans may have picked up Neanderthal genes that were better suited to the cold environment, perhaps because they produced more or thicker hair, or tougher skin. |=|

“More striking was that humans are missing Neanderthal DNA from many other regions of their genomes, which suggests that evolution steadily stripped the archaic DNA out until it vanished all together. Reich found that hardly any Neanderthal genes were expressed in modern men's testes, and that the X chromosome was almost completely devoid of Neanderthal DNA. That would happen if males with Neanderthal and modern human parents were infertile, because the males would never get to pass on their single Neanderthal X chromosome. "When Neanderthals and modern humans interbred they were actually at the edge of biological compatibility. They did interbreed, and Neanderthals left an important biological trace in modern humans, but nevertheless, the population had to sort out some problems afterwards, because certain Neanderthal variants led to reduced male fertility," said Reich. The finding suggests that most Neanderthal DNA found in humans today was passed down from females. |=|

"Anything related to maleness in the Neanderthal has been purged from our genomes," said Chris Stringer, head of human origins at the Natural History Museum in London. "Neanderthal DNA has come down to us today, but that transmission was mainly through the female line, because the males would have been significantly less fertile, and possibly even sterile." |=|

DNA IBD segment detected by HapFABIA in 1000 Genomes

Neanderthal DNA in Humans: Result of Common Ancestor Rather Than Sex

A study published in 2012 by researchers from the University of Cambridge in the journal Proceedings of the National Academy of Sciences. challenges the view humans and Neanderthals had inter-species sex, known as hybridisation, and said a better explantion for the presence of Neanderthal DNA in modern humans was the sharing a common ancestor. Mehreen Khan of Bloomberg wrote: “The Cambridge researchers examined demographic patterns suggesting humans were far from intimate with the species they displaced in Europe almost 40,000 years ago. ''The levels of hybridisation people have spoken about is too high,'' said Andrea Manica, a researcher from Cambridge University who wrote the study. ''If any hybridisation happened, then it would have been minimal.'' [Source: Mehreen Khan, Bloomberg, August 23, 2012 ||^||]

“A previous study in 2010 suggested that inter-species liaisons near the Middle East resulted in Neanderthal genes first entering humans 70,000 years ago. Modern non-Africans share more with Neanderthals than Africans, supporting the claim that the mixing occurred when the first early humans left Africa to populate Europe and Asia. ||^||

“The existence of a 500,000-year-old shared ancestor that predates the origin of Neanderthals provides a better explanation for the genetic mix, the Cambridge scientists said. Diversity within this ancestral species meant that northern Africans were more genetically similar to their European counterparts than southern Africans through geographic proximity, Manica said. This likeness persisted over time to account for the overlap with the Neanderthal genome we see in modern people today. ''Differences between populations can be explained by common ancestry,'' said Manica, whose research was funded by the Biotechnology and Biological Sciences Research Council and the Leverhulme Trust. ''Northern Africans would be more similar to Europeans and ancient similarity stayed because there wasn't enough mixing between northern and southern Africans.'' ||^||

“Population diversity, known as substructure, can't explain data on the shared genes, said David Reich, a professor of genetics at Harvard Medical School in Boston and author of the 2010 study. ''We have ruled out the possibility that ancient substructure can explain all the evidence of greater relatedness of Neanderthals to non-Africans than to Africans,'' Reich said. Hybridisation between Neanderthals and humans can never be disproved entirely, according to Manica, who questioned what inter-species breeding may mean for the human genome today. ''The further we bring down the level of hybridisation, the more unlikely it is it would have shaped the ways modern humans evolved,'' Manica said. ||^||

Why Neanderthals, Humans Likely Produced Few Kids

Humans carry around a significant amount of Neanderthal DNA by why don’t they carry more? Charles Q. Choi of Live Science wrote: “Turns out, the Y chromosome may have been key in keeping the two lineages apart by creating conditions that might often have led to miscarriages if or when the two got together, researchers now say. [Source: Charles Q. Choi, LiveScience.com, April 11, 2016 +++]

“The last major component of the Neanderthal genome that scientists had not analyzed was the Y chromosome. In modern humans and Neanderthals, the Y chromosome determines if someone is male in sex. Now researchers have completed the first in-depth analysis of a Neanderthal Y chromosome. They focused on a Neanderthal male found in El Sidrón, Spain. Overall, the differences between the Neanderthal and modern human Y chromosomes suggest these lineages diverged almost 590,000 years ago, consistent with previous research. +++

“The Neanderthal Y chromosome was genetically distinct from any seen in modern humans. This suggests that this El Sidrón male's lineage is extinct, without any living carriers in modern humans. It remains uncertain how much other Neanderthal Y chromosomes resembled or differed from this one. Further analysis revealed that genetic mutations might explain why this Neanderthal Y chromosome was lost in modern humans. Three mutations seen on this chromosome generate molecules that can trigger immune responses from women during pregnancy that can lead to miscarriages, and two of these three mutations are unique to Neanderthals. +++

“The researchers suggest that such genetic incompatibilities between Neanderthals and modern humans may have helped drive these lineages apart by discouraging interbreeding between them. "We should pay attention to the potential role of immune incompatibilities in population isolation," study lead author Fernando Mendez, a population geneticist at Stanford University, told Live Science. +++

“In future research, scientists could analyze more Y chromosomes from a variety of male Neanderthals, Mendez said. Lab experiments could then determine the effect of these newfound Neanderthal mutations on interactions between male cells and female immune cells. The result might also confirm the idea that these mutations helped keep Neanderthals and modern humans apart, he added. Mendez and his colleaguesdetailed their findings in the April 7, 2016 issue of the American Journal of Human Genetics.” +++

Modern Human Health Issues May Influenced by Neanderthal DNA

DNA passed on from Neanderthals to modern humans appears to influenced the health of modern humans living today. Ian Sample wrote in The Guardian: Prehistoric couplings between Neanderthal and modern humans left all non-Africans today carrying 1-6 percent of Neanderthal DNA. People whose ancestors never left the continent would not have crossed paths with Neanderthals or the Denisovans, a mysterious group of humans who lived in and around Siberia at the same time. [Source: Ian Sample, The Guardian January 7, 2016]

Paul Jongko wrote in Listverse: “Depression, nicotine addiction, and heart attacks are some of the health problems that plague our society today. Though these diseases appear modern, new research from the Vanderbilt University and the University of Washington suggests that these illnesses could have originated from the Neanderthals. The co-author of the study, Joshua Akey, said, “You can blame your Neanderthal ancestry a little—but not too much—for whatever range of afflictions you have.” [Source: Paul Jongko, Listverse, May 14, 2016]

“Researchers Akey and John Capra made the discovery after examining the medical records and genes of 28,000 people. The records allowed the scientists to determine the health conditions of the subjects, and their genes enabled them to find the DNA that was inherited from the Neanderthals. It was clear that the presence of Neanderthal DNA had slightly increased the subject’s health risks”.

Neanderthal Passed on Thick Skin DNA to Humans

It seems likely that Neanderthal DNA that survives in modern humans helped them adapt to cold Europe by giving them thicker skin, researchers said. AFP reported: “Humans acquired Neanderthal DNA through interbreeding between 40 000 and 80 000 years ago which resulted in today's European and East Asian populations, scientists believe. Indigenous Africans have little or no Neanderthal DNA as their ancestors did not interbreed with Neanderthals, who lived in Europe and Asia. [Source: Mariette Le Roux, AFP, 30 January 2014 ^^]

“The latest research showed that the Neanderthal's DNA influence on humans was not evenly distributed across the human genome. Two separate studies, one in the British journal Nature and the other in US-based Science, reported finding concentrations of Neanderthal DNA in genes that influence skin and hair characteristics. The Nature team, which included scientists from Harvard, the Broad Institute in Cambridge and the Max Planck Institute for Evolutionary Anthropology in Germany, analysed and compared the genomes of 846 people of non-African heritage, 176 Africans, and a 50 000-year-old Neanderthal. The authors of the paper in Science, using statistical simulations with the genome sequences of 379 European and 286 East Asian individuals and one Neanderthal, came to a similar conclusion on our distant cousin's influence on human skin-related genes. ^^

“Among other things, these genes influence the production of keratin - a fibrous protein that lends toughness to skin, hair and nails and may have provided thicker insulation against a colder climate as homo sapiens moved northwards out of Africa, the authors of the Nature paper said. “Thus, Neanderthal alleles (gene variations) that affect skin and hair may have helped modern humans to adapt to non-African environments,” said the study. “It's tempting to think that Neanderthals were already adapted to the non-African environment and provided this genetic benefit to humans,” added co-author David Reich, a genetics professor at Harvard Medical School. ^^

“Recent research has concluded that humans trace about two percent of their genome to Neanderthals, but these claim to be the first studies to show the biological effect that the transfer has had on human development. Both studies found regions on the human genome that were devoid of Neanderthal DNA and concluded that certain genes must have been detrimental to humans and could not be tolerated. These Neanderthal-barren areas were mostly found on genes linked to functioning of the testes and the X chromosome, leading researchers to conclude the genetic exchange had threatened male fertility and had to be undone through a process of natural selection.” ^^

Neanderthals and Denisovans Strengthened Our Immune System?

Research from Stanford, the Max Planck Institute for Evolutionary Anthropology and the Institute Pasteur have suggested interbreeding with the Neanderthals strengthened the immune system of modern humans. Linda Marsa wrote in Discover: “When our ancestors mated with Neanderthals and Denisovans, a recently discovered archaic human group, they picked up some of their genes. Now researchers say that DNA inherited from these extinct hominins may have fortified the modern immune system. A team at Stanford University focused on human leukocyte antigen (HLA) class 1 genes, which play a vital role in rallying the immune system to fight off bacteria and viruses. Because diseases can be endemic to specific regions of the world, these genes exist in thousands of versions, known as alleles. [Source: Linda Marsa, Discover, December 22, 2011]

“To analyze the origin of these alleles, the scientists looked at bone marrow registries containing the HLA genes of millions of people from all parts of the globe. By comparing DNA from modern populations with the reconstructed genomes of Neanderthals and Denisovans, they discovered that several HLA variants from the archaic groups are still around. For example, the ancient gene for HLA-A, which helps the body resist viruses like Epstein-Barr, is present in half of all modern Europeans, more than 70 percent of Asians, and up to 95 percent of people in Papua New Guinea. Other ancient alleles are involved in the regulation of natural killer cells, essential for immune defense.

“Our ancestors’ liaisons with Neanderthals and Denisovans may have made them less susceptible to local infections, proposes Stanford immunologist Laurent Abi-Rached, giving them a survival advantage as they migrated out of Africa to Europe and Asia. “Breeding with our evolutionary cousins may have facilitated the spread of modern humans by preventing them from getting sick.”“

Neanderthals Gave Us Diabetes?

Paul Jongko wrote in Listverse: “Harvard geneticist David Altshuler and his colleagues suggested that modern humans might have gotten the diabetes mutations from Neanderthals. This discovery was made several years after the Max Planck Institute for Evolutionary Anthropology sequenced the DNA of a Neanderthal from a fossil. The researchers were quick to point out that their findings don’t necessarily prove that our extinct cousins suffered from diabetes. It just means that the mutations that cause type 2 diabetes, especially among Latinos and Asians, originated from them. [Source: Paul Jongko, Listverse, May 14, 2016]

“Altshuler and his colleagues made the discovery after examining the DNA of 8,000 residents of Mexico and Latin America. The people chosen for the research were of Native American and European descent. Though the link between modern-day diabetes and Neanderthals is fascinating, the researchers emphasized that the essence of their work is the development of new treatments that could potentially eradicate this global health problem.”

Researchers wrote in studies in Nature and Science that Neanderthals also conferred a risk for conditions like type-2 diabetes and Crohn's disease. The Nature team, which included scientists from Harvard, the Broad Institute in Cambridge and the Max Planck Institute for Evolutionary Anthropology in Germany, analysed and compared the genomes of 846 people of non-African heritage, 176 Africans, and a 50 000-year-old Neanderthal. The authors of the paper in Science, using statistical simulations with the genome sequences of 379 European and 286 East Asian individuals and one Neanderthal, came to a similar conclusion on our distant cousin's influence on human skin-related genes.[Source: Mariette Le Roux, AFP, 30 January 2014 ^^]

According to AFP: They “concluded that as much as 20 percent of the Neanderthal genome could be reconstituted today by adding up the totality of the DNA signature still lingering in modern humans. “If you look at enough individuals (we estimate about 2 000), you could theoretically identify all of the Neanderthal genome that still remains in modern humans,” Benjamin Vernot from the University of Washington's department of genome sciences, a co-author of the Science paper, told AFP. “Unfortunately, it's difficult to tell some Neanderthal DNA from human DNA, just because it's still pretty similar to ours. So while there might be 50 percent of the Neanderthal genome still floating around in modern humans, we were only able to identify 20 percent.” ^^

“The team had identified between 300 and 400 genes per individual that were at least partly Neanderthal, he said, but these were different from person to person. Both studies found regions on the human genome that were devoid of Neanderthal DNA and concluded that certain genes must have been detrimental to humans and could not be tolerated. These Neanderthal-barren areas were mostly found on genes linked to functioning of the testes and the X chromosome, leading researchers to conclude the genetic exchange had threatened male fertility and had to be undone through a process of natural selection.” ^^

Human-Neanderthal Gene Variance Involved in Autism

A structure that represents the biggest known genetic difference between humans and Neanderthals also predisposes humans to autism, a study by an international team of researchers led by University of Washington Medicine genome scientist Evan Eichler published in Nature in August 2016. Michael McCarthy wrote in the Medical Press: “The structure involves a segment of DNA on chromosome 16 that contains 28 genes. This segment is flanked by blocks of DNA whose sequences repeat over and over. Such stretches of duplicated DNA, called copy-number variants, are common in the human genome and often contain multiple copies of genes. Although most copy-number variants seem to have no adverse effect on health, some have been linked to disease. “However, when both strands of a segment of DNA are flanked by highly identical sequences, they can be susceptible to large copy-number differences, including deletion, duplication and other changes, during the process of cell division. In this case, deletion, which causes the loss of the segment's 28 genes, results in autism. [Source: Michael McCarthy, Medical Press, August 4, 2016]

“In the new study, researchers determined that this structure, located at a region on chromosome 16 designated 16p11.2, first appeared in our ancestral genome about 280,000 years ago, shortly before modern humans, Homo sapiens, emerged. This organization is not seen in any other primate – not chimps, gorillas, orangutans nor the genomes of our closest relatives, the Neanderthals and Denisovans. Yet today, despite the fact that the structure is a relatively new genetic change, it is found in genomes of humans the world over. "Most duplications in our genome are millions of years old, and the speed at which this structure transformed our genome is unprecedented," said co-author Eichler, a professor of genome sciences and an investigator of the Howard Hughes Medical Institute. "The wide and rapid distribution of these copy-number variants suggests the genes within the repetitive sections confer benefit that outweigh the disadvantages that come with the increased risk of autism in some offspring, should deletion occur."

“Copy-number variants may play an important role in human evolution because, as a species, we are relatively uniform genetically. "If you took two chimps out of the wild, they would have twice as many genetic differences in their genomes than you would see between two humans. And orangutans have three times as many differences. Having these structures means we have a way to radically restructure our genome over a very short time frame, bringing about changes that might otherwise take hundreds of millions of years of evolution to acquire – but at the cost of an increased risk of autism and other neuropsychiatric disorders," he said.

“One benefit of copy-number variants: They contain multiple copies of genes that can mutate and acquire new, potentially useful functions. Of particular interest to the researchers was a gene in the copy-number variants at 16p11.2 called BOLA2, multiple copies of which were found in both flanking regions. The BOLA2 protein in human cells appears to form a complex with another protein, called glutaredoxin 3, that allows the cells to capture iron more efficiently and make it available to proteins that require it. This effect appears to be most pronounced early in cell development. "This ability to help humans to acquire and use this essential element early in life might confer a significant enough benefit to outweigh the risk of having some offspring with autism," Eichler said.

“In addition to BOLA2, the mutations within the copy number variant regions appears to have created new protein formed by fusing two regions of the BOLA2 gene with three regions of another gene. This new gene may be the first completely new gene that distinguishes humans from our Neanderthal and ancient hominin cousins, Eichler said. Exactly what role the new protein it creates plays remains unknown. "We're going to work with other research teams to find out what it does but so far we haven't a clue."”

Image Sources: Wikimedia Commons

Text Sources: National Geographic, New York Times, Washington Post, Los Angeles Times, Smithsonian magazine, Nature, Scientific American. Live Science, Discover magazine, Discovery News, Ancient Foods ancientfoods.wordpress.com ; Times of London, Natural History magazine, Archaeology magazine, The New Yorker, Time, Newsweek, BBC, The Guardian, Reuters, AP, AFP, Lonely Planet Guides, “World Religions” edited by Geoffrey Parrinder (Facts on File Publications, New York); “History of Warfare” by John Keegan (Vintage Books); “History of Art” by H.W. Janson (Prentice Hall, Englewood Cliffs, N.J.), Compton’s Encyclopedia and various books and other publications.

Last updated September 2018