The morphological features typical of Neandertals first appear in the European fossil record about 400,000 years ago (1–3). Progressively more distinctive Neandertal forms subsequently evolved until Neandertals disappeared from the fossil record about 30,000 years ago (4). During the later part of their history, Neandertals lived in Europe and Western Asia as far east as Southern Siberia (5) and as far south as the Middle East. During that time, Neandertals presumably came into contact with anatomically modern humans in the Middle East from at least 80,000 years ago (6, 7) and subsequently in Europe and Asia.
Neandertals are the sister group of all present-day humans. Thus, comparisons of the human genome to the genomes of Neandertals and apes allow features that set fully anatomically modern humans apart from other hominin forms to be identified. In particular, a Neandertal genome sequence provides a catalog of changes that have become fixed or have risen to high frequency in modern humans during the last few hundred thousand years and should be informative for identifying genes affected by positive selection since humans diverged from Neandertals.
Substantial controversy surrounds the question of whether Neandertals interbred with anatomically modern humans. Morphological features of present-day humans and early anatomically modern human fossils have been interpreted as evidence both for (8, 9) and against (10, 11) genetic exchange between Neandertals and the presumed ancestors of present-day Europeans. Similarly, analysis of DNA sequence data from present-day humans has been interpreted as evidence both for (12, 13) and against (14) a genetic contribution by Neandertals to present-day humans. The only part of the genome that has been examined from multiple Neandertals, the mitochondrial DNA (mtDNA) genome, consistently falls outside the variation found in present-day humans and thus provides no evidence for interbreeding (15–19). However, this observation does not preclude some amount of interbreeding (14, 19) or the possibility that Neandertals contributed other parts of their genomes to present-day humans (16). In contrast, the nuclear genome is composed of tens of thousands of recombining, and hence independently evolving, DNA segments that provide an opportunity to obtain a clearer picture of the relationship between Neandertals and present-day humans.
A challenge in detecting signals of gene flow between Neandertals and modern human ancestors is that the two groups share common ancestors within the last 500,000 years, which is no deeper than the nuclear DNA sequence variation within present-day humans. Thus, even if no gene flow occurred, in many segments of the genome, Neandertals are expected to be more closely related to some present-day humans than they are to each other (20). However, if Neandertals are, on average across many independent regions of the genome, more closely related to present-day humans in certain parts of the world than in others, this would strongly suggest that Neandertals exchanged parts of their genome with the ancestors of these groups.
Several features of DNA extracted from Late Pleistocene remains make its study challenging. The DNA is invariably degraded to a small average size of less than 200 base pairs (bp) (21, 22), it is chemically modified (21, 23–26), and extracts almost always contain only small amounts of endogenous DNA but large amounts of DNA from microbial organisms that colonized the specimens after death. Over the past 20 years, methods for ancient DNA retrieval have been developed (21, 22), largely based on the polymerase chain reaction (PCR) (27). In the case of the nuclear genome of Neandertals, four short gene sequences have been determined by PCR: fragments of the MC1R gene involved in skin pigmentation (28), a segment of the FOXP2 gene involved in speech and language (29), parts of the ABO blood group locus (30), and a taste receptor gene (31). However, although PCR of ancient DNA can be multiplexed (32), it does not allow the retrieval of a large proportion of the genome of an organism.
The development of high-throughput DNA sequencing technologies (33, 34) allows large-scale, genome-wide sequencing of random pieces of DNA extracted from ancient specimens (35–37) and has recently made it feasible to sequence genomes from late Pleistocene species (38). However, because a large proportion of the DNA present in most fossils is of microbial origin, comparison to genome sequences of closely related organisms is necessary to identify the DNA molecules that derive from the organism under study (39). In the case of Neandertals, the finished human genome sequence and the chimpanzee genome offer the opportunity to identify Neandertal DNA sequences (39, 40).
A special challenge in analyzing DNA sequences from the Neandertal nuclear genome is that most DNA fragments in a Neandertal are expected to be identical to present-day humans (41). Thus, contamination of the experiments with DNA from present-day humans may be mistaken for endogenous DNA. We first applied high-throughput sequencing to Neandertal specimens from Vindija Cave in Croatia (40, 42), a site from which cave bear remains yielded some of the first nuclear DNA sequences from the late Pleistocene in 1999 (43). Close to one million bp of nuclear DNA sequences from one bone were directly determined by high-throughput sequencing on the 454 platform (40), whereas DNA fragments from another extract from the same bone were cloned in a plasmid vector and used to sequence ~65,000 bp (42). These experiments, while demonstrating the feasibility of generating a Neandertal genome sequence, were preliminary in that they involved the transfer of DNA extracts prepared in a clean-room environment to conventional laboratories for processing and sequencing, creating an opportunity for contamination by present-day human DNA. Further analysis of the larger of these data sets (40) showed that it was contaminated with modern human DNA (44) to an extent of 11 to 40% (41). We employed a number of technical improvements, including the attachment of tagged sequence adaptors in the clean-room environment (23), to minimize the risk of contamination and determine about 4 billion bp from the Neandertal genome.
Eliza Strickland at Discover:
Researchers from Germany’s Max Planck Institute for Evolutionary Anthropology first sequenced the entire Neanderthal genome from powdered bone fragments found in Europe and dating from 40,000 years ago–a marvelous accomplishment in itself. Then, they compared the Neanderthal genome to that of five modern humans, including Africans, Europeans, and Asians. The researchers found that between 1 percent and 4 percent of the DNA in modern Europeans and Asians was inherited from Neanderthals, which suggests that the interbreeding took place after the first groups of humans left Africa.
Anthropologists have long speculated that early humans may have mated with Neanderthals, but the latest study provides the strongest evidence so far, suggesting that such encounters took place around 60,000 years ago in the Fertile Crescent region of the Middle East [The Guardian].
The study, published in Science and made available to the public for free, opens up new areas for research. Geneticists will now probe the function of the Neanderthal genes that humans have hung on to, and can also look for human genes that may have given us a competitive edge over Neanderthals.
Erik Trinkaus, an anthropologist at Washington University in St. Louis, who has long argued that Neanderthals contributed to the human genome, welcomed the study, commenting that now researchers “can get on to other things than who was having sex with who in the Pleistocene”
Neanderthals lived in much of Europe and western Asia before dying out 30,000 years ago. They coexisted with humans in Europe for thousands of years, and fossil evidence led some scientists to speculate that interbreeding may have occurred there. But the Neanderthal DNA signal shows up not only in the genomes of Europeans, but also in people from East Asia and Papua New Guinea, where Neanderthals never lived.
“The scenario is not what most people had envisioned,” Green said. “We found the genetic signal of Neanderthals in all the non-African genomes, meaning that the admixture occurred early on, probably in the Middle East, and is shared with all descendants of the early humans who migrated out of Africa.”
The study did not address the functional significance of the finding that between 1 and 4 percent of the genomes of non-Africans is derived from Neanderthals. But Green said there is no evidence that anything genetically important came over from Neanderthals. “The signal is sparsely distributed across the genome, just a ‘bread crumbs’ clue of what happened in the past,” he said. “If there was something that conferred a fitness advantage, we probably would have found it already by comparing human genomes.”
The draft sequence of the Neanderthal genome is composed of more than 3 billion nucleotides–the “letters” of the genetic code (A, C, T, and G) that are strung together in DNA. The sequence was derived from DNA extracted from three Neanderthal bones found in the Vindiga Cave in Croatia; smaller amounts of sequence data were also obtained from three bones from other sites. Two of the Vindiga bones could be dated by carbon-dating of collagen and were found to be about 38,000 and 44,000 years old.
Deriving a genome sequence–representing the genetic code on all of an organism’s chromosomes–from such ancient DNA is a remarkable technological feat. The Neanderthal bones were not well preserved, and more than 95 percent of the DNA extracted from them came from bacteria and other organisms that had colonized the bone. The DNA itself was degraded into small fragments and had been chemically modified in many places.
Carl Zimmer at Discover:
Ideas about our own kinship to Neanderthals have swung dramatically over the years. For many decades after their initial discovery, paleoanthropologists only found Neanderthal bones in Europe. Many researchers decided, like Schaafhausen, that Neanderthals were the ancestors of living Europeans. But they were also part of a much larger lineage of humans that spanned the Old World. Their peculiar features, like the heavy brow, were just a local variation. Over the past million years, the linked populations of humans in Africa, Europe, and Asia all evolved together into modern humans.
In the 1980s, a different view emerged. All living humans could trace their ancestry to a small population in Africa perhaps 150,000 years ago. They spread out across all of Africa, and then moved into Europe and Asia about 50,000 years ago. If they encountered other hominins in their way, such as the Neanderthals, they did not interbreed. Eventually, only our own species, the African-originating Homo sapiens, was left.
The evidence scientists marshalled for this “Out of Africa” view of human evolution took the form of both fossils and genes. The stocky, heavy browed Neanderthals did not evolve smoothly into slender, flat-faced Europeans, scientists argued. Instead, modern-looking Europeans just popped up about 40,000 years ago. What’s more, they argued, those modern-looking Europeans resembled older humans from Africa.
At the time, geneticists were learning how to sequence genes and compare different versions of the same genes among individuals. Some of the first genes that scientists sequenced were in the mitochondria, little blobs in our cells that generate energy. Mitochondria also carry DNA, and they have the added attraction of being passed down only from mothers to their children. The mitochondrial DNA of Europeans was much closer to that of Asians than either was to Africans. What’s more, the diversity of mitochondrial DNA among Africans was huge compared to the rest of the world. These sorts of results suggested that living humans shared a common ancestor in Africa. And the amount of mutations in each branch of the human tree suggested that that common ancestor lived about 150,000 years ago, not a million years ago.
Over the past 30 years, scientists have battled over which of these views–multi-regionalism versus Out of Africa–is right. And along the way, they’ve also developed more complex variations that fall in between the two extremes. Some have suggested, for example, that modern humans emerged out of Africa in a series of waves. Some have suggested that modern humans and other hominins interbred, leaving us with a mix of genetic material.
Reconstructing this history is important for many reasons, not the least of which is that scientists can use it to plot out the rise of the human mind. If Neanderthals could make their own jewelry 50,000 years ago, for example, they might well have had brains capable of recognizing themselves as both individuals and as members of a group. Humans are the only living animals with that package of cognitive skills. Perhaps that package had already evolved in the common ancestor of humans and Neanderthals. Or perhaps it evolved independently in both lineages.
Razib Khan at Discover
If you had to sum up in a few words, what does this mean for paleoanthropology?
These scientists have given an immense gift to humanity.
I’ve been comparing it to the pictures of Earth that came back from Apollo 8. The Neandertal genome gives us a picture of ourselves, from the outside looking in. We can see, and now learn about, the essential genetic changes that make us human — the things that made our emergence as a global species possible.
And in doing so, they’ve taken a forgotten group of people — whom even most anthropologists had given up on — and they’ve restored them to their rightful place in our heritage.
Beyond that, they’ve taken all of their data and deposited it in a public database, so that the rest of us can inspect them, replicate results, and learn new things from them. High school kids can download this stuff and do science fair projects on Neandertal genomics.
This is what anthropology ought to be.
What did they sequence?
The Max Planck group obtained most of their genomic sequence from three specimens from Vindija — Vi33.16, Vi33.25, and Vi33.26. These are all postcranial fragments with minimal anatomical information. Green and colleagues were able to establish that the three bones represent different women, and that Vi33.16 and Vi33.26 may represent maternal relatives.
From these skeletons they got 5.3 billion bases of sequence. All this from an amount of bone powder about equal in mass to an aspirin pill.
Amazing. I mean, I know the folks at Max Planck are reading this. It’s inspiring to see what they’ve been able to do. These are three pieces of barely diagnostic hominin bone, and they’ve obtained literally hundreds of times more information than we have ever gotten from the fossil record of Neandertals.
I’ll describe the analyses of genetic similarity with humans in more detail below. As a brief summary, of those positions where the human genome differs from chimpanzees, Neandertals have the chimpanzee version around 12.7 percent of the time — meaning that across the genome, a Neandertal and a human will share a genetic ancestor an average of around 800,000 years ago. This is a couple hundred thousand years higher than the same number if we compare two humans to each other. The higher age of genetic common ancestors reflects partial isolation between the Neandertal population and the African populations that gave rise to most of our current genetic variation.
The team were able to identify 111 candidate duplications, almost all of which have some evidence of copy number variation in humans or other primates. They tentatively show that Neandertals have a bit more copy number variation than present-day humans, and identify a few loci with substantially higher copy numbers in one group or the other.
I recall in my own nathro days in college that was more of an open question … species or subpopulation, than it seems to have been more recently. Hawks holds puts us biologically in the same column. They are Homo sapiens, though he allows some paleontologists will disagree, based on morphological distinctions. But that, he notes, would make all non-Africans interspecies hybrids.
I kind of like the interspecies hybrid idea. It’s got an edgy sound to it. But Hawks also suggests that the 1 to 4 percent is only the currently discernable proportion. It could be higher, and sub-Saharan Africans could have some as yet undetected because it shows no variation from what we all have, part of the baseline, so to speak. I especially like his observation that genetically speaking, a minimum 1 percent Neanderthal genes in 5 billion people is the equivalent of 50 million Neanderthals “yawping from the rooftops,” which he suggests is not a bad genetic success rate for the Neanderthals. They weren’t evolutionary failures after all. Propagation of genetic material being the ultimate point of all our endeavors. Absent as yet is any indication of what discernable traits we might have inherited from them.
A lot of mind-bending aspects to this news. I’m good with it. I accepted being descended from slithering primodial bog sludge a long time ago. I mean one of those moments when you consider that, yeah, we have some successful molluscs and pretty nasty lizards to thank that we’re here, enjoying the good stuff. They lived and breathed, or whatever, just like us. More recent descent from thickset hairy low brows, that’s neither such a big surprise nor anything to sneer at. A delight that the mysterious, exotic strain known only through science and maybe vague mythic memory turns out, as Hawks says, not to have been a complete deadend. They live in us.
In fact, I was deliriously happy driving home tonight, thinking about all that grand and terrible prehistory. It’s not like anything’s changed with this news. It’s like a few years ago, when I was able to identify a location I had wondered about. The forgotten village in Kent where my father’s people … our Y chromosome … dwelt for centuries, down to the pub where they lived and poured beer, and the names of about 10 generations of them. It was like figuring out there are Saxons, Vikings, Celts and Picts up the line, and the ones who built Stonehenge, learning a little about who and what those direct barbarian forebears were. None of this past is that far in the past, after all. It all happened yesterday. And whenyou start to zero in on them, it’s a homecoming feeling: “There you are. I knew it.”
Ronald Bailey at Reason:
I will mention that my 23andMe genotype scan indicates my maternal haplogroup is U5a2a which arose some 40,000 years ago and were among the first homo sapiens colonizers of ice age Europe.
If you’re interested, go here for my column on what rights Neanderthals might claim should we ever succeed in using cloning technologies to bring them back.