Having looked at the genetic variations between us and our closest living relatives, the chimpanzees, and then at variation within our own species, we now turn to the tremendous breakthroughs that have been made in studies of the DNA of our close extinct relatives the Neanderthals. Twenty years ago, the idea that useful genetic data could be recovered from Neanderthal fossils to compare with our own sounded like science fiction, given the huge problems of extracting minute traces of DNA from ancient bones that had suffered from the effects of degradation, water, temperature changes, and soil acids for many millennia. Even if it was preserved (which seemed unlikely), it would be too difficult to find, too difficult to recover in large enough quantities to study, and too problematic to distinguish from all the other contaminating DNA that would also be there.
However, the field of ancient DNA did get off the ground in the early 1980s, with the sequencing of part of the mtDNA genome of the quagga, a recently extinct close relative of the zebra, whose skins survived in museum collections. And in 1984 a technique called the polymerase chain reaction (PCR) was discovered, which enabled researchers to produce millions of copies of specific DNA sequences in just a few hours. With this and improved recovery techniques and comparative DNA databases, it started to become possible to recognize and distinguish ancient DNA, where it survived in sufficiently large and well-preserved quantities. So in 1997 the recovery of the first Neanderthal mtDNA from the most famous representative of the group—the 1856 Neander Valley skeleton—caused a sensation. I was lucky enough to be asked to talk about the research at the press conference in London where Svante Pääbo announced the results, and I remember getting so carried away that I hailed it as an achievement comparable with landing someone on Mars! But for paleoanthropology it was a remarkable breakthrough, although things have moved on so fast in the last decade that over twenty Neanderthal fossils have now yielded this genetic material.
Because our cells generally contain hundreds or thousands of copies of the mtDNA genome, compared with the single set of autosomal DNA contained in each nucleus, and because the mtDNA genome was completely known by 1981, mtDNA was specifically targeted in early research on ancient DNA. But by 2006, using particularly well-preserved Neanderthal fossils and massive improvements in analytical techniques and computing power to recover and recognize small ancient DNA fragments, two international teams of scientists reconstructed the first large-scale genetic maps of the Neanderthal autosomal genome. Two fossil sites have proved particularly valuable in Neanderthal genome work, and in both cases their human remains may have resulted from cannibalism; in fact, there is speculation that defleshing the bones may even have helped the preservation of ancient DNA by heading off some of the proximate causes of DNA decay. One is the cave site of Vindija in Croatia, where small fragments of leg bones have by far and away the best preservation of Neanderthal DNA found so far, and the other is El Sidrón in Spain, which we discussed in chapter 4, and where great attention has been paid to recovering fossils with the minimum possibility of contamination by recent DNA.
The 454 Life Sciences company recently developed new instruments that allowed around 250,000 DNA strands to be sequenced in about five hours on one machine, and thus running several machines in tandem gave phenomenal improvements in recovery and recognition of the 3 billion pairs of chemical bases that originally made up the genome of these Neanderthal individuals. The 454 technique uses “shotgun” sequencing, in which DNA is chopped into huge numbers of short segments, and it is thus ideally suited for the tiny fragments of nuclear DNA required for ancient genome reconstruction. The old PCR technique was really only suitable for looking at longer fragments, such as in Pääbo’s early Neanderthal mtDNA work, but a development by the researcher Paul Brotherton and his colleagues called SPEX (single primer extension) now also holds great promise for the recovery of small fragments of the Neanderthal genome, in a more targeted approach than that of 454 analysis.
Genomic DNA in one of the El Sidrón individuals and another Neanderthal from Monti Lessini in Italy is providing some of our first glimpses of the constitution of southern European Neanderthals. They had mutations in the structure of a pigmentation gene, MC1R, which would have been expressed in red hair and pale skin, and despite the media reeling out a number of celebrities and sports stars with “ginger” hair, saying they were all “Neanderthals,” the more interesting story is that the Neanderthal variant was, in fact, distinct from that found in people of European descent today. Lighter pigmentation in humans has probably evolved for several reasons, but these include facilitating the synthesis of vitamin D in our skin under northern conditions of reduced sunlight. That at least some Neanderthals evolved their own depigmentation is not surprising when we consider that they were living in Europe for hundreds of millennia before modern humans did. What is surprising, though, is that if there was significant interbreeding between moderns and Neanderthals in Europe, potentially advantageous genes for lighter skin did not spread from them to us—and other research suggests that some of the gene variants that produce the light skin of many Europeans are probably less than 15,000 years old.
At least one of the El Sidrón Neanderthals had mixed genes at the TAS2R38 site, which in modern humans controls an ability to taste (or not taste) the bitter chemical phenylthiocarbamide (PTC). Related chemicals occur in leafy vegetables like Brussels sprouts and cauliflower, as well as in some poisonous plants, and it is possible that the tasting/nontasting dichotomy had evolved in more ancient humans as part of a balance between nutritional needs and detecting the danger inherent in some bitter and poisonous plants. At least two El Sidrón individuals also shared another genetic system with some of us, in the form of blood group O, which is coded on chromosome 9. The famous ABO blood groups are distinguished by the presence or absence of particular antigens on the surface of red blood cells, which give resistance to different diseases. In blood group O, a mutation blocks the action of an enzyme that produces the A and B antigens, and while this might seem to be disadvantageous, some disease agents actually lock on to the antigens, so that lacking them can confer an advantage. Chimps also have the ABO system, although group O is less common in them, so it seems likely that the system is a shared inheritance between chimps, us, and Neanderthals, with different diseases constantly pruning the patterns of individuals with the most vulnerable blood types. As more Neanderthals are sequenced, we will be able to compare their frequencies with those of humans today.
Carles Lalueza-Fox and his colleagues ingeniously also used the circumstances of the El Sidrón site, where a possible Neanderthal family group had become fossilized, to provide a glimpse of their social structure. The three men had identical mtDNA sequences, while the three women each had different sequences (but were related to three of the children), so if this really was a family group, it implied that the males were closely related and had probably stayed in their natal group, while the females had joined from other bands. Such exchanges of mates (perhaps mostly, but not always, peaceable) are important in reducing inbreeding and suggest that females were the predominant agents of gene flow, and perhaps also of any cultural transmission, between Neanderthal groups. This social system is known as patrilocality and is the most common in modern hunter-gatherers, and seems to be yet another behavior shared between Neanderthals and moderns.
A more controversial finding in two of the El Sidrón people was the presence of a gene also found in modern humans called FOXP2, which has misleadingly been called “the language gene”—as though only one gene is likely to be involved in this very human faculty. In fact this developmental gene became known through a kind of reverse engineering, because when it malfunctions in humans it leads to inhibitions in the comprehension and production of language, both in brain pathways and in the physical control of muscles concerned with the production of speech. When the gene was sequenced and compared between other primates and humans, it was discovered that there were two unique mutations in the human version, which had
presumably been selected to help facilitate our power of speech. Further research showed that it is at work in several areas of the brain concerned with cognition and language, and the human version of FOXP2 regulates (amplifies or moderates) the activities of more than a hundred other genes, whereas the “ancestral” version found in chimps has no such effect.
Our special version of the gene is not just about language, but it certainly does seem to be implicated in establishing neural pathways and the anatomical structures for speech. Thus there was speculation about whether Neanderthals would have possessed these same mutations, or, if lacking them, may also have lacked the capabilities of speech. The first drafts of the Neanderthal genome seemed to show the presence of the human form of FOXP2, but there were concerns even among the research team that this might be as a result of contamination from recent human DNA. However, the discovery of the “advanced” version in the carefully screened El Sidrón individuals seems to confirm its presence in these Spanish Neanderthals. So does this mean the Neanderthals must have had fully modern language? In my opinion, it does not, any more than the fact that the hyoid bones which sat in their throats were similar in shape to our own. But what is indicated is that we have no reason—from these elements of their biology—to deny them the potential for modern human speech capabilities. Whether they actually had our language abilities would also have depended on their own evolutionary pathway in behavioral complexity and the structure of the brain and vocal apparatus, as well as any evolutionary constraints that might have been at work from their distinctive anatomy.
An even more controversial issue than the presence or absence of the “modern” version of the FOXP2 gene in Neanderthals is whether they had a particular version of the MCPH1, or microcephalin, gene. In another case of reverse engineering, the action of this gene in humans became known through occasional failures in fetal development, where mutant versions seemed to be related to microcephaly (having an abnormally small head and brain). In such cases the faulty microcephalin gene apparently interfered with instructions for the production of neurons in the forebrain, leading to later deficits in the cerebral cortex. There are two main variants today, one most common globally (type D) and the other prevalent in sub-Saharan Africans (“non-D”). The genetic history of these two types appears to be quite distinct: while non-D seems to have developed in Africa and spread from there with the dispersal of modern humans, D has only proliferated in modern humans in the last 40,000 years, suggesting it has been selected as advantageous in at least some regions or situations. Yet the mutations in the genes show that these two types of microcephalin have deep and separate common roots going back over a million years, so where could the “new” D variant have come from? Attention focused on the Neanderthals as a possible source, implying that modern humans outside of Africa could have acquired their “young” variant from the Neanderthals, but sadly for this hypothesis, genome sequencing so far has shown that the Vindija Neanderthals possessed the ancestral “African” version of the microcephalin gene. Moreover, further research cast doubt on the whole scenario by failing to confirm the hypothesis that the microcephalin gene is strongly implicated in brain development, quality, and intelligence in “normal” humans. But the case of microcephalin does raise the issue that while mtDNA, Y-chromosome, and most autosomal DNA strongly support a recent African origin and subsequent dispersal for our species, there are variants of some genes that suggest a more complex evolutionary history for Homo sapiens.
Just as recent human DNA has been used to estimate past population numbers for Homo sapiens, so the small amounts of Neanderthal DNA recovered so far have also been subject to similar analyses, with clear and rather negative implications for Neanderthal viability. The complete reconstructed mtDNA genomes of six Neanderthals from Germany, Spain, Croatia, and Russia differ at only fifty-five locations out of a total of more than 16,000 base pairs, which is far less mtDNA diversity than in modern humans, and only a tiny fraction of the variability found in great ape species today. Estimates of population size from these data put the effective population size of Neanderthals across Europe and western Asia as low as 3,500 breeding females, although, as we have seen, that could translate into a much larger total number of people. In addition, they seemed to harbor a relatively greater number of potentially damaging mutations, which could have affected the structure of their proteins, something that often comes with smaller population sizes. Given that these were late Neanderthals sampled across much of their wide range, we can see how they could have been a threatened species even without the destabilizing impact of the arrival of modern humans in their home territories.
The partial Neanderthal genomes produced in 2006 contained some contradictory data, and doubts were soon expressed about whether the results were affected by remaining contamination from modern human DNA. Further investigations showed that this was indeed so, perhaps as much as 15 percent in certain areas. But now a composite and nearly entire Neanderthal genome has been drafted, providing rich data that promise yet more insights into their biology, from eye color and hair type through to brain quality and language skills. An international team of more than fifty researchers reconstructed more than 3 billion bits of DNA coding, again predominantly from three small fragments of bone from the Croatian cave of Vindija. These represented female Neanderthals who died around 40,000 years ago, and they have now been immortalized through their DNA. The results still largely confirmed the Out of Africa thesis, the overall distinctiveness of the Neanderthals, and a separation time from our lineage of about 350,000 years. But when the new Neanderthal genome was compared with those of modern humans from different continents, the results produced an intriguing twist to our evolutionary story because the genomes of people from Europe, China, and New Guinea lay slightly closer to the Neanderthal sequence than did those of individuals from Africa. Thus if you are European, Asian, or New Guinean, you probably have a bit of Neanderthal in your makeup.
One explanation is that the ancestors of people in Europe, Asia, and New Guinea 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 Homo sapiens for the genetic effect—greatly magnified as modern human numbers exploded—to be felt tens of thousands of years later. The amount of Neanderthal genetic input is estimated to be about 2 percent overall, a surprisingly high figure to me and other adherents of Out of Africa, who thought that any slight traces of interbreeding would have disappeared in the intervening years. Moreover, subsequent examination of six thousand worldwide modern samples by geneticist Vania Yotova and colleagues has revealed that non-African X-chromosomes have as much as 9 percent of Neanderthal-derived DNA in one particular location. What any of the shared DNA does for us, if anything, remains to be determined, but that will certainly be a focus for the next stage of this fascinating research. Alongside the apparent transfer of Neanderthal DNA into some of us, the comparisons also revealed more than two hundred genetic changes that we share to the exclusion of Neanderthals and chimpanzees. Some of these are in genes involved in brain functions, the structure of the skull and skeleton, the skin and its associated organs (such as hair and sweat glands), energy functions, and sperm activity.
These breakthroughs come at a time when renewed claims have been made that Neanderthals and early modern humans (Cro-Magnons) interbred in Europe about 35,000 years ago. Both fossil and DNA data indicate that the Neanderthals were a distinct lineage from modern humans, but a closely related one, and, as I explained, the level of morphological difference in the skeleton is comparable to that in recent primates and fossil mammals that demarcate distinct species. However, closely related mammal species may still be able to hybridize, so this was certainly possible between Neanderthals and Cro-Magnons.
The anthropol
ogist Clifford Jolly, who was my first teacher in paleoanthropology at University College, London, has made a special study of baboons and their relatives in Africa today, and these monkeys seem to represent distinct species groups in their appearance and behavior, yet when their DNA is analyzed, it is apparent that these “species” often exchange genes on at least a small scale, where they overlap geographically. As he said with reference to fossil human species such as the Neanderthals: “The message is to concentrate on biology, avoid semantic traps, and realize that any species-level taxonomy based on fossil material is going to be only an approximate reflection of real-world complexities.” I think we should certainly remember those wise words before we make any absolute statements about what might or might not have taken place if and when our forebears met the Neanderthals.
The essential question with regard to the behavior of our ancestors and the Neanderthals is, of course, did they regard each other as just another group of people? We don’t know the whole story, and the answer may have varied from one time and place to another, especially given the vagaries of human behavior. I take a different view on this than my friend Erik Trinkaus, who sees Neanderthal input in most of the earliest moderns in Europe, for example, in a child’s skeleton from the Lapedo Valley in Portugal. This fossil was buried with the red ocher and grave goods typical of many Gravettian burials (as discussed in chapter 4) about 27,000 years ago, and it has been described in detail, with contradictory indications. Nearly everything in its anatomy suggested that this was a fairly typical Cro-Magnon child, but the robusticity and proportions of its limbs and some of its dental features suggested to some that it represents evidence for admixture between Neanderthals and modern humans. Given its Gravettian age, apparently several millennia after the Neanderthals had vanished, the inference seems to be that this is a Cro-Magnon child that has retained some Neanderthal genes and characteristics from an earlier phase of interbreeding. However, in this and other cases, rather than perceiving features that definitely came from Neanderthals, I see some that were present in the ancestors of these modern people in their place(s) of origin, or that represent individual variations that overlap with those of the Neanderthals in some respects. When we have a reasonable sample of North African or Asian early moderns dating from about 50,000 years—the same period as many of our Neanderthals—we will be able to see what their morphology was, and we will be better able to determine whether features could have come from Neanderthal admixture or were due to ancestry in a different region.
Lone Survivors Page 22
