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paleoanthropology, genetics and evolution

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  • Denisova at high coverage

    Thu, 2012-08-30 15:25 -- John Hawks

    Science today has released the new paper on the Denisova high-coverage genome by Mattias Meyer and colleagues from Svante Pääbo's group [1]. There is a lot of material in the supplements of the new paper, and it will take some time to work through implications.

    The basics are quite simple: The paper confirms the initial interpretation of the genome by David Reich and colleagues [2] in most respects. The mixture with a whole-genome sample from Papua New Guinea is estimated at 6% Denisovan ancestry. Confirming the later paper by Reich and colleagues [3], the new analysis finds no significant evidence of Denisovan ancestry in a mainland south Chinese (Han Dai) individual, and can exclude it down to a very small fraction:

    However, in contrast to a recent study proposing more allele sharing between Denisova and populations from southern China, such as the Dai, than with populations from northern China, such as the Han (17), we find less Denisovan allele sharing with the Dai than with the Han (although non-significantly so, Z = –0.9) (Fig. 4B) (table S25). Further analysis shows that if Denisovans contributed any DNA to the Dai, it represents less than 0.1% of their genomes today (table S26).

    That is a mystery to be explained. How did Asians end up lacking any evidence of Denisovan ancestry, when the peoples of Sahul (Australia and New Guinea) have six percent? It's nutty! The early modern humans who were the ancestors of present Sahulian peoples surely came from Asia, and they surely mixed with Denisovans there somewhere, right? But today there's no sign that present Asian peoples descended from those early Asian peoples.

    We must, I think, conclude that there was at least one, and possibly several episodes of massive population movement across South and Southeast Asia.

    I have recently completed a review of the analogous problem for Neandertals in Europe -- late and early Neandertals themselves appear to have been a dynamic population. I'm now working on a review of the situation in Southeast Asia. We may fundamentally have to look at the archaeological record in a new, and much more dynamic, way than has been the case.

    Neandertal gene flow

    To me at the moment, this is the most interesting paragraph of the new paper:

    Interestingly, we find that Denisovans share more alleles with the three populations from eastern Asia and South America (Dai, Han, and Karitiana) than with the two European populations (French and Sardinian) (Z = 5.3). However, this does not appear to be due to Denisovan gene flow into the ancestors of present-day Asians, since the excess archaic material is more closely related to Neandertals than to Denisovans (table S27). We estimate that the proportion of Neandertal ancestry in Europe is 24% lower than in eastern Asia and South America (95% C.I. 12–36%). One possible explanation is that there were at least two independent Neandertal gene flow events into modern humans (18). An alternative explanation is a single Neandertal gene flow event followed by dilution of the Neandertal proportion in the ancestors of Europeans due to later migration out of Africa. However, this would require about 24% of the present-day European gene pool to be derived from African migrations subsequent to the Neandertal admixture.

    This is a very interesting result, partially because it is the opposite of what we are finding. As I explained earlier this year, we are finding Europeans to share more Neandertal alleles than Asians do. The difference in our results has been much smaller than 24%; really only an increase of less than 0.5% on the whole genome, or maybe 10% relative to the overall amount in Europe (which is on the order of 3%).

    My initial reaction to this difference is that it reflects the sharing of Neandertal genes in Africa. Meyer and colleagues filtered out alleles found in Africa, as a way of decreasing the effect of incomplete lineage sorting compared to introgression in their comparison. But if Africans have some gene flow from Neandertals, eliminating alleles found in Africans will create a bias in the comparison. If (as we think) some African populations have Neandertal gene flow, that probably came from West Asia or southern Europe. So as long as the present European and Asian (and Native American) samples have undergone a history of genetic drift, or if (as mentioned in the quote) they mixed with slightly different Neandertal populations, this bias will tend to make Asians look more Neandertal and Europeans less so.

    Anyway, this demands further investigation. The Denisova genome makes a more compelling outgroup for these kinds of comparisons, because it is much closer to us than chimpanzees are. But it isn't really an outgroup because it shares alleles by descent with Neandertals. So it takes some clever genetics to compare the distributions of derived alleles in these genomes in terms of introgression versus incomplete lineage sorting.

    Denisovan demography

    It has become possible to make some good estimates of demographic history using only a single diploid genome, using a technique developed by Li and Durbin [4]. Meyer and colleagues applied this technique to the Denisova genome, finding that its genetic history contrasts with that of living human populations:

    To estimate how Denisovan and modern human population sizes have changed over time we applied a Markovian coalescent model (22) to all genomes analyzed. This shows that present-day human genomes share similar population size changes, in particular a more than two-fold increase in size before 125,000–250,000 years ago (depending on the mutation rates assumed (23), Fig. 5B). Denisovans, in contrast, show a drastic decline in size at the time when the modern human population began to expand.

    There is not yet enough data from Neandertal genomes to apply the same method, but to the extent that we understand their diversity, they show a similar picture. These archaic humans in Eurasia had much, much smaller effective population sizes than the ancient population of Africa. That's not surprising, given what we understand about ancient hunter-gatherer population dynamics.

    What may be a bit more surprising is the geography. We know that Neandertals of Europe and Central Asia lived in an environment that was relatively marginal for their technology and subsistence pattern. The Denisovan population could well have lived in parts of South or Southeast Asia -- subtropical and tropical areas comparable to Africa in their ecological diversity and resource richness.

    We might have imagined that the Denisovan population would be more diverse than Neandertals -- that it might have been comparable in diversity to part of Africa, if not the entirety of Africa. The genome is inconsistent with that picture.

    How can we explain the apparent contrast?

    1. Maybe Denisovans didn't live in South or Southeast Asia at all. If not, that demands that we explain how Australians got their genes.

    2. Maybe the population was geographically extensive and diverse, but the genome from Denisova Cave doesn't represent it well. If so, we might discover that Sahulians actually have even more ancestry from this group. Alternatively, we might find that the early history of the population was widely shared, but the recent history diverged between Siberian and other branches of the Denisovan-inhabited region.

    3. Maybe African diversity emerged from a much more complex series of interactions than we now appreciate. The demographic model of Li and Durban doesn't encompass admixture, just the probability of gene coalescence across time. We have recently begun to appreciate the reality of ancient African population structure. If those initial African populations were more divergent from each other than Neandertals and Denisovans, their later mixture would give rise to a picture of early population expansion, even if each of them had relatively low (Denisovan-like) diversity.

    This picture is already complicated. It will get more so. We have a long way to go before the archaeology of MSA and Middle Paleolithic peoples will be reconciled with these genetic models.

    The "modern human" catalog

    I think it's tremendously interesting that the authors have compiled a list of gene variants shared by living humans that are absent from this high-coverage archaic human genome. It's a first step to identifying networks of genes that have been subject to recent evolutionary change in human ancestors.

    That being said, the list of genes itself doesn't lend itself to concrete conclusions:

    One way to identify changes that may have functional consequences is to focus on sites that are highly conserved among primates and that have changed on the modern human lineage after separation from Denisovan ancestors. We note that among the 23 most conserved positions affected by amino acid changes (primate conservation score ≥ 0.95), eight affect genes that are associated with brain function or nervous system development (NOVA1, SLITRK1, KATNA1, LUZP1, ARHGAP32, ADSL, HTR2B, CBTNAP2). Four of these are involved in axonal and dendritic growth (SLITRK1, KATNA1) and synaptic transmission (ARHGAP32, HTR2B) and two have been implicated in autism (ADSL, CNTNAP2). CNTNAP2 is also associated with susceptibility to language disorders (27) and is particularly noteworthy as it is one of the few genes known to be regulated by FOXP2, a transcription factor involved in language and speech development as well as synaptic plasticity (28). It is thus tempting to speculate that crucial aspects of synaptic transmission may have changed in modern humans.

    Interesting. I can imagine a Ph.D. dissertation looking into the function of each of those genes. It is surely true that in the last 300,000 years, human brains have been evolving. But why these genes as opposed to others? And how many regulatory changes (as opposed to amino acid changes) may have been further involved?

    Maybe even more interesting: How many times will the human alleles be found in some other Denisovan (or Neandertal) genomes, and how often will the "archaic" allele be found in anyone living now?

    A limited series of comparisons is too small to exclude that the range of variation will overlap, as fossil analysts have known for a long time. So we will need to work on extending our knowledge of the range of variation within living people, by increasing the sample of genomes representing populations around the world, particularly in Africa.

    The technology

    Of course, the most exciting thing about the new paper is the proof of concept for future high-coverage archaic genomes. The lab was able to generate the high-coverage sequence using its existing samples, by sequencing single-strand DNA instead of requiring double-strand DNA. This is a massive advantage when working with ancient DNA, because damage to the sequence often prevents double-stranded DNA from being amplified.

    The paper makes explicit that the Denisova phalanx simply has better endogenous DNA preservation than any other specimen known. That being said, the new sequencing method has greatly increased the sequence yield from the sample:

    We applied this method to aliquots of the two DNA extracts (as well as side fractions) that were previously generated from the 40 mg of bone that comprised the entire inner part of the phalanx (2, 8). Comparisons of these newly generated libraries to the two libraries generated in the previous study (2) show at least a 6-fold and 22-fold increase in the recovery of library molecules (8), which is particularly pronounced for longer molecules (fig. S4).

    It would be too soon to say that a similar increase in yield will happen for other specimens, but obviously, this may bring higher coverage into reach for several specimens that are currently only sequenced at very low coverage, including the Vindija, Mezmaiskaya, and El Sidron Neandertals. We will have to wait and see how the new technique affects ancient DNA recovery going forward.

    I keep telling people that I think it's exciting that research into human evolution is now pushing technology forward. It has often been that paleoanthropology uses technological advances in other fields. But with ancient DNA, we really see an organic growth of technology along with research questions about our evolution. In our work on the ancient genomes, we're making some progress pushing forward knowledge about human biology by understanding human evolution. Evolution really is the fundamental principle of biology, but using evolution to learn about biology sometimes requires traveling through time. Ancient DNA gives us a time machine bringing new insights into reach.


    References

    Synopsis: 
    A technological advance in library preparation gives rise to much better knowledge of the ancient Denisovans
  • Bones from the Torres Strait Islands

    Wed, 2011-11-23 09:07 -- John Hawks

    The BBC has an interesting article about the repatriation of skeletal remains from Torres Strait Islanders, held at the Natural History Museum, London: "Torres Stait islanders reclaim their ancestral bones". Along with detailing some of the ceremonial aspects of the return, there is a hopeful note about the future of research on these and other historically unique remains.

    Dr Richard Lane, former scientific director of the Natural History Museum and an architect of the agreement said that the islanders began warming to the idea of allowing the bones to be used for research as they learnt more about the work of the museum staff.

    "When we got talking in the pub, the islanders started asking us 'what is this DNA business and how can we use it to learn more about our history?'"

    The Torres Strait Islands are famous in anthropology as one of the earliest attempts to bring ethnographic, linguistic and biological study to a single research expedition (in 1898, carried out under the auspices of Cambridge University by A. C. Haddon and others). The expedition bears much similarity to "salvage ethnography" carried out within the United States in the early 20th century, in that the anthropologists were documenting practices and collecting materials that were endangered by Christian missionaries.

  • Denisovan DNA in the islands, and an Australian genome

    Thu, 2011-09-22 18:09 -- John Hawks

    David Reich and colleagues today report on the persistence of Denisova-like ancestry in island Southeast Asia and Australia (citation not yet available). Meanwhile, Morten Rasmussen and colleagues (citation not yet available) report on the whole-genome sequencing of hair from an Aboriginal Australian who lived some 100 years ago.

    The most obvious story: These data utterly destroy the hypothesis of a single out-of-Africa colonization of Southeast Asia by modern humans. Many human geneticists have argued our present pattern of diversity originated in a wave of successive founder effects coming from a single recent African origin. They were wrong.

    Instead, we can turn to a complex model with successive dispersals and episodes of population mixture. This is not a static model of isolation-by-distance; it is a dynamic model in which populations grow and spread across large spans of the Old World, again and again and again. By my count, at least three massive episodes of population dispersal and mixture are necessary in Reich and colleagues' model. A picture of their admixture hypothesis:

    Denisova admixture model from Reich et al. 2011

    This model depicts (a) an early divergence of an African (represented by Yoruba) and Asian/Australasian populations. These mix with first Neandertals and then (for the Australian/New Guinea/Mamanwa populations) with Denisova-like people. Later (b), after the initial habitation of the Philippines by the ancestors of Mamanwa, a population like Andamanese Onge pushes into the islands, mixing with the ancestors of New Guinea and Australian populations. Later still (c), a population ancestral to today's Chinese people mixes with Philippines and other Southeast Asian people.

    As complicated as it looks, even this model must be a vast oversimplification. I don't like or attribute much belief to mixture models like this, as they assume too much about relative population sizes and the timing of mixture. Many recent hunting and gathering populations of Southeast Asia are not included in the current samples, and the Chinese sample is itself the result of very recent demographic events, covering what once may have been a wider diversity of peoples. Depicting Australian and New Guinean populations as monolithic is an artifact of the small sample; these places themselves housed a tremendous diversity of peoples. Nevertheless, the true model won't be simpler than this one; it will involve many more events that the data cannot yet resolve.

    Hints of that complexity emerge from the Aboriginal Australian whole genome. Rasmussen and colleagues show that this individual shares some ancestry with East Asian peoples, but on the whole populations in Europe and East Asia are much more genetically similar to each other than to this genome. The picture from the whole genome is essentially the same as that drawn by the SNP comparisons by Reich and colleagues, but with the potential (in the long run) to actually trace the histories of individual genes. And I think the gene-by-gene account of history will be important, because we already have some evidence that a few Denisovan genes do persist in mainland Asia, even though most are gone.

    To explain why, we can look at the proportion of Denisovan ancestry in different populations as depicted in a map by Reich and colleagues. The pie charts are confusing here, because they report the fraction of ancestry from Denisovans in each population relative to the 5% estimate for New Guinea. So Australians also have 5% in this figure, Timorese have around 2.5%, and Bougainville has more than 4%.

    Notice the apparent lack of Denisovan ancestry in anyone who lives anywhere that was once connected by land with mainland Asia. I say "apparent" deliberately: Abi-Rached and colleagues reported last month on the widespread distribution of Denisovan HLA types among today's Asian populations, and those may well be products of Denisovan genes that were later selected. I've already identified a handful of other loci that seem to reflect Denisovan ancestry in mainland Asian people. According to the comparisons by Reich and colleagues, such loci must be exceptions.

    At the same time, the mixture model presents an important idea: Once there were people in Southeast Asia who had much more Denisovan ancestry than any populations still remaining today. Both Australian/New Guinea populations and Philippine populations like the Mamanwa have subsequently mixed with new immigrants who lacked any sign of Denisovan ancestry. Prior to this later mixture, the ancestors of those populations must have been more Denisovan -- Reich and colleagues estimate 7%. This is the first evidence that ancestry from archaic people of Eurasia was diluted to a lower value by later population movements. If the population mixture originally happened somewhere in mainland Asia, any traces of Denisovan ancestry in those areas has been diluted almost to nonexistence. But the persistence of some genes would be predicted if natural selection were maintaining them in the face of demographic pressure from elsewhere.

    About the Australian genome, there will be much more interesting analyses to come, I expect. As whole-genome data come to represent more of the variation within human populations, we get a larger store of information about how we came to be variable. Variation traces not only to population movements and demography, but also to natural selection. Australia's population history has been very different from many populations of the Old World, and this genome should give us new perspective on the effects of that demographic history.

    Synopsis: 
    The hypothesis of a single out-of-Africa dispersal is rejected by new data about Denisovan mixture and whole-genome sequencing of an Aboriginal Australian.
  • Repatriation in Torres Strait

    Wed, 2011-03-09 20:29 -- John Hawks

    The Guardian:

    Natural History Museum returns bones of 138 Torres Strait Islanders

    Tears of joy as human remains are repatriated to natives of islands located between Australia and Papua New Guinea

    Most, ranging from a jaw to full skeletons, have been in England since the mid 19th century. Some came back as sailors' souvenirs, some were collected by the surgeon of the British survey ship Rattlesnake, some were bought or traded among the first European visitors.

    According to the story, the bones are not to be reburied, at least not immediately, and may be studied by researchers in conjunction with Torres Strait Island natives.

  • 43,000-year-old assemblages from Highland New Guinea

    Fri, 2010-10-01 00:35 -- John Hawks

    Glenn Summerhayes and colleagues [1] enter a brief report in Science this week, describing radiocarbon dates for several small archaeological assemblages from the Ivane Valley, in eastern Highland New Guinea. The abstract:

    Data from the New Guinea Highlands (at an elevation of ~2000 meters) demonstrate the exploitation of the endemic nut Pandanus and yams in archaeological sites dated to 49,000 to 36,000 years ago, which are among the oldest human sites in this region. The sites also contain stone tools thought to be used to remove trees, which suggests that the early inhabitants cleared forest patches to promote the growth of useful plants.

    The details of the assemblages are illuminating:

    1. There are "waisted axes", large cutting tools with grooves on the sides for hafting onto wooden handles. They suggest, on ethnographic analogy, that these were used for forest clearing. I would imagine them useful for broader woodworking tasks, though, possibly including food extraction. The waisted axe artifacts here are not as extensively shaped as the later examples reported by Groube and colleagues [2]. The authors do not report on use wear for these.

    2. Starch grains adhering to some of the stone tools indicate yam utilization, but yams live quite a bit lower than the site where these tools were found.

    3. Lots of Pandanus nut roasting.

    The dates don't make a huge impact on our understanding of the chronology. Almost 25 years ago, Groube and colleagues [2] reported TL dates with a minimum of 38,000 years ago -- and a maximum around 56,000 -- for material remains on the nearby Huon Peninsula. The current study is consistent with the range of dates reported for that site, but pushes the minimum date earlier, to around 43,000 years ago (calibrated).

    The "Highland" aspect is more interesting, suggesting a fairly quick adaptability of early humans to a novel ecology. People had found the local plant foods in a unique ecology, they were exploiting a range of altitudes in their foraging activities, and possibly were altering their landscapes by forest clearing.

    Or possibly, all this suggests that humans had already been in the area for a substantial length of time...

    Or -- let me be even more subversive -- why is a New Guinea assemblage automatically assumed to be made by modern humans, when assemblages of equal (or greater!) technological sophistication on nearby Flores aren't?

    Just asking....


    References

  • Genyornis in Australian rock art?

    Thu, 2010-06-03 08:30 -- John Hawks

    Lots of cave paintings in Europe depict animals now extinct. Australian researchers have recently identified a rock painting as a depiction of the extinct thunder duck Genyornis:

    Scientists say an Aboriginal rock art depiction of an extinct giant bird could be Australia's oldest painting.

    The red ochre painting, which depicts two emu-like birds with their necks outstretched, could date back to the earliest days of settlement on the continent.

    ...

    Archaeologist Ben Gunn said the giant birds became extinct more than 40,000 years ago.

    OK, it's not strictly a duck, it's a stem anseriform. It could be the oldest painting anywhere.

  • What kangaroos do...

    Fri, 2010-04-23 11:07 -- John Hawks

    In the current issue of Heredity, Neaves and colleagues describe the results of their analysis of 12 microsatellite loci and the mtDNA of two kangaroo species -- western and eastern grey kangaroos. The two species are sympatric across part of Australia, basically a swath through western New South Wales. Neaves and colleagues describe substantial evidence for introgression of both autosomal loci and mtDNA into both populations:

    A total of 7.6% of grey kangaroos sampled from the region of sympatry displayed evidence of introgression. Although no F1 hybrids were identified, 14 M. giganteus backcrosses and 3 M. fuliginosus backcrosses were detected. In addition to introgression at nuclear microsatellite loci, a single individual also exhibited introgression of mtDNA. The two phenotypic groups apparent within the region of sympatry corresponded (in 95% of individuals) to the two clusters identified by genetic analyses. Furthermore, the two phenotypic/genetic groups within the region of sympatry corresponded to representative allopatric samples of M. giganteus and M. fuliginosus from elsewhere in the distribution. Five of the M. giganteus backcrosses identified by genetic analyses were classified as M. fuliginosus based on overall phenotype. Geographically, hybrids were located throughout the region of sympatry.

    This introgression has happened between the kangaroos despite the presence of prezygotic barriers that interrupt mating even in captivity:

    Physical differences in the structure of the cloacal eminence as well as the production of species-specific odours by females may allow for species recognition (Kirsch and Poole, 1972). These characteristic differences are potentially among the features that result in the unidirectional hybridization observed in captivity, with male M. giganteus frequently failing to recognize female M. fuliginosus in oestrus.

    In addition, there was male sterility in captive F1 hybrids. The authors expected a unidirectional bias in introgression owing to these factors, but the evidence says that gene flow apparently has gone both directions in the wild.

    Sort of interesting -- I would actually have expected there to be fewer postzygotic isolating mechanisms in marsupials because the placenta-uterus interaction isn't there complicating matters. But cases of interspecific hybridization have apparently been rarely noted -- maybe that's because Australia is small enough that phylogeographic differentiation doesn't go as far for large species. In any event, this case is another one where F1 hybrids are basically absent in the area of sympatry, yet substantial historical introgression has clearly happened. That's based on a restricted sample of 12 autosomal loci -- we would expect to see much more significant effects at a few genes if the introgressive variant had a high adaptive value.

    A model for ancient humans? Well, here's a case where 12 microsatellite loci seem sufficient to document substantial historical gene flow -- whereas in the human case described last week, there are more than 600 microsatellite loci to test the hypothesis. So the human case should have more power, all things being equal.

    But the humans probably don't have as simple a prior population structure. The kangaroos have two well-defined lineages with a large zone of sympatry. Ancient humans may not have been highly differentiated (given the low Neandertal-human mtDNA coalescence time, for example) and may not have had substantial zones of sympatry -- they may have been much more similar populations interacting along a narrow boundary or cline. So the phylogeography in humans will be much more subtle.

    References:

    Neaves LE, Zenger KR, Cooper DW, Eldridge MDB. 2010. Molecular detection of hybridization between sympatric kangaroo species in south-eastern Australia. Heredity 104:502-512. doi:10.1038/hdy.2009.137

  • Food notes

    Mon, 2009-11-16 15:47 -- John Hawks

    I'm laughing so hard it hurts:

    It's kind of embarrassing the way Australia puts itself out there as a barbecue-savvy culture, because you know what, we're crap.

    The end:

    [T]here might have to be a few fact-finding tours to Texas, and maybe Kansas City. I hear the barbecue is pretty good around those parts as well.

    Yes indeed.

  • Extinct marsupial lion in Australian rock art

    Tue, 2009-05-26 08:53 -- John Hawks

    Speaking of super-predators from the past, Natural History Magazine has a short article describing Australian rock art that may depict the extinct marsupial lion, Thylacoleo carnifex:

    Kim Akerman, an independent anthropologist based in Tasmania, says the painting unmistakably depicts a marsupial lion.

    It shows the requisite catlike muzzle, large forelimbs, and heavily clawed front paws. And it portrays the animal with a striped back, a tufted tail, and pointed ears.

    The image is described in a brief and readable report in the March issue of Antiquity.

  • Burrup rock art to be relocated

    Wed, 2008-12-24 08:30 -- John Hawks

    Paul Ham reports on developments which may force the relocation of rock art in northwestern Australia:

    The world’s oldest depiction of a human face could be threatened if Australian mining companies are permitted to build an explosives factory on the remote Burrup peninsula in the northwest of the country.

    A bulbous image of indiscernible sex, with huge eyes and sunken cheeks, the 10,000 year-old carving is chipped out of hard rock. Thousands of other carvings, mostly of plants and animals, which date back to beyond the last Ice Age, are scattered about the peninsula.

    Archeologists believe that aboriginal tribes made the distinctive carvings up to 30,000 years ago. They could be nearly twice as old as the Lascaux cave paintings in the Dordogne, France.

    The West Australian paper has this report on a December 20 rally:

    A rally in Perth today marked the 200th global 'stand up' for Burrup Peninsula with a renewed call for World Heritage listing for the rock art site.

    Since 2006, Friends of Australian Rock Art has organised 200 vigils for the Burrup rock art in more than 35 countries and in every continent except Antarctica.

    FARA spokesperson Robin Chapple said that international pressure was mounting for Australia to include the Burrup on the UNESCO World Heritage List.

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Neandertals

For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.

Denisova

From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.

Acceleration

The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.

Malapa

Just outside Johannesburg, the Malapa site is producing some of the most exciting finds in human evolution. This site is the headquarters of the Malapa Soft Tissue Project.