john hawks weblog

paleoanthropology, genetics and evolution

introgression

  • The Denisova genome FAQ

    Wed, 2010-12-22 12:35 -- John Hawks

    Today, a paper by David Reich and colleagues presents the nuclear genome of the Denisova pinky bone [1]. This is the second “whole genome” of an apparently extinct population of Pleistocene humans. This genome is nearly as distinct from Neanderthals as the draft Neanderthal genome is from living people.

    Between the draft Denisova genome, the draft Neanderthal genome, and the genomes of living people, we now have a record of three human populations that share origins relatively early in the Pleistocene.The paper presents some population modeling that attempts to estimate the divergence times and levels of gene flow among these populations. I think as a first effort these models answer some questions definitively, but leave substantial room for elaboration and improvement. There are many clear mysteries, most notably whether any known fossil samples can be attributed to the population represented by the Denisova sequence.

    The most significant finding in the paper is the demonstration that some living humans trace significant fraction of their ancestry to the population represented by the Denisova genome. As in the case of Neanderthals, different human populations show significantly different levels of similarity to the Denisova sequence. For Neanderthals, the similarities indicated between one and four percent Neanderthal ancestry for living people outside of Africa. In the case of the Denisova sequence, the greatest similarities are with living people in Melanesia – in this paper, represented by genome samples from Papua New Guinea and Bougainville. The similarities are consistent with approximately 4% contribution of a Denisova-like population to the ancestry of these living Melanesians.

    The paper estimates that together, the Denisova and Neanderthal-derived genes account for 8% of the ancestry of these living people.

    I find that estimate stunning, it's a huge contribution into living populations by these ancient Pleistocene populations.

    The paper additionally reports the mtDNA of a second individual from Denisova Cave, represented by an isolated third molar. This mitochondrial sequence is very similar to the sequence of the pinky bone, which I count as very important because it means there is potentially a population here. However, they do not report any nuclear genome results from this second individual.

    Those are the basic headline results. As I often do, I've prepared a series of frequently asked questions about the paper. This one is very dense with information content, and that includes 90 pages of supplementary information. We'll be working through it carefully during the next few weeks. The most exciting part is that, like the Neanderthal genome, these data will be available for other researchers to study. My lab has been intensively going through the Neanderthal genome with several hypotheses in mind, and we are eager to start working with the Denisova sequence.

    Could we have predicted this result?

    There were pretty clear hints that something interesting may have been going on with the population structure in the ancestry of living people in Papua New Guinea. My graduate student, Aaron Sams, has been looking into the hypothesis of a deeper Pleistocene component of ancestry in this population for the last few months. Of course we had earlier this year the announcement from Keith Hunley and Jeff Long's group that microsatellite variation was consistent with an ancient Pleistocene structure to the ancestry of Melanesians.

    Our notion here was that we could use ascertainment bias within the public sets of SNP data to look for deeper genealogical roots within some populations. Because most single nucleotide polymorphisms have been ascertained in Europeans, and secondarily within other populations represented in biomedical contexts or the HapMap – chiefly Africans and East Asians – there is a chance that a deep genealogical root in Melanesians might be obviously represented by a haplotype bearing all ancestral polymorphisms. That's not to say that the population is more ancestral than other populations, just that the unique derived variants in that population were not ascertained.

    By targeting these regions with all-ancestral haplotypes, we began to make substantial progress identifying regions as candidates for a more ancient population structure in this part of the world. Pretty exciting stuff in the absence of an ancient human genome. But now the Denisova sequence gives us a very clear sign that such regions should be very widespread across the genome. Some of them are presently at high frequencies within samples of PNG genetic variation, so there is a good chance that some variants will turn out to be of adaptive importance in this population.

    The point is, this result doesn't come from nowhere. It was clearly anticipated by analysis of the genetic variation within living Melanesians. It is perhaps a bit of a surprise that an ancient genome from southern Siberia would provide so many genealogical ties to this island population. That will require us to give some close consideration to the population structure of Pleistocene people as well as the migration history leading to the peopling of Oceania.

    What is this tooth?

    The paper identifies the tooth as an upper third molar, or possibly as a second molar. What we can say about it is that it's relatively large. In fact its length and breadth put it within a size range occupied by australopithecines and early Homo, both H. habilis and H. erectus. There are no distinctive morphological characters that would allow it to be assigned to any taxon.

    What the paper doesn't point out is that there are Upper Paleolithic specimens that equal or exceed this tooth in size. For example, the measured length and breadth of an upper second molar from Oase, Romania, are larger than this specimen, and the third molar (in the crypt) of that specimen is yet larger. There is an Upper Paleolithic-associated molar from Turkey which is also exceedingly large.

    I don't take that as a sign of relationship between this specimen and early Upper Paleolithic people -- even though these are some of the earliest. It is another sign of how non-diagnostic this tooth actually is. I would say that in the absence of genetic information, we'd be looking at these remains as likely early Upper Paleolithic people, and accentuating these similarities.

    With the genome, there's a tendency to assume a completely opposite attitude -- that they must represent something separate and different from Upper Paleolithic people. That may be an overreaction -- the evidence of gene flow suggests the possibility of continued interaction among these Late Pleistocene groups.

    What happened to the X-Woman?

    I guess when they found a second individual, it was better to have a name for the group rather than the individual. Or maybe somebody didn't like the name X-Woman. As in, "I wonder what happened to the Oneders".

    Anyway, the paper uses the term "Denisovans" for this ancient population. That implies a certain agnosticism about whether any particular kinds of fossil humans might belong to the same population as the two sequenced individuals.

    How were the Denisovans related to Neandertals?

    Remembering that the Neandertal draft genome contains a very high fraction of spurious unique changes, Reich and colleagues performed a similar series of statistical comparisons to those done by Green and colleagues in the Neandertal analysis. Most prominent is limiting the comparison to places where humans and chimpanzees are known to differ. By targeting these sites, the analysis cuts the rate of false positive changes to a manageable level.

    I mention that because it is necessary to make sense of the direct quotes:

    The Denisova genome diverged from the reference human genome 11.7% (CI: 11.4–12.0%) of the way back along the lineage to the human– chimpanzee ancestor. For the Vindija Neanderthal, the divergence is 12.2% (CI: 11.9–12.5%). Thus, whereas the divergence of the Denisova mtDNA to present-day human mtDNAs is about twice as deep as that of Neanderthal mtDNA, the average divergence of the Denisova nuclear genome from present-day humans is similar to that of Neanderthals.

    So the Denisova, Neandertal and human genomes are close to a trichotomy in terms of their average relationship. For any particular gene, of course, there may be sister pairings between any two of those three -- and in many cases, between Denisovans and some living humans to the exclusion of other living humans. This gives rise to several tricky statistical issues as we consider particular gene loci.

    For the moment, we'll consider the genome-wide average. How similar are Denisovans and Neandertals? Reich and colleagues considered the subset of sites where two sequences (out of Denisova, Neandertal and human) share a derived SNP variant:

    The number of sites where the Denisova individual and Neanderthal cluster to the exclusion of the Yoruba and chimpanzee is 46,362, compared with an average of 22,012 sites for the other two possible patterns (Yoruba and Denisova, or Yoruba and Neanderthal). This excess of sites where Denisova and Neanderthal cluster supports the view that the Denisova individual and Neanderthals share a common history since separating from the ancestors of modern humans (Supplementary Information section 6).

    They share twice the number of derived variants compared to the human in their comparison. Denisovans and Neandertals shared substantial ancestry with each other. That may mean they emerged from a single population -- possibly the early Middle Pleistocene population of Eurasia. Or it may mean that they exchanged genes after they reached Eurasia.

    Reich and colleagues address this issue further by comparing pieces of two Neandertal genomes with Denisova. The Mezmaiskaya specimen is represented by much less sequence than the Vindija draft genome but it is geographically intermediate between Croatia and Denisova. By including this specimen with the Neandertals, Reich and colleagues could do a statistical analogue of FST -- giving a way of examining the extent of genetic exchanges between the ancestors fo these Neandertals and Denisovans. They found that the Mezmaiskaya and Vindija specimens were much more likely to share alleles with each other than with the Denisova sequence. It's a striking statistic -- if you do the same comparison with living people, they're 10 percent or so more likely to share alleles with neighbors than with distant individuals; Neandertals were apparently 65 percent percent more likely to share alleles with each other than with Denisova. It's not an exact stand-in for FST, but it's nearby. This was a highly structured Pleistocene population.

    Is the nuclear variation consistent with the mtDNA?

    I wrote about the Denisova mtDNA sequence last spring ("The Denisova mtDNA sequence: The X-Woman"). The sequence is an outgroup to a clade including both humans and Neandertals, and appeared to branch from our ancestors roughly a million years ago. That appeared to be a very interesting date -- possibly consistent with Homo erectus, but too recent to reflect the first dispersal of Homo from Africa, more than 1.8 million years ago.

    That mtDNA divergence date was not easily interpreted. As I pointed out at the time, it might have been consistent with incomplete lineage sorting in a single widespread human population -- maybe even the Neandertal population.

    Reich and colleagues show that the mtDNA divergence between Denisova and the modern-Neandertal clade is deeper than expected given the nuclear genome genealogical divergence. They also show that the nuclear genomes of Neandertals and Denisovans are somewhat closer than either is to the majority ancestors of living people. They discuss two possible explanations.

    One scenario a mixture of the Denisovans with a more ancient Pleistocene population, followed by introgression of a more ancient mtDNA clade into the Denisovans. This would assert an ancient structured population preceding the origin of Denisovans, presumably from one of the Middle Pleistocene populations of Africa or Eurasia.

    A second scenario is incomplete lineage sorting, in which an earlier mtDNA divergence was captured by the Denisova and Neandertal populations at the time of their divergence and differentially lost from them.

    Reich and colleagues show that both these scenarios may be consistent with evolution by genetic drift in these ancient groups, given some assumptions about their population sizes.

    I think there are still some reasonable questions about the relative dates of divergence, but those can probably be answered by considering the full pattern of variation of genealogies across the genome. Additionally, there may be uncertainty about the mutation rates used in both the mtDNA and nuclear comparisons. That's one reason why I consider the population models here to be a first draft of the real history.

    What are the archaeological associations?

    The current paper is more clear about the site's dating and stratigraphy than the earlier, shorter paper by Krause and colleagues [2]. In the spring, it appeared that the pinky bone was associated with the Upper Paleolithic at the site. In the current paper, the authors explain the complexity of layer 11, which contains both Upper Paleolithic industry and these skeletal and dental remains:

    The small size of both the phalanx and the tooth precludes direct radiocarbon dating. We instead dated seven bone fragments found close to the hominin remains in layer 11 in the east and south galleries. To ensure that they were associated with human occupation of the cave we chose bones that have evidence of human modification, including a rib with regular incisions and a bone projectile point blank generally associated with Upper Palaeolithic cultural assemblages. In the south gallery, where modified bones were not available, we used herbivore bones (Supplementary Information section 12).

    Four of the seven dates are infinite dates older than 50,000 years BP (uncalibrated), whereas three are finite dates between 16,000 and 30,000 years BP (Supplementary Table 12.1). The rib with incisions and the projectile point blank are about 30,000 and 23,000 years BP, respectively. Together with three previous dates23 this shows that layer 11 contains cultural remains from at least two different time periods, one period older than 50,000 years BP and one more recent period. However, the stratigraphy is complicated by the discovery of a wedge- shaped area close to the area where the phalanx was found that is likely to be disturbed (Supplementary Information section 12). Hominin remains large enough to allow direct radiocarbon dates may even- tually be discovered in the cave, but a reasonable hypothesis is that the phalanx and molar belong to the older occupation.

    So, no direct dates. By inference (of their weird-looking genetic sequences), the two skeletal individuals are likely to be older than the Upper Paleolithic, but the stratigraphy does not require this. There is a mixing of older and younger materials.

    Adding to the problem, the finger bone has anomalously good preservation of DNA -- the authors point out in the first paragraph of the discussion:

    The molecular preservation of the Denisova phalanx is exceptional in that the fraction of endogenous relative to microbial DNA is about 70%. By contrast, in all Neanderthal remains studied so far the relative abundance of endogenous DNA is below 5%, and typically below 1%. Furthermore, the average length of hominin DNA fragments in the Denisova phalanx is 58 base pairs (bp) (SL3003) and 74 bp (SL3004) in spite of the enzymatic treatment that removes uracil residues and decreases the average fragment size, whereas in most well-preserved Neanderthal samples it is 50 bp or smaller without this treatment. Thus, although many Neanderthals are preserved under conditions apparently similar to those in Denisova Cave, the Denisova phalanx is one of few bones found in temperate conditions that are as well preserved as many permafrost remains. It is not clear why this is.

    They can rule out some explanations because the molar does not have the same exceptional preservation. At the moment, we can probably just chalk it up to good luck. But I think the issue is not irrelevant to the problem of dating. What is going on with this site? Very unusual.

    Why Melanesians?

    Denisova Cave is in southern Siberia. The hominin occupation of the cave appears to have been within the last 50,000 years. People reached Sahul sometime before 40,000 years ago. How in the world did these people come into contact?

    The most plausible hypothesis is that the Denisovans represent a much larger and more widespread population across South and Southeast Asia. A population dispersing in the direction of island Southeast Asia would have encountered and mixed with this population. The dispersing population would have absorbed some adaptive genes, which would have increased in frequency thereby increasing the apparent genetic contribution of the indigenous Pleistocene population.

    This leaves some unanswered questions.

    1. Who were these ancient people? Were they "Homo erectus"?

    This would be my null hypothesis -- that we are looking at one site representing a widespread population across the eastern extent of Eurasia, including Sundaland, during the Middle Pleistocene. However, this scenario is not fully consistent with the population model presented by Reich and colleagues. In particular, they derive Denisovans and Neandertals from a single ancestral population that diverged from humans sometime during the last 500,000 years. That means that the type specimen of Homo erectus (roughly a million years old) cannot possibly have been part of the Denisovan population. Most of the fossil record of Homo erectus in Asia is too old to have been part of a Denisovan population.

    2. Why do the other populations of East and Southeast Asia not show clear signs of mixture with the Denisovans?

    The statistics in the paper show a clear (and large) component of Denisovan ancestry in the PNG and Bougainville genomes, but no large component elsewhere in Asia. Reich and colleagues address this question briefly.

    An interesting question is how widespread Denisovans were. A possibility is that they lived in large parts of East Asia at the time when Neanderthals were present in Europe and western Asia. One observation compatible with this possibility is that Denisovan relatives seem to have contributed genes to present-day Melanesians but not to present-day populations which currently live much closer to the Altai region such as Han Chinese or Mongolians (Table 1). Thus, they have at least at some point been present in an area where they interacted with the ancestors of Melanesians and this was presumably not in southern Siberia.

    Probably the best explanation for the disproportionate impact of the gene flow into the ancestors of Melanesians is a kind of peninsula effect -- they encountered these people early, moved along through their population the furthest, and acquired a substantial signature by a combination of selection and "surfing" neutral alleles along with population expansion. We can assume, I think, that Melanesians are not unique. We do not have a substantial genetic representation of island Indonesia or Australia in these comparisons, I would expect they trend in the same direction. Also, Melanesian-derived genes make up a large component (upwards of 20 percent) of the nuclear genome of Polynesians today. This is a large population of people with Denisovan genes, in other words.

    But why not China? Why not South Asia? These are extremely interesting questions. Were the Denisovans not present in China -- was there possibly yet another Pleistocene population there?

    Why not call them "Homo erectus"?

    Formally, we don't know whether the individuals represented by these genetic samples would have had the diagnostic features of Homo erectus. They don't live especially near the main samples of Homo erectus, and they lived long after the main samples of Homo erectus appear to have existed.

    But worse, as I indicated above, there are serious inconsistencies between the fossil record and the population model presented by Reich and colleagues.

    1. "Homo erectus", as usually understood, occurred widely in Asia, including China and Java, and Africa during the span from 1.95 million to 750,000 years ago. In China and Java, fossils attributed to Homo erectus persisted until 200,000 years ago. There is no unequivocal fossil of Homo erectus after 200,000 years ago (including some not-yet-published redating). I'm obviously glossing many complexities in that description, but trying to pose the species in the broadest possible geographic and temporal range.

    2. Green and colleagues [3] derived Neandertals from a common ancestor with living Africans only 250,000-400,000 years ago. A model including the Denisova data is provided in the current paper. It has wider confidence limits and reports the answers in generations. If we assume 20-year generations, the current paper puts the emergence of a Neandertal-Denisova clade at between 190,000 and 520,000 years ago, and the divergence of the Neandertal and Denisova branches around 50,000-100,000 years later.

    In other words, possibly sometime after the time of the last unequivocal H. erectus fossils, the Denisovan population was diverging from Neandertals. These events occurred more than a half million years after the Trinil individual -- type specimen of Homo erectus -- lived.

    3. Millions of living people have their ancestry in these Pleistocene populations. That tends to make their identification as different species somewhat problematic. Even if we could identify the Denisovan population with the fossil evidence of Homo erectus, maybe they don't merit that species-level distinction. Or maybe we should recognize two or more distinct populations within what we now call Homo erectus.

    And before you splitters out there get excited -- these would not be the same two populations (H. ergaster and H. erectus) currently promoted by some paleoanthropologists. That issue is way too early to be consequential in the current context.

    Some of these issues can be solved by altering the population model. For example, if we assume a slower mutation rate (consistent with comparisons between parents and offspring in living people), the estimated divergence times will be much higher, possibly consistent with a widespread population at the time of Zhoukoudian or Sangiran. It's not obvious that this would fully bring the genetics into accord with the fossil record, but it would eliminate many inconsistencies.

    What drives you crazy about this?

    Well, it's obviously very exciting, but I find it very difficult to talk about these Pleistocene populations without falling into bad habits.

    Our common ancestry as humans goes back to the Early and Middle Pleistocene. The (now multiple) Neandertal genomes and the Denisova genome share genes with some people and not others because of this common ancestry.

    In addition, some living people carry even more genes from Neandertals because they have an appreciable fraction of Neandertal ancestry. That makes it nonsensical to talk about "Neandertals and the ancestors of modern humans". Neandertals are among the ancestors of modern humans.

    Just so with Denisova. It's nonsensical to talk about a three-way split between Neandertals, Denisova and modern humans. We can talk about a population model with a clade separating an ancestral Neandertal-Denisova population from contemporary Africans.

    I have to remind myself again and again when I talk to people about these issues that "modern human ancestors" is not a group that excludes these Pleistocene people.

    Once we put ourselves into the mode where we are referring to a population model, it is important to recognize the limitations of those models. For example, we cannot presently exclude many kinds of gene flow among these Pleistocene populations. We can understand some limits to the level of gene flow -- these populations were highly structured, it wasn't Pleistocene panmixia. But it is premature to talk about isolation without recognizing the limits of our ability to test these population models.

    The difficulty with terminology tells us something very important. A large-scale reorganization of the science of human origins is upon us. The terms we are used to using will, many of them, become obsolete. Some now-obscure terms will become very important.

    We might think the new terms are likely to be technological -- but I think that the technology is changing too fast for that. Most people won't need to learn the ins and outs of a particular sequencing platform, because in two years it will be obsolete.

    No, much more important is our way of talking about the relations of biological and cultural evidence. What does an archaeological pattern mean, and how does it relate to biological connections between populations? How can we identify the genetic causes of skeletal and dental phenotypes? What is the importance of a morphological or phylogenetic species in the context of these clear signs of genetic intermixture?

    Many of these are old questions. They are about to get new answers, addressed in a new way using new evidence.

    References

    1. Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PLF, et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature [Internet]. 2010;468:1053–1060. Available from: http://dx.doi.org/10.1038/nature09710
    2. Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Paabo S. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature [Internet]. 2010;464:894–897. Available from: http://dx.doi.org/10.1038/nature08976
    3. Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, et al. A Draft Sequence of the Neandertal Genome. Science [Internet]. 2010;328:710–722. Available from: http://dx.doi.org/10.1126/science.1188021
    Tags: 
    Homo erectus
    Melanesia
    Neandertals
    population structure
    Denisova
    introgression
    Neandertal DNA
    out-of-Africa
    Synopsis: 
    A genome from the Altai is revealed as a representative of an ancient hominin population new to science.

  • Divergent MHC alleles in domesticated sheep

    Sun, 2010-11-28 09:47 -- John Hawks

    I know, what an exciting headline!

    I've written quite a bit about the origins of domesticated cattle and introgression among the species of wild cattle giving rise to the current pattern of genetic diversity. I'm keeping track of that area because the process of domestication and subsequent interaction of domesticates with their wild relatives provide one kind of natural model for the interaction of ancient human groups such as the Neanderthals. We used these examples in our 2006 paper [1].

    Cattle have been a convenient example because there has been a lot of genetic work on them, and they have multiple wild species that diverged early in the Pleistocene. But other domesticates are also intense targets of sequencing and genome discovery, and as we understand more about their variation, we are beginning to find interesting patterns. Going through my notes today I found an interesting paper on sheep MHC polymorphisms [2]:

    Trans-Species Polymorphism and Selection in the MHC Class II DRA Genes of Domestic Sheep

    Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries). We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201) differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901), which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the induction of protective immunity.

    That probably deserves more thought and explanation that I can give it right now. As the authors point out in the paper, sheep domestication was a complicated process:

    The complex origin of domestic sheep is apparent from the presence of at least five distinct mitochondrial lineages [20], some of which cannot be traced to a wild ancestor [24], [25]. This diversity is likely to originate from geographically isolated subspecies of wild sheep that have hybridised as a result of human migrations over the 8–10 millennia since the initial domestication events in the Near East and Asia [26]–[28]. Frequent hybridization events are likely to have occurred between domesticated and local wild populations providing the high levels of MHC diversity evident in present day domestic populations as well as a degree of resistance to endemic disease and adaptation to local environmental conditions [29].

    Their interpretation of an ancient selective balance, retained in domesticated sheep from very distant common ancestors with oryx, probably is the most likely scenario. But I think this provides a nice example of how difficult it is to tell ancient balanced polymorphisms apart from relatively recent hybridization. That's a problem that we continue to face with interpreting human and Neandertal genetic variation.

    Also the case illustrates how important is the mixture of different wild populations in the origin of domesticates. Even if a wild population makes up a very small fraction of the genetic heritage of the current domesticated species, one or more adaptive loci from that population may nevertheless be very important to the survival and success of the later species.

    Genes don't care where they came from, and their function is not irrevocably marked by their origin.

    References

    1. Hawks J, Cochran G. Dynamics of Adaptive Introgression from Archaic to Modern Humans. PaleoAnthropology. 2006;2006:101–115.
    2. Ballingall KT, Rocchi MS, McKeever DJ, Wright F. Trans-Species Polymorphism and Selection in the MHC Class II DRA Genes of Domestic Sheep. PLoS ONE [Internet]. 2010;5:e11402+. Available from: http://dx.doi.org/10.1371/journal.pone.0011402
    Tags: 
    immune
    domestication
    non-primate
    introgression

  • Ozzy Osbourne, archaic human

    Mon, 2010-10-25 16:28 -- John Hawks

    Via a reader: The Daily Mail really aims for the lowest common denominator of genetics: "We've all suspected, now it's official: Ozzy Osbourne IS a Neanderthal"

    He claims his ‘superhuman’ genes have kept him healthy despite a lifetime of rock ’n’ roll excess.

    And now it seems science may back up Ozzy Osbourne’s theory that he has a particularly hardy family tree.
    Researchers studying his DNA have found that the singer is the descendant of a Neanderthal man.

    This is almost an entry in the Neandertal anti-defamation series. What holds it back is the clear involvement of some shady genetics company. Get this:

    The researchers also examined the gene the body uses to break down alcohol and discovered an ‘unusual variant’ which could have helped Osbourne survive during the years when he drank up to four bottles of Cognac a day.

    ‘Given the swimming pools of booze I’d guzzled over the years – not to mention all the [drugs] – there’s really no plausible medical reason why I should be alive,’ he told The Sunday Times.

    What a crock! I mean it's one thing to tell people their genomes have Neandertal markers. I mean, that's a crock, too, since we have no clear marker list yet. But at least it's a harmless entertainment-only kind of a crock.

    Now, when you tell an alcoholic that he has an "unusual variant" that "could have helped" metabolize alcohol better -- that's an altogether deeper level of crockery.

    I know, it's like the "Weekly World News", but cheez Louise, what a crock!

    Tags: 
    celebrities
    ethics
    admixture
    Neandertal DNA
    introgression

  • Quote: Boyd on New World pigmentation clines

    Tue, 2010-09-28 16:44 -- John Hawks

    I'm using some statistics out of William Boyd's 1956 printing of Genetics and the Races of Man[1]. It gives a good accounting of blood group data known more than fifty years ago, which I'm using to illustrate my intro lectures. Meanwhile, there are some interesting passages, from the standpoint of today's knowledge of the human genome and its variation.

    On skin pigmentation -- this is the earliest statement I've run across of the argument that the New World pigmentation cline is shallower than the Old World cline because of the relative recency of occupation (pp. 178-180):

    The aborigines of the New World, though not by any means identical, agree in having on the whole considerable skin pigmentation. If pigmentation is adaptive, and conforms to climate, why are not the Eskimo and the inhabitants of Tierra del Fuego as light as Europeans? This looks like a considerable difficulty, but the solution is probably comparatively simple. The aborigines of the New World have not been here for more than about 25,000 years, or about 1000 generations. They are by origin Asiatic, and in Asia skin pigmentation is fairly heavy. Unless the selection of light skin as opposed to dark were fairly intense, the time elapsed has simply not been enough to allow for much adaptation to occur (12). As a matter of fact, the populations which might have been expected to become lighter, namely the Fuegans and the Eskimo, have probably had a shorter time in which to achieve this end than other American aborigines, for it is reasonable to suppose that the Fuegians did not reach their present home until long after their northern neighbors were well installed. And all students of the Eskimo agree in recognizing them as probably the most recent (aside of course from the whites) arrivals in America. It could well be that there has just not been enough time for selection to bleach the skins of the American aborigines.

    Reference 12 is Haddon's Races of Man, which I have requested from the library.

    I'm following up, because skin pigmentation is one of the traits most clearly subject to recent rapid selection. The new mutations that lighten skin tone in Europe and Asia are only partially shared between those populations. Many alleles are very common in one population, but nearly absent in the other. So far, the estimates of dates for these new variants are all within the last 20,000 years, but many remain undated. So we can't specify the level of pigmentation of people 15,000-20,000 years ago, yet, but it would have been substantially darker than those populations today.

    Which leaves us with the same question, but from the opposite perspective. We now know that pigmentation evolved rapidly in Eurasia, the strong gradient of pigmentation having increased greatly within the last 20,000 years. We also know that the occupation of temperate South America began quite early, with people having been there longer than 10,000 years. So why did the New World end up with a more gradual cline -- darker pigmentation in the temperate and Arctic regions, lighter in the tropics than in the Old World? Was selection less intense? Can we attribute the difference to demography? Or chance?

    Boyd next alluded to a demographic explanation -- low population density:

    In any case, the pre-Columbian population was so sparse compared with that of Asia and India that on a statistical basis alone we should be justified in asserting that skin pigmentation conforms to climate.

    Them's some tricky statistics.

    We would of course today recognize that the sheer number of people is not especially relevant; much more powerful is the independent occurrence of a similar response in two long-separated populations. But Boyd was concerned with a different issue: Some had been claiming pigmentation as a neutral trait, making it more useful as a race marker:

    This has been denied chiefly by those who were concerned to prove skin color a non-adaptive character, so that it might safely be used in the classification of races (12). Since the more up-to-date students of anthropology have given up the idea of relying on non-adaptive characters, or even believing that any such exist (13), there is no longer much dispute about the probable adaptive value of skin color (emphasis added).

    Well, makes me glad to be an "up-to-date" student! There in fact has been an ongoing debate about "non-adaptive characters" as concerns the relationship of Pleistocene people. Many geneticists were surprised to discover the persistence of Neandertal genes, but in fact the skeletons of Upper Paleolithic Europeans clearly bear Neandertal traits. The debate for the last 30 years hasn't been chiefly about the presence of these traits, but instead about whether they were adaptive. Some argued that adaptive traits were not suitable evidence for a relationship, because they could emerge by parallelism in distinct populations.

    Others observed that adaptive traits were more likely to be shared among populations linked by gene flow.

    Now, of course, we have remaining unanswered questions about these shared traits. The shared traits are clearest between Upper Paleolithic Europeans and European Neandertals. We don't have genetic information yet telling us about the extent of Neandertal gene sharing with these early Europeans. Was it more than elsewhere? The traits would argue for it.

    What about the Neandertal genes in populations far from Europe? One might expect Neandertal-like morphology to show up at some low level. Of course morphological features are polygenic, so that phenotypic resemblance falls much faster than genic identity. And Holocene populations have continued to evolve. Maybe early Asian skeletal remains like the Upper Cave skulls (ca. 11,000-20,000 years old) actually reflect that Neandertal heritage to a greater extent than recent samples.

    Then there is the likelihood of other contributions, more local ones, to later populations.

    Returning to the topic of pigmentation, many of us used to assume that the light skin of Europeans in part reflects Neandertal ancestry. That is, just as Boyd suggested, it would have taken a lot longer than 25,000 years to get the current strong cline of skin pigmentation in the Old World. If you could have longer, getting lighter pigmentation from earlier inhabitants of Europe, for example, you could explain a stronger cline with the same strength of selection.

    I no longer think this is necessary. It's still possible that we got some pigmentation variants from Neandertals, but we haven't found any yet. And we've been looking. It does seem that Neandertals had some of their own pigmentation variants. Maybe we'll find many more of those, maybe not.

    References

    1. Boyd WC. Genetics and the Races of Man. Boston: Little, Brown and Company; 1956.
    Tags: 
    quotes
    introgression
    Zhoukoudian
    America
    pigmentation
    recent selection
    Neandertal DNA
    China
    American Indians

  • "Neandertal stimulation": Weckler and biogeography

    Sat, 2010-09-25 14:27 -- John Hawks

    I'm reviewing some old viewpoints about the relationships of Neandertals and other peoples. These include mainstream opinions that persisted over decades as well as more idiosyncratic ideas. This is mostly pre-1960 stuff for the time being.

    To the extent that old ideas are wrong it is no surprise: Science progresses by rejecting wrong ideas, and paleoanthropologists of the past lacked the luxury of today's data. To the extent that the ideas look familiar, they remind us that our current hypotheses in many instances echo ideas that were advanced fifty years ago or more.

    Weckler's model

    A bit off the mainstream was a paper published by Joseph E. Weckler [1], titled "The relationships between Neanderthal Man and Homo sapiens." Weckler was a cultural anthropologist who had done fieldwork in the American Southwest and the South Pacific [2]. He wrote only one paper on Neandertals but this received substantial attention, first published in the American Anthropologist and later revised in a simplified version for Scientific American. Weckler was very interested in the migration and dispersal of ancient populations, maybe because of his work on the ethnography of the South Pacific. He brought that perspective to the Neandertals and other ancient groups.

    Weckler saw Pleistocene human population dynamics as having been directed by glaciations and geographic barriers. In general, Weckler thought that the pre-modern population had been divided into allopatric species or subspecies. These groups would have been isolated from each other much of the time, but occasionally thrust back into contact by shifts in the climate. During glacial phases, Weckler posited that Europe and Asia north of the Caucusus-Himalaya axis would have been uninhabitable. During warmer interglacials humans moved into these northern areas, where water and mountainous barriers tended to isolate them. The overall pattern was evolutionary differentiation punctuated by occasional hybridization and cultural contact between long-separated groups.

    Weckler was not the first to propose that Neanderthal and modern lineages had been relatively isolated and later hybridized. The idea was widespread after the description of the Mount Carmel remains by McCown and Keith [3]. McCown and Keith themselves had favored a different explanation -- that the Skhul and Tabun remains represented a transient between a less specialized and more specialized (Neandertal-like) extreme. Others, including Carleton Coon [4] and Theodosius Dobzhansky [5], immediately favored the idea that the Mt. Carmel sample represented a hybrid population.

    Weckler broadened the idea of hybridization into a general theme. He supposed that we might expect recurrent contact during second (Mindel-Riss) interglacial times in Central Asia, and repeated dispersal from India into Southeast Asia throughout the Pleistocene. Thus, hybridization between divergent groups was not a one-time affair but instead was a fundamental aspect of Pleistocene human evolution.

    Interglacial population contact

    This scenario faced an obvious problem: There were essentially no data to test the hypothesis of population contact at any of these earlier times. Only the third interglacial, already treated by other authors, gave the appearance of sufficient information for a test. To illustrate the plausibility of recurrent exchanges, Weckler fleshed out a third interglacial model of population contact in some detail:

    Some of these pre-Neanderthal men wandered inland into Asia north of 40° during a period of warm climate. Part of this population may subsequently have been trapped north of the barrier in the general vicinity of Inner Mongolia or Sinkiang at the onset of the next glacial period. Primitive man caught in this area would have been unable to retreat directly southward because the great mountain mass that lay in that direction became frigid sooner than the lower lands to the north. Having lived where he was for hundreds of generations, primitive man might not have known he could escape the increasingly rigorous climate by moving east several hundred miles before turning south. Howell (1951:409) suggested that some of the physical characteristics of classic Neanderthal man may represent biological adaptation to a glacial climate. Coon stated in a letter to me (1953) that he has long been of that opinion. If this is so, I suggest the evolution occurred, not in Europe during the fourth glaciation, but in eastern Asia during an earlier one (Weckler 1954:1010).

    This is an early exposition of the idea that Neandertals repeatedly invaded the west from a homeland somewhere in central Asia or further east. Weckler discussed the idea that these populations originated in northwestern China, but he had no good examples (as indeed there are still no such examples).

    Weckler's discussion may seem confused because he accepted Zhoukoudian as an eastern "Neanderthaloid" population. His division of humanity can best be aligned along a "paleanthropic/neanthropic" distinction. Today, we might more simply state his biogeographic model as a shifting border between the paleanthropic "Neanderthaloids" and neanthropic "Homo sapiens" along a shifting Movius line somewhere in India or the Middle East, stretching to northwestern China.

    A central Asian source

    Teshik Tash bears much importance to Weckler's ideas, as it did to Movius, Howell, Weidenreich, and many others. To those unfamiliar with the site, an interesting place to start is my interview with Mica Glantz. Teshik-Tash is once again central to our ideas of Neandertal biogeography, with the addition of genetic evidence from the juvenile specimen from the site and others in Central Asia.

    In the early 1950s, Teshik-Tash raised many of the same issues that it does today. Today, of course, Teshik-Tash is far from alone, with several sites in Central Asia bearing evidence of a local Mousterian, physical remains with Neandertal-like mtDNA sequences. There was great uncertainty about the date represented by the Teshik-Tash specimen. Teshik-Tash had a classic "Western" archaeological industry (in this case, Mousterian) and therefore evidenced long-range population contact with Europe. The East Asian fossil record was known to be very different from the west, raising the question of boundaries. Where did the Western sphere of biological influence end, and the Eastern begin?

    Today Denisova Cave, embedding a highly divergent mtDNA clade in an initial Upper Paleolithic assemblage [6], presents the same issues with even greater relief.

    Probably the most common interpretation of the Central Asian "Neandertal" sites is that they represent an eastward migration from the Neandertals' center of evolution in Europe. But the opposite hypothesis is an obvious alternative: that the center of Neandertal evolution was somewhere in Central Asia, and that they invaded Europe from outside. Some may see parallels for a Neandertal invasion of Europe from outside, by looking both earlier in evolution (the first Europeans obviously came from somewhere) and later (the Upper Paleolithic, the Neolithic).

    Why posit Central Asia in particular as a source area, above and beyond the general idea of invasion? I thought the idea might have originated with Henry Fairfield Osborn because of his long interest in Central Asia as a center of human evolution. For Osborn, Central Asia was a source of humanity, but his "Dawn Man" idea supposed that the modern human form had long resided in Central Asia, with more primitive humans at the periphery. The idea that a Neandertal center of evolution existed in Asia is quite different from Osborn's idea, which was itself a sketch supported by little evidence. I'll have more on Osborn later.

    Weckler presented his idea to address a classic problem: To many paleoanthropologists, early Neandertals appeared to be more like later human than were the later, "classic" Neandertals. Howell [7] summed up this observation as follows:

    Many features of early Neanderthal morphology, both cranial and postcranial, are incipiently classic Neanderthal. However, the general morphological pattern of these early Neanderthal peoples bore a close resemblance to that of anatomically modern man, a fact which indicates again the special character of classic Neanderthal morphology (Howell 1957:332-333).

    The early Neandertals were those from the third interglacial, which during the 1950's would have included those from Krapina, Ehringsdorf, and Saccopastore. Howell's description highlights the most common hypothesis: classic Neanderthals had evolved toward greater and greater specialization over time.

    Weckler took a different approach: for him, the fourth glaciation Neandertals descended from already-specialized ancestors, who had existed in Central Asia:

    The Asiatic migrants, probably already mixed with Homo sapiens in central Asia in the Middle East, pushed on to central Europe during the third interglacial. They may have moved northwestward from Palestine or directly westward along the north face of the barrier. In the zone of contact in western Asia and eastern Europe further miscegenation and cultural exchange probably occurred. Then, when the climate deteriorated with the onset of the fourth glaciation, the bulk of the Homo sapiens population retreated south as was its wont. This left Europe open to further Neanderthal invasion and set the stage for the modern misconception that classic Neanderthals evolved rapidly (and in a curiously regressive fashion) in western Europe during Würm I. Probably all that actually happened was that additional Neanderthals of more classic type, adjusted by previous experience to life in a cold climate, kept pushing in behind the advance guard and, by weight of numbers, blotted out the neanthropic traits the earlier migrants had acquired along the way.

    Weckler proposed this scenario not long after F. Clark Howell's 1952 paper [8], in which Howell had proposed that climate isolated Neandertals within Europe during the last glaciation, leading to their increasing specialization. According to Weckler, the glaciations had not isolated Europe so much as they had wiped clean the evolutionary slate within Europe. After the last interglacial, migration from a central Asian source brought back a purer strain of Neandertal.

    Out of this welter of fact and interpretation emerge the few concepts necessary to the hypothesis supported in this paper. By the end of third glacial times Neanderthal had probably developed in eastern Asia to something approximating the classic form. His numbers had probably always been small compared to developing Homo sapiens: his range was incomparably smaller, and in part of this range he had no easy retreat from glacial conditions such as Homo sapiens enjoyed. His restricted range (and possibly his sometimes severe habitat) had militated against the racial diversification that characterized the development of Homo sapiens. In spite of his cultural advances his range and numbers were probably sharply reduced during every glacial episode he had to endure. This may be why, although he stood athwart the entrance to the New World, he never expanded his range sufficiently to explore that territory. But as the climate ameliorated after the rigors of the third glaciation, his numbers increased and he did finally expand his range. For reasons not as yet ascertained he looked westward, and the lowlands north of the barrier afforded him a route to Europe.

    Several strains of contemporary thought emerge in Weckler's formulation. Neandertals were always on the edge of extinction, being repeatedly driven to low numbers by deteriorating climate. Their tenuous existence did not allow them to disperse more broadly.

    That old Neandertal magic

    Where Weckler differed from the received view is in the way he accentuated the Neandertal positives. He wrote that the diversification of humans and Neandertals presented an opportunity to the evolution of our species. From their central Asian source, the Neandertals had acquired innovations necessary for existence in the cold north. Human colonization of these regions might be impossible without the adoption of Neandertal cultural and behavioral innovations:

    The Homo sapiens groups that retreated south from Europe and perhaps from central Asia [during the glaciation] had been touched by Neanderthal magic. They may have acquired some Neanderthal physical traits, but, more important, they had achieved a new cultural outlook. They had perhaps learned the use of fire, clothing and specialized hunting techniques, and possibly of cave dwelling -- accomplishments that freed man from dependence on a mild climate and from a grubbing existence (emphasis added).

    I find myself reading this on two levels. On the concrete, empirical side, Weckler would soon be proven wrong. Neandertals didn't invent fire; that was much older and more broadly shared by Middle and Late Pleistocene humans. They may have had better clothes for cold weather than contemporaries who lived further south, but the innovations of woven cloth, sewn garments, and shoes happened later. They certainly had specialized hunting techniques, but these were linked to a particular kind of social organization and technology. Later developments in both would have required new hunting (and gathering) methods. None of them lived in caves very often; their experience must have been fairly "grubbing" in either event.

    But on the abstract, Weckler presents a scenario where Neandertals had something of value, cultural or physical, without which later humans would have been as successful. He had already posited biological hybridization; here he suggests a kind of "cultural hybridization" as well.

    The essential idea I am suggesting is that the contact of Homo sapiens groups with "Neanderthal culture" in Asia and in Europe during the third interglacial resulted in an efflorescence of "Homo sapiens cultures" that gave rise to the Upper Paleolithic. There is general agreement, I think, that a sudden enrichment of culture is evident at the beginning of the Upper Paleolithic in Europe and that these richer and more varied cultures seem to have originated, for the most part, outside of Europe. Movius, discussing the European Upper Paleolithic (1953:171ff.), follows M. Denis Peyrony, Dorothy Garrod, and others in suggesting that different European cultures of that time may have originated in Palestine, Iran, the plains of southern Russia, and possibly Africa. All but the latter are areas where indigenous Homo sapiens was probably directly stimulated during the third interglacial by invading Neanderthal man (Weckler 1954:1016).

    So why has this idea been largely forgotten? The failure of the particulars was almost complete:

    Leakey claimed in the 1930's that Lower Aurignacian techniques of stone chipping were older in Africa than in Europe (1931:237-39; 1936:54-60, 161). Movius seems ready to dismiss Africa as a source of European Aurignacian (1953:171), but he doesn't dispose of Africa's claim to temporal priority. The sudden new competence Leakey claims for African Aurignacian cultures early in the fourth glaciation (1936:161) may have been the consequence of contact with Neanderthal. The stimulation may have come secondhand from Homo sapiens wanderers returning from Europe or may have resulted directly via diffusion or migration from the Middle East.

    He was overreaching here. He didn't overestimate the cultural sophistication of Neandertals, although he did accentuate behaviors, like fire, that would turn out to be less special than he assumed -- older than Neandertals and more broadly shared. More critically, Weckler rested his argument on the absence of evidence for cultural sophistication in the African contemporaries of the Neandertals. But Louis Leakey's earlier claims about an "African Aurignacian" also overreached, supported by a mistaken chronology. A better understanding of the Late Pleistocene African cultural sequence would emerge only later.

    When Homo sapiens had thoroughly assimilated and improved on the ideas he got from Neanderthal, he took advantage of the first interstadial of the Würm glaciation to launch forth on his initial conquest of the world. He overran Europe and pushed around the barrier into eastern Asia.... One might even hazard the guess that the reason Africa south of the Mediterranean littoral remained so backward during the Upper Paleolithic was because the Homo sapiens groups there had not had the full benefit of Neanderthal stimulation. In the new dynamics of cultural enrichment and sapiens migrations the hinterlands of Africa had become a dead end, far removed from the centers of rapid development.

    I find myself wondering about the nature of "Neanderthal stimulation"....

    This passage is worth examination. Most of the details have changed radically since 1954. We now know that MSA Africans had most of the tricks that Neandertals did, and vice-versa. Many MSA industrial innovations predate Mousterian or Middle Paleolithic occurrences. The complexity within Africa may itself represent a vastness of population history that we now can only guess at.

    Yet the development of Upper Paleolithic cultural complexity still wants some explanation. The biological innovation of "anatomical modernity" is not sufficient to explain the cultural evolution of the Late Pleistocene -- it does not match the pattern of cultural innovation in time or space.

    Bottom line

    I think there was some "Neandertal magic." Middle Pleistocene humans were more isolated than present-day populations, for a longer period of time. Less gene flow made it less likely for adaptive traits to spread beyond the population where they originated. Not impossible, just less likely. So any surge of population contact caused by migration would have been accompanied by a surge of introgression of adaptive genes. The evidence for Neandertal contribution to the later gene pool of non-Africans documents one such surge of population contact, but there may well have been others.

    Where genes are concerned, this is a simple matter of mathematics, discussed more fully by Greg Cochran and I in our 2006 paper [9]. Simply put, Neandertals and modern humans had comparable selection pressures for many aspects of their biology, similar adaptive responses, and the same time to adapt. Adaptive mutations are chance events, governed by demography and time. If the evolving African MSA population got many new adaptive mutations, Neandertals would have gotten nearly as many (possibly constrained by smaller population size). In a few cases, the same variants would occur in both populations by chance, but in most they would be different. These alleles should still be with us, as the extent of Neandertal contribution to our population was great enough to pick up almost all of them.

    But what about Neandertal cultural traits? These were the real focus of Weckler's argument, and here I think the question is very difficult to resolve today. Cultures are ephemeral. As we know from history, if we choose a beginning and end point a few hundred years apart, it can be difficult to show the continuity of cultural information even within a single place.

    With the transition from Mousterian, through Châtelperronian into Aurignacian in France and northern Spain -- a place where we have relatively dense archaeological documentation -- we are nevertheless talking about time gaps of hundreds of years. I'm skeptical that we're in a position to test the hypothesis of cultural exchanges across these time periods.

    We're in a better position to test the hypothesis of stasis. If genetic exchanges happened in the absence of culture change, that would tell us something very relevant to the relation between gene flow and demographic contact. Likewise, persistent stasis of different cultures in adjacent areas tells us something about the absence of information flow. A kind of regional stasis, over thousands of years, seems to have been the norm in MSA and Middle Paleolithic contexts, and it's not a pattern that we are well-placed to understand without a better understanding of the limits on information exchange. Some of those limits may, in these ancient populations, have been biological constraints. So I'm less confident that we will be able to understand the cultural consequences of Neandertal contact.

    References

    1. Weckler JE. The Relationships Between Neanderthal Man and Homo sapiens. American Anthropologist. 1954;56:1003–1025.
    2. Hoijer H. Joseph Edwin Weckler, Jr. 1906-1963. New Series [Internet]. 1964;66:1348–1350. Available from: http://dx.doi.org/10.2307/667992
    3. McCown TD, Keith A. The Stone Age Man of Mount Carmel: The Fossil Human Remains from the Levalloiso-Mousterian. Oxford: Clarendon Press; 1939.
    4. Coon CS. The Races of Europe. New York: MacMillan; 1939.
    5. Dobzhansky T. On species and races of living and fossil man. American Journal of Physical Anthropology. 1944;2:251–265.
    6. Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Paabo S. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature [Internet]. 2010;464:894–897. Available from: http://dx.doi.org/10.1038/nature08976
    7. Howell FC. The evolutionary significance of variation and varieties of "Neanderthal" man. The Quarterly Review of Biology. 1957;32:330–347.
    8. Howell FC. Pleistocene glacial ecology and the evolution of "Classic Neandertal" man. Southwest Journal of Anthropology. 1952;8:377–410.
    9. Hawks J, Cochran G. Dynamics of Adaptive Introgression from Archaic to Modern Humans. PaleoAnthropology. 2006;2006:101–115.
    Tags: 
    Neandertal DNA
    history of anthropology
    hybridization
    extinction
    climate
    introgression
    Neandertals
    migration
    paleoclimate
    Synopsis: 
    A 1954 paper expresses a very modern perspective on climate and Neandertal evolution

  • Mailbag: Zorse pigmentation

    Wed, 2010-09-15 20:59 -- John Hawks

    Re: Horse-zebra hybrids

    I know you saw the picture of the zebra horse in the NYT this morning. Are we SURE that hasn't been photoshopped? I mean, I know it is the NYT, but it makes me thinkk that I don't understand ANYTHING about genetics at all!

    Yeah, apparently this particular one is unique.

    The stripes come from patterning genes that activate the melanin pathway; the pattern gradient inhibits expression of a gene that synthesizes melanin. White spots occur when a different gene is turned off, on the same pathway. So the two combine -- it's like a palomino that has stripes instead of splotches, I guess.

    I have a slide that shows a cattle-bison hybrid with similar spots, like a cow.

    Tags: 
    media
    introgression
    non-primate
    hybridization

  • Mailbag: The Neandertal fraction

    Tue, 2010-09-07 15:22 -- John Hawks

    Re: Neandertal DNA

    I have a question about your "Neandertals Live!" entry written on May 8, 2010.

    When you say that living non-African populations (ancestry) derive
    1-4% of their genomes from Neandertals, does this mean all living
    individuals of non-African descent have some genomic contribution from
    Neandertals? In other words, could one say if you or myself
    specifically have some kind of Neandertal DNA contribution? Or, does
    the 1-4% only refer to certain populations outside of Africa, while
    nothing can be said about individual non-Africans?

    For example, would having Neandertal genes be analogous to certain
    populations, like certain ethnicities, having a particular founder
    mutation on a haplotype, like sickle-cell anemia in people of African
    descent? In other words, some living groups of individuals have them,
    but not all living individuals have them?

    The comparison results from the greater similarity of European (and other non-African) people to the Neandertal sequence, compared to African people. It takes 1-4% genetic contribution to explain this similarity.

    That's an unusual comparison, and it leads to unusual limitations. The number is genome-wide and we don't know (yet) whether some parts of the genome are more consistently Neandertal than others. We also don't know (yet) whether Africans have no Neandertal at all, or just 1-4% less than non-Africans.

    We know nothing at all about individuals (at this moment) although I expect we'll be able to say something about the heterogeneity of Neandertal contribution fairly soon.

    I expect that some genes will have a very common Neandertal-derived haplotype outside of Africa because of selection, and that these will account for a predominant fraction of the admixture. But I can't say we know this yet empirically.

    Tags: 
    Africa
    Europe
    Neandertals
    introgression
    admixture
    Asia
    Neandertal DNA

  • Invasive argument

    Wed, 2010-08-11 10:07 -- John Hawks

    I've been reading a lot about invasive species lately, for reasons which will soon become apparent.

    This morning, Ronald Bailey of Reason magazine has an essay about biological invasions: "Invasion of the invasive species!" Bailey notes that invasive species often increase local biodiversity. He then wonders why this is a bad thing?

    The fear among opponents of "invasive species" is the aggressive outsiders will cause a holocaust among the native plants. That might initially seem reasonable because there are a few species, like kudzu, purple loosestrife, and water hyacinth, that grow with alarming speed wherever they show up. But that doesn't mean other species are in danger. “There is no evidence that even a single long term resident species has been driven to extinction, or even extirpated within a single U.S. state, because of competition from an introduced plant species,” Macalester College biologist Mark Davis notes [PDF]. Yet this spurious threat of extinction persists as one of the chief reasons given for trying to prevent the introduction of exotic species.

    Here's why it's a bad thing: Exponential growth. It starts small, but once it gets going it's very expensive or impossible to slow or stop. Gypsy moths. Emerald ash borers. Fire ants.

    Bailey correctly notes that the effects on birds are much more noticeable than those on plants, but doesn't observe that this is because the population sizes of plants are vastly larger than birds. It's harder to make a plant extinct. With less than a couple hundred years separating us from the initial introduction of most invasive species, it's too early to assess the extinction rate of indigenous species. And it's disingenuous to say that we haven't documented an extinction, when we're spending millions of dollars to prevent them! Plus, he's dead wrong when it comes to islands, where reductions in native flora have rapid impacts on native animal populations.

    For Bailey, it comes down to aesthetics -- people like their nature pure and unadulterated by species from the wrong part of the world:

    Fair enough. But this is not a scientific argument. Sax and New Mexico University biologist James Brown correctly observe that whether the impacts of introduced species “are considered to be positive or negative, good or bad is a subjective value judgment rather than an objective scientific finding. Scientists are no more uniquely qualified to make such ethical decisions than lay people.”

    But his essay isn't about introduced species, it's about invasive species. We can't easily predict which introduced animals will become the next fire ants or zebra mussels. Who would have predicted that lionfish would become a huge problem in the Caribbean? It doesn't take an ethicist to figure out that it's hard to keep something manageable when you can't predict its growth rate!

    Sure, some people like the Everglades better with all those pythons. A few yokels was all it took to put them there.

    Tags: 
    introgression
    ecology
    invasive

  • Libidinous Neandertal men and the women who loved them

    Mon, 2010-05-10 21:54 -- John Hawks

    I keep seeing people, who really ought to know better, saying that the new Neandertal genome results show that the gene flow must have been Neandertal men mating with modern human women, and not the other way around.

    You see, they're fixated on the idea that the mtDNA showed no signs that the Neandertal clade survived into the present-day population. That result really convinced some people that interbreeding was impossible. They're flummoxed that some of the rest of the genome has significant signs of intermixture. It's like their world is spinning out of control. I'm not naming any names, but if you've followed much of the press around the Neandertal genome, you've probably seen this suggestion.

    I don't know why it hasn't occurred to them that the Neandertal mtDNA type was probably lost because of natural selection.

    To avoid raising the awful specter of Darwin, they've been talking about weird mating restrictions. Well, I suppose that if you really have to find a way to get Neandertal nuclear genes into us, without bringing mtDNA along, a total lack of Neandertal women contributing genes is formally one way to get that.

    I'd just like to see these people explain how exactly we managed not to get any Neandertal Y chromosomes, either.

    Is it safe to talk about selection, now?

    UPDATE (2010-05-11): A reader writes:

    With regard to your latest blog post on lack of neanderthal mitochondrial and Y chromosome DNA in humans: yes, it's possible natural selection had a part. However, given that only a small proportion of our ancestors seem to have been neanderthals at the appropriate time, it strikes me that this is a case where drift could be the correct explanation - despite the fact that I'm usually not a big fan of drift as an explanation.

    Much depends on the size of the ancestral population and the pace of population growth in the generations surrounding the pickup of Neandertal genes. Drift is less likely to eliminate alleles in a growing population, but it depends how many copies there were to begin with. The key questions -- where and when the population was growing -- are unlikely to be the same as assumed by the modeling that showed drift couldn't have eliminated the Neandertal mtDNA, as most assumed the location of contact would be Europe and the time would be late.

    There were other deficiencies with the modeling, also. Here we've been working on a source-sink model as a possible demographic scenario for Pleistocene humans; that kind of metapopulation dynamic might easily explain allele losses without selection, and becomes more and more credible as we learn the variance of contribution of Neandertal-like alleles across the genome. It's a different world this week than last week.

    These are all mathematically tricky answers, clever, but academic unless we have good matches to genome-wide variation. Meanwhile a very simple answer, easy to explain to anyone, lies fallow. Exceedingly curious.

    I'd be happy to be proven wrong about the Y chromosome, by the way -- we don't really know that Neandertals didn't have a human-like type, although we do now that today's human population has an exceedingly recent coalescent time. Could be bad estimates of mutation rate. Maybe we'll have more surprises in store.

    Tags: 
    Neandertal DNA
    introgression
    natural selection
    gene flow
    mtDNA

  • African population structure and Neandertal population mixture

    Fri, 2010-05-07 23:09 -- John Hawks

    Green and colleagues, in their paper describing the Neandertal genome sequence, concluded that some genetic mixture between Neandertals and the contemporary African population must explain the genetic diversity of today's non-African populations.

    But they briefly discussed one other possibility -- that African population structure by itself might lend the appearance of Neandertal admixture. I've now seen a number of people raising this possibility in press accounts of the findings.

    I find it surprising that this hypothesis made it into the final paper, because it's so easy to refute.

    The hypothesis is that Neandertals diverged from an already-regionally-diversified African population some 300,000 years ago, with no subsequent interbreeding.

    If that's true then there should be no Neandertal genes that coalesce with human genes more recently than 300,000 years ago -- a bit over 4.6 percent the time of the average coalescence of human and chimpanzee genes.

    I'll assume throughout a human-chimpanzee genetic coalescence of 6.5 million years, the same number used in the paper by Green and colleagues, though the true number may vary from this estimate to some extent. We know which differences between humans and chimpanzees are human-derived, by comparison with other primate genomes. So we can refer to the proportion of the human-derived substitutions, compared to chimpanzees, that are either present or absent in Neandertals. This gives a way of estimating the genetic similarity of Neandertals with recent humans, without having to count the many false-positive changes in the Neandertal sequence.

    Figure 3 in the paper reports the genetic difference between 100-kb windows in the Neandertal genome versus the human reference sequence, as a proportion of the human-derived substitution number within each window. The Neandertal sequences have a high number of cases with complete sequence identity with the human reference, considering only those human-chimpanzee SNPs. Indeed, in the low percentage categories, the Neandertals are closer to the human reference sequence than the San individual.

    This category of high-gene-identity windows is presumably due to the fact that the (European ancestry) human reference genome includes Neandertal-derived genes. In other words, it's another consequence of population mixture.

    But let's examine the alternative hypothesis, that humans within Africa already had established substantial regional population structure by 300,000 years ago, when the Neandertals diverged from northeast Africans. In that scenario, the Neandertal genes should never have diverged from any recent non-Africans less than 300,000 years ago. Again, this is approximately 4.6 percent of the average coalescence time of human and chimpanzee genes.

    Now, look at figure 3:

    Figure 3 from Green et al. 2010

    The modal difference between the human reference and the Neandertals is around 12 percent of the human-chimpanzee genetic difference, which would correspond to a coalescence time of human and Neandertal genes around 780,000 years. Not much lower than the estimate in the paper of 825,000 years -- this difference is due to the shape of the distribution, as the mode is smaller than the mean.

    Now, what we care about is those very low categories, where the human-Neandertal difference is less than 2 percent of the total time to the human-chimpanzee common ancestor. How likely is a 100-kb interval to have this pattern, if the true coalescence time must be more than 300,000 years ago?

    Well, this isn't a formal analysis, but the back-of-the-envelope answer is obvious -- it's very unlikely. The average 100-kb interval has more than 500 substitutions on the human lineage. In a given 300,000-year period, there should be more than 22.5 of them. The probability of observing fewer than 10 in such an interval is 0.0026. The probability of observing zero is 1.7 times 10-10.

    So seeing the results in figure 3 just aren't credible under the hypothesis of ancient African population divergence and no Neandertal-human mixture after 300,000 years. Not unless there are some problems hiding in the data that would interfere with these comparisons. Those bins with little difference between the Neandertals and the human reference genome really have to be explained by coalescent times much younger than 300,000 years -- and those can only be there by population mixture.

    Tags: 
    introgression
    population structure
    Africa
    Neandertal DNA

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Neandertals

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