The divisibility of human ancestry

By Razib Khan | August 25, 2011 6:05 pm

The class human or H. sapiens refers to a set of individuals. On the grand scale it’s really not all that clear and distinct. When do “archaic” humans become “modern” humans? Taking into account human variation, what is a “human universal”? A set of organisms are given a name which denotes the reality that they may share common ancestry, and interact behaviorally, and are potential mates. But many of these phenomenon are fuzzy on the margins. Many of the same issues which emerge in the “species concept” debates are rather general up and down the scales of natural complexity. A similar problem crops up when we conflate the history of genes with the history of populations. Such a conflation has value and utility to a first approximation. The story of mitochondrial Eve was actually the history of one particular locus, the mitochondrial genome. But it did tell us quite a bit about the history of the human species, even if in hindsight it looks as if some scientists overinterpreted those findings. One of the major issues I’ve noticed over the past year, with the heightened likelihood of archaic admixture in the modern human genome, is that people regularly get confused by the difference between total genome ancestry, and the evolutionary history of one particular gene.

Consider the possibility that a substantial proportion of the genetic variants at the dystrophin locus amongst Eurasicans (non-Africans) derive from Neanderthals. As I have observed one of my siblings carries only the Neanderthal variant (males have only one copy as this gene is on the X chromosome). Does this mean he is 100% Neanderthal? Obviously not. The patterns at one gene tell you the history of that one gene. Since the patterns across genes are correlated because of shared evolutionary history (ergo, the existence of geographical racial clusters) one gene can tell you more than just its own history because you are aware of the correlations. But you can’t take this too far. My sibling is less than 5% Neanderthal across his whole genome. He just happens to be “100% Neanderthal” at that gene. There isn’t a great contradiction here. His genome is not a Platonic ideal or a pure category of human vs. non-human.

I bring this up because a few months ago I relayed the findings at a conference as to the evidence of lots of introgression into the human genome from archaic hominins on immune related loci. The paper reporting those findings is now out in Science, The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans:

Whole-genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic HLA class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.

Introgression implies more than just ancestry. These results indicate that Denisovan ancestry at particular immunologically relevant loci is rather high amongst East Asian groups which have no discernible Denisovan ancestry across the total genome. Presumably that’s an artifact of the limits of statistical power in detecting very low levels of admixture. But out of tens of thousand of genes it is not unimaginable that there are some few gene copies from exotic sources which turn out to be adaptive, and so favored over “native” alleles (cultural analogs come to mind; the Roman language remains, but the Roman religion has been replaced by a Jewish derived sect). The paper has little new beyond the conference talk. Note this result:

From the combined frequencies of these six alleles, we estimate the putative archaic HLA-A ancestry to be >50% in Europe, >70% in Asia, and >95% in parts of PNG (Fig. 4, C and D). These estimates for HLA class I are much higher than the genome-wide estimates of introgression….

More precisely, the introgression estimates are around an order of magnitude greater than admixture. Intriguingly the authors note that though most Africans exhibit some evidence of introgression from Eurasian populations, Khoisan and Pygmies do not. This seems to point to the possibility that the generic class “African” may hide a lot of interesting population structure and history. It is clear that peoples from the Horn of Africa seem to have been recently influenced by Eurasian groups, but it may be that West and East Africans more generally have been touched by deep-time back-migrations. Though I’ve been skeptical of attempts to portray Khoisan and Pygmies as “ur-humans,” these results suggest that that characterization may be closer to the mark than I had argued earlier.


Comments (9)

  1. So Africans have introgression from Denisovans but not Neanderthals? Curious, since hybridization with Neanderthals is supposed to have taken place among the earliest of out-of-africans, including the ancestors of those who would go on to hybridize with Denisovans. That would suggest differential selection.

  2. kirk

    I tend to think of these processes as moves in design space across a fitness landscape. If my offspring from my Neanderthal mate has only the immunity improvement gene expressed then the totality of effects in the phenotype (good and not so good) from that collection of genes plus epigenetic influence either moves me from a fit phenotype (and offspring) on the fitness landscape to a more or less equal or slightly improved spot on the fitness landscape. But this is a moving target as my sister is sleeping with another Neanderthal and my nieces and nephews may turn out better or worse on the fitness landscape. These initial moves in design space have to propagate into significant populations. Which means they cannot die in floods or wild fires or be eaten by wild beasts. What happens in Vegas stays in Vegas. Reverse engineering moves in design space across fitness landscapes gives me ‘what fitness landscapes want’ or the selfish fitness landscape.

  3. dave chamberlin

    I appreciate Razib’s carefully measured reporting on what we know about our distant past. Human evolution theorists have long had the problem of 1)portraying themselves as experts when they are not and 2)loss of objectivity by personally attatching themselves to a particular theory. Very slowly a more accurate and complex picture is emerging. I can’t help but wonder if research on the adaptive introgression of our immune system is encouraged but that research on adaptive introgression of genes influencing brain function is not just discouraged but a potential career killer. Nothing could be more interesting to me than what genetic imput from archaics gave us mental advantages but it just seems too touchy an area for researchers dependent on grant funds or risk of losing tenure track.

  4. Great post Razib. I particularly liked how you explained the distinction between admixture and introgression in the las paragraph. I wonder if these HLA haplotypes were locally adapted to particular prevalent diseases in the archaic populations and therefore were rapidly selected for, possibly facilitating subsequent colonisation of the expanding AMH.

  5. miko


    no need to invoke liberal academic conspiracies; it’s because you’d have to be a total idiot to pick a trait (let alone a highly complex and poorly understood one) and then go looking for evidence that archaic admixture has influenced it. instead, you find loci, and this guides you to affected traits. we understand the genetics of the immune system incredibly well and the genetics of the kinds of cognitive traits you’re interested in not at all. there is a major discovery bias toward traits with well-understood genetics.

  6. Sandgroper

    Dave, I don’t want to start again, but you said “loss of objectivity by personally attatching themselves to a particular theory”, then you said “Nothing could be more interesting to me than what genetic imput from archaics gave us mental advantages”.

    I don’t know what it is that is exciting you about this.

  7. dave chamberlin

    Miko and Sandgroper

    I don’t fancy myself quite an idiot but I do think that I am quite ignorant as compared to Miko on practical matters regarding present day research in Genetics. In short I defer to your greater expertise on these matters Miko. My perspective is more a childish sense of wonder rather than the preferred disciplined scientific approach on this blog, I think it quite marvelous to attempt a distant perspective on our brief moment in time. Better brains got us to where we are and better brains will in all likelyhood get us to where we are going. I have no illusions on how complex life is and specifically how complex and how little we now know about how the human brain works and how genetics makes each of us so variable in what we refer to as intellegence. It will be a generation at least until what I believe to be the ultimate Rosetta stone is decifered, how our DNA makes us human in our thinking. Bruce Lahn went looking for genes important in fetus and infant brain development that have undergone recent selective sweeps, meaning they have some positive effect allowing them to spread faster than random chance in the human population. He found one which much like the HLA haplotypes has only spread regionally. He was accused of fostering racism and given a ton of shit. He choose to leave his research position in the United States and return to his homeland China shortly thereafter. It is there that billions will be spent in the decades to come in this sensitive area of reseach, not the United States. I am not insinuating a liberal acedemic conspiracy because I long ago realized to never blame on a conspiracy what could just as easily be attributed to human stupidity. Steve Hsu at his blog has discussed the particulars of a very ambitious and long term project in China that will attempt to find differences between people of average and genius IQ. I dream that we will someday find out what complex genetic combinations gave us our modern day intellegence and what complex combinations make us so variable today and one area of research will assist and be highly related to the other. I dream that the result of this knowledge will launch a human revolution as transformative as the industrial revolution. Time will tell if I am an idiot or a visionary or just an everyday mix of both.

  8. Sandgroper

    I don’t think anyone was calling you an idiot. What I don’t get is why you seem convinced that Neanderthal admixure gave cognitive advantages when, as far as I can see, there is no evidence that is the case. I’m not saying that it is not the case, but where is the evidence for it? It is loss of objectivity that I am concerned about.

  9. dave chamberlin

    I think it far more likely that the influx of 1% to 4% of our 20,000 genes from Neanderthals caused a hybridization that resulted in our modern intellegence. The alternative theory presented before we knew of intermixture between out of Africa moderns and Neanderthals was some transformative mutation. I could be wrong, not much is known, to me it is a matter of probabilities from what we know now. I am not convinced of anything because the evidence is so minimal.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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