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7531-1477645031Eurogenes points me to this interesting conference with a book of abstracts, Human Dispersals in the Late Pleistocene – Interdisciplinary Approaches Towards Understanding the Worldwide Expansion of Homo sapiens. Below are those of interest to me….

Philipp Gunz

Max Planck Institute for Evolutionary Anthropology
Leipzig, Germany

Evolution and development of the modern human
face and brain

A number of fossils from North, South, and East Africa document the early stages of our species, and fossils from the Levant document the presumed first wave of migration out of Africa. The exact place and time of our species’ emergence remain obscure as large gaps in the fossil record and the chronological age of many key specimens make it difficult interpreting the evolutionary processes and population dynamics shaping the cranial diversity of modern humans. Here we use 3D geometric morphometrics based on landmarks and semilandmarks to compare facial and endocranial shape in a worldwide sample of recent and fossil humans from Africa, Europe, and Asia.

Our data support a complex evolutionary history of our species involving the whole African continent. Regarding facial shape, we find that even the early H. sapiens specimens fall within the shape variation of recent modern humans. Endocranial shape, however, changes considerably within the Homo sapiens lineage.

51t3ZeiK+vL._SY344_BO1,204,203,200_ I think I understand archaic introgression better now. Humans really care about faces. Brains? Not as much. If our species developed its normal range of species-typical faces rather early on than we’d recognize each other as conspecifics, despite widespread phenotypic differences (including likely cognitive and behavioral) and genetic divergence. Basically, it’s just like the Trojan War; a face can launch ships, and mediate gene flow.

John Hawks

University of Wisconsin-Madison, USA

African population diversity and its relevance for human dispersals

As modern humans dispersed throughout the world, they encountered and mixed with populations with much greater genetic distinctiveness than any living humans today. This process is now relatively well documented by ancient DNA in Eurasia and Australasia due to the ancient DNA records of Neanderthal and Denisovan samples. Within Africa this process of contact and mixture between genetically differentiated populations also took place, evidenced by the evidence of population mixture from genomes of some African populations today. The process began earlier, well before 100,000 years ago, and may have extended over a longer period of time. The evidence suggests that modern humans originated and began their dispersals within an African continental context equally or more genetically structured than Eurasia. However the fossil record of this population is very sparse, and it is not evident how archaeological distributions may relate to biological populations. Here I discuss the implications of this population structure for human dispersal and adaptability. T he modern human phenotype originated as one well adapted for dispersal within a long-existing network of successful populations of potential competitors.

Basically it strikes me that John is developing and extending the neo-multiregionalist framework that he was operating within in the early 2000s. Also, African substructure is a thing. A major thing.

Finally, but not least:

Stephan Schiffels

Max Planck Institute for the Science of

Human History, Jena, Germany

Analysing Australian genomes to learn about early modern human dispersal out of Africa

When and how modern humans left the African continent is still a debated question. Recently, three projects have analysed new genetic data from modern populations in Papua New Guinea and Australia, which has provided new insights on this topic. I will present analyses from one of these publications (Malaspinas et al. 2016), and compare results with findings from the two other projects (Mallick et al. 2016, Pagani et al. 2016). Here, we used MSMC2, a novel computational framework to analyse the distribution of times to the most recent common ancestor along multiple sequences. We find that all non-African populations that we analysed, including Australians, experienced a very similar population bottleneck in the past, consistent with only one out-of-Africa migration for all extant non-African populations. At the same time, we find evidence that some African populations are more distantly related to Australians than to Eurasian populations, and we show that this result is robust to haplotype phasing errors and archaic introgression. We interpret our result as evidence for gene flow between some Africans and Eurasians after the initial split, which is also consistent with results from other population genetic methods. Our analysis suggests that in order to understand human dispersal out of Africa, we need to better understand ancient population substructure within Africa, which is an important direction for future research.

Again, ancient African substructure. No coincidence. Talk to the cutting edge people in the field, and this is the fabric of reality that the knife’s edge is going to slice in the near future. Second, I do believe it is likely that there was non-trivial gene flow between Sub-Saharan Africa and Western Eurasia over the past 50,000 years. Some of this is masked perhaps by low levels, but, just as likely in mind, ancient African structure which has been erased due to population turnover.

• Category: Science • Tags: Genetics, Human Evolution 
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220px-Pointes_de_chatelperron A new paper in PNAS, Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne, weighs in the question of whether the Châtelperronian culture were Neandertals, with an answer in the affirmative in this case:

The displacement of Neandertals by anatomically modern humans (AMHs) 50,000–40,000 y ago in Europe has considerable biological and behavioral implications. The Châtelperronian at the Grotte du Renne (France) takes a central role in models explaining the transition, but the association of hominin fossils at this site with the Châtelperronian is debated. Here we identify additional hominin specimens at the site through proteomic zooarchaeology by mass spectrometry screening and obtain molecular (ancient DNA, ancient proteins) and chronometric data to demonstrate that these represent Neandertals that date to the Châtelperronian. The identification of an amino acid sequence specific to a clade within the genus Homo demonstrates the potential of palaeoproteomic analysis in the study of hominin taxonomy in the Late Pleistocene and warrants further exploration.

The details about stratigraphy are beyond me. But the protein and mtDNA evidence is pretty conclusive in my opinion that there are Neandertal individuals in this assemblage. Therefore, assuming their stratigraphy is correct, what you see in the Châtelperronian may be a cultural influence upon Neandertals by anatomically modern humans who were pushing into Europe at this time.

51r8Ph-vcaL._SY344_BO1,204,203,200_ But cultural influence may not be the only dynamic at work. In The 10,000 Year Explosion: How Civilization Accelerated Human Evolution Greg Cochran hypothesized that Châtelperronian culture may have been a vector for Neandertal genes coming into modern human populations. And now we know that this isn’t always one directional. That is, just as modern humans absorbed genes from “archaic” populations, so archaic groups absorbed ancestry from modern populations (or at least humans closer to the main stem of modern humanity).

51dw0Uce+XL._SX330_BO1,204,203,200_ In The Third Chimpanzee Jared Diamond posited that the Châtelperronian Neandertals were analogous to native peoples in the New World such as the Cherokee, who adopted many aspects of European settler culture in their attempt to resist cultural absorption and marginalization. But one dynamic we need to remember about these tribes is that they also had a lot of European ancestry, in part because of the rapidly unbalanced population sizes. It seems entirely likely, as some have posited, that the last “Neandertal” populations were also substantially admixed. Therefore, it is not entirely surprising that they would also tend to exhibit cultural features more commonly found among modern humans.

My prediction is that when whole genomes of Châtelperronian Neandertals are available it is highly likely that they often show evidence of modern human ancestry.

Note: Diamond’s The Third Chimpanzee is in my opinion a very underrated work. It is a bit dated today, but I still think it is quite worth reading.

• Category: Science • Tags: Evolution, Genomics, Human Evolution 
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SHUpdate Ignore stuff on mutation rate. Confused mutation rate per year with per generation. Moral of story: read more closely! End update

The genetic data from the Sima de los Huesos (SH) hominins has finally been published in Nature. Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins:

A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago…While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals…Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.

I don’t want to denigrate mtDNA, but the whole field of phylogeography and inference of evolutionary relationships in non-human organisms has been confused by the fact that many scientists drew a straight-line between the genealogy of a single locus, mtDNA, and the genealogy of a whole species. In light of results from molecular ecology, which long relied on mtDNA, but is finally moving toward genome-wide marker sets because of new technologies, I’m absolutely not shocked that mtDNA is not particularly predictive of whole genome relatedness. Recall that the Denisovan hominin had an mtDNA lineage which was more distant from Neanderthals than the whole genome turned out to be.

More importantly for this paper is that they find that whole genome inferences suggest that the SH hominins are genetically closer to Neanderthals than they were to Denisovans. I’ll skip over their quality control of the ancient samples…the group that published this paper is the best in the business, and it’s broadly persuasive to me…though I don’t know much about this topic, so you shouldn’t put much weight on my opinion. Because of the small amount of data retrieved they used a rather simple method to establish relatedness: shared derived mutations. Basically these are unique mutations which distinguish particular hominin lineages from each other and the outgroup population (other primates).

The above figure shows that the the SH hominin samples share much more with Neanderthals than with Denisovans, and more with Denisovans than with modern humans. From that one might reasonably infer then that:

1) The ancestry of modern humans diverged before the SH-Neanderthal-Denisovan clade.

2) But Denisovans diverged rather quickly from the SH-Neanderthal clade.

3) Since the SH hominin site seems to date to ~400,000 years before the present, and is found in part of the traditional range of Neanderthals, and these individuals share morphological characteristics with this group, the SH hominins may be the ancestral population, or related to the ancestral population, of Neanderthals.

How robust is this date? I don’t know enough geology or paleontology to judge, so I won’t follow the citations. But a lot of the discussion and novelty of these results seems to hinge on this date. From the paper:

This age is compatible with the population split time of 381,000–473,000 years ago estimated for Neanderthals and Denisovans on the basis of their nuclear genome sequences and using the human mutation rate of 0.5 × 10−9 per base pair per year…This mutation rate also suggests that the population split between archaic and modern humans occurred between 550,000 and 765,000 years ago.

A more conventional mutation rate I’ve seen is closer to 1 to 2 × 10−8, or two to four times faster than the one above. But the mutation rate literature is rather confusing for me, and does not totally align well together, possibly due to variation in rate over time.

The picture above is often derived from a model where we fit the diversification of the human lineage to a tree. But within the paper they suggest Neanderthal mtDNA might have been African, and that there may have been an earlier migration out of Africa before the one that occurred ~50-100,000 years ago. I don’t see a priori why this couldn’t be so, but I’m also not clear how we’re going to get a good grasp of the details of the dynamics at play.

Perhaps the dominance of the African “Out of Africa” lineage over the last 100,000 years is an aberration. It may be that much of human history was characterized by the sorts of meta-population dynamics described by classical multi-regionalists. The possibility that Neanderthal-Denisovan divergence might be as old as ~450,000 years before the present suggests to me that the massive replacement and assimilation we saw ~50-100,000 years ago was somehow atypical in terms of how it disrupted deep regional population structure….

• Category: Science • Tags: Human Evolution 
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According to a new paper in Nature, Ancient gene flow from early modern humans into Eastern Neanderthals, a basal population of anatomically modern humans mixed with eastern Neanderthal populations on the order of ~100,000 years ago. The figure above is from the paper, and shows (on the left) the proportions and direction of gene flow across the phylogenetic tree, and (on the right) the dates of divergences and effective population sizes of the various groups. In The New York Times Carl Zimmer has a write-up, Ancient Humans May Have Left a Genetic Mark on Neanderthals (also, see Ewen Callaway in Nature, Evidence mounts for interbreeding bonanza in ancient human species). It’s useful to read, because he reports that some of the researchers assumed their results were in error, so they double-checked, and, other prominent researchers believe that the results are broadly credible. This doesn’t mean the results are correct…though the team that came out with this has people I trust to attend to details, and the results are not implausible on a priori grounds.

51t3ZeiK+vL._SX331_BO1,204,203,200_ Where does this lead us? As observed on Twitter there are some curious results in this paper in terms of the phylogenetic relationships and demographic history of human populations. The modern human lineage which contributed to the Altai individual seems to have done so ~100,000 years ago. This is 40,000 to 50,000 years before the “Out of Africa” event which we know of, and which seems to have resulted in the patterns of human genetic variation outside of Africa, excepting archaic admixture, that we see today. As noted in the paper there have been recent finds in locations such as China of very ancient pre-”Out of Africa” modern human remains, and there has always been the Skhul and Qafzeh hominids in the Near East. So that’s not too much of a problem necessarily. But, if you look closely at the phylogenetic tree above San diverge from other modern lineages ~200,000 years ago, well before the admixture event, but the modern human ancestry in the Altai Neanderthal looks equally related to all modern humans. That seems peculiar, since in the 100,000 intervening years there should have been significant structure to sample. There are a variety of ways to “resolve” this…though as one of the authors stated, there are many reasons why the date of the divergence of the various groups and admixture differ so much (e.g., archaic admixture into the San might push back their divergence from other groups). I need to think about this more and read the supplements. The picture in the details is getting cloudier, not clearer….

But the overall result does clarify and highlight some big picture inferences we can make in generating a framework toward understanding new results. Mait Metspalu’s group is going to publish a paper on low levels of pre-”Out of Africa” modern admixture in Sahul populations (that is, a earlier movement of modern people than the canonical one), and I now judge that their result is a true positive to a higher degree than earlier. These Altai Neanderthals likely did not contribute to modern human Neanderthal ancestry, as the Neanderthal ancestry in modern humans is closer to that of European Neanderthals (who did not have modern human ancestry like the Altai individual). Follow that?

The upshot is that these results should change our prior expectations about the nature of ancient human population structure. Yes, it was complicated, but there’s a pattern. The genetic patterns indicate that there was selection in the genome against the introgressed variants, so Neanderthals and modern humans exhibited hybrid breakdown. In light of no such genomic evidence for admixture of Eurasian ancestry into KhoeSan (I’ve asked, people have looked), that suggests we know that for hominins hybrid incompabilities seem to arise on the scale of between 200,000 and 600,000 years. It also seems that due meta-population dynamics lineage extinctions were very common in hominins. The genetic relatedness of Neanderthals across human swaths of territory indicate that they were subject to this dynamic, where there were massive lineage pruning events over the 600,000 years that this group was a distinct population. With modern humans, we now know that first settlers do not always leave a genetic impact later on because of extinction events. With these facts under our belt it is less surprising if there were “false dawns” of the “triumph of humanity.”

mmXlVoUaP2In-yXZPl_WuZg What these results do warrant though is the final expiration of a particular narrative of the explosion of humanity ~50,000 years ago due to singular biological changes that cascaded themselves into a cultural explosion, where the hominin-made-man swept all before them. Probably the best illustration of this thesis can be found in Richard Klein’s 2002 book, The Dawn of Human Culture. In it he proposes that 50,000 years ago there was a single mutation which resulted in a pleiotropic cascade, and allowed for the emergence of full elaborated language and ergo the package of features which we associate with behavioral modernity. This model was presaged in the earlier decade with popularizations of “mitochondrial Eve” which implied that all humans were descended from a very small tribe resident in East Africa on the order of ~100,000 years ago. (the date varied as a function of the vicissitudes of mutational rate estimates)

Here’s what we know now that changes this. First, there are populations within Africa, in particular the the San of the far south, who diverged much earlier than 50,000 years ago. The most recent genomic estimates are suggesting divergence dates as early as ~200,000 years before the present. Second, the effective population size of humans outside of Africa is incredibly small, suggesting expansion from a very small founding population, but one should be cautious about generalizing to groups within Africa. That is, the blitzkrieg sweep model of modern human expansion does not hold to within Africa, and there is both archaeological and genomic inference to indicate the persistence of highly diverged hominin lineages in that continent until relatively recently. And, these lineages may have admixed with modern humans just as they have outside of Africa.

Finally, the emergence of H. sapiens sapiens supremacy seems to have been a process, not a singular event which emerged de novo like a supernovae in the hominin firmament. The Omo remains in Ethiopia were anatomically modern humans. The people who gave rise to Omo lived ~200,000 years ago. The encephalization of the human lineage increased gradually up until around ~200,000 years ago, and Neanderthals were famously the most encephalized of all. Therefore, some form of modern humans were present within Africa for 150,000 years while other lineages were dominant elsewhere. Remains from places like China suggest though that offshoots of African humanity did push into the rest of the world…but they may not have left much of a genetic trace. This may have been part of movements due to climate change during the Pleistocene, or one of the natural migrations which a consequence of Malthusian pressures and inter-deme competition which afflicted humans. But they clearly did not conquer all before them. Why? We don’t know. And we don’t know why the situation was different 50,000 years ago. As a null hypothesis one might entertain the possibility that it was random. That periodically turnovers occur, and it just so happened that an African lineage lucked out in a massive extinction event. But that’s hard to credit when you consider that these modern humans crossed into Sahul and Siberia after sweeping aside other groups, and then eventually crossed over into the New World. There was something different about us. Additionally, the modern humans eventually absorbed or extirpated other lineages within Africa too.

A generation ago many people thought they had the answer. That man was born 50,000 years ago on the East African plain, and the gods gave him the world. Only he was endowed with a soul. Today we know that that’s wrong. We just don’t know what’s right.

Addendum: We need to start thinking about Eurasian gene-flow into Africa over the Pleistocene.

• Category: Science • Tags: Human Evolution 
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The_10,000_Year_Explosion_(Cover) Over at Nature Ewan Callaway has a piece up, Neanderthals had outsize effect on human biology. The upshot is that the few percent of archaic admixture in modern humans, who descend from a Neo-African group ~50,000 years ago, may have significance functionally, and been driven by adaptation. This is not surprising. Greg Cochran and Henry Harpending discussed this dynamic in their The 10,000 Year Explosion (speaking of Greg, he is having a fund raiser). Though not entirely analogous, the work of plant evolutionary geneticists also indicates that we might expect this sort of phenomenon, whereby adaptive variants are absorbed from substrate as populations expand (for a somewhat different angle, though related, see How species evolve collectively: implications of gene flow and selection for the spread of advantageous alleles; I doubt it’s a coincidence that a lot of the deep understanding of evolutionary genetics I have comes from people working on plants).

A few years back I groused to Nick Patterson that the initial Neandertal genome paper in 2010 was overly skeptical of the possibility of admixture resulting in adaptive variants entering the modern human genome pool from archaics. Nick’s argument was simply that they hadn’t detected any such variants at that time, so it was a straightforward thing to report. If you listen to what Ed Green and company stated in the media they were very careful how they parsed their statement in regards non-neutral variants. My rejoinder was that on prior grounds it is hard to imagine that out of a few percent of the genome there wasn’t at least a few significant adaptive alleles.

As Callaway reports above that turned out to be right. I think the original research was a bit too conservative by relying only on empirical results when the theory here seems quite strong. Additionally, I would actually take some issue with the title in the Nature piece. Some of the same researchers have found reduced Neanderthal admixture proportions on the X chromosome, suggesting selection against Neanderthal variants in the admixed genome (a phenomenon common during hybridization between diverged lineages), which is predominantly Neo-African. In other words, the few percent might actually be less than what one might have concluded based on a census count and the genealogy a few generations out of the initial admixture event. It doesn’t really make sense to say that Neanderthal’s had an outsized effect when it is likely that their distinctive variants were also purified somewhat from the genome initially. Perhaps one might say that they had an outsized effect after you control for the fact that deleterious variants from Neanderthals were removed from the equation early on. As it is, and I think as implied in the article, we don’t know enough about the number of functional archaic alleles to adduce whether they have more impact or not. Rather, Neanderthals gave us all things under the sun.

• Category: Science • Tags: Human Evolution 
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"Sapiens neanderthal comparison" by hairymuseummatt - <a href=''  title='' ></a> Licensed under CC BY-SA 2.0 via Wikimedia Commons - <a href=" width="590" height="322" />

First Peoples is PBS’ attempts to update the story of human evolution for 2015, particularly informed by the ancient DNA revolution of the past 5 years. It is worth watching, but not without its faults. The first two episodes are online, and I’ve watched them. Kristina Kilgrove at Forbes has a review of the whole series up. Below are some impressions of the first two episodes.

300px-Namibian_Bushmen_GirlsOne immediate problem is that modern actors have to play the “First Peoples” in reenactments. This imposes limitations. The Africa episode begins with Omo 1, one of the first anatomically modern humans in the fossil record. When dramatically depicting his life and death the actors used looked vaguely East African to me. This stands to reason because Omo 1 died in southwest Ethiopia. But this individual died between 100 and 200 thousand years ago! There’s been a lot of population movement, and evolutionary change, between then and now. There’s no reason to assume that modern Africans are a good representation of ancient hominins who were resident within Africa. The Khoisan people of southern Africa, whose ancestry diverged first from the rest of modern humanity 150 to 200 thousand years ago, look notably different from their Bantu speaking neighbors. The Nilotic Luo of Kenya look different from their Bantu speaking Kikuyu neighbors. And so forth.

To be fair, there is a vaguely similar phenotype among some non-African people in relationship African groups. Melanesians and Andaman Islanders come to mind. Remember, these “African-looking” Asian and Oceanian groups are genetically no closer to Africans than a Swede or Native American (Oceanians are actually somewhat further because of more Denisovan admixture). The best modern genetic data point to common descent for non-Africans from one ancestral population, so that their descendants are symmetrically distinct from all Africans without recent Eurasian admixture.

The important point to remember with these phenotypic racial categories is that these groups are only vaguely similar. Even a geneticist like me can tell that Papuan Highlanders look quite distinct from any African group. Phenotypic variation among Sub-Saharan Africans, Oceanians, and Negrito Asian peoples, should tell us that the human populations of African 100 to 200 thousand years ago were probably also somewhat diverse, even if their expected range of variation is not arbitrary (e.g., it is likely that their skin was on the dark side; loci for pigmentation are somewhat functionally constrained around the tropics). But the expectation should not be overwhelming that modern Africans more accurately reflect the ancestral phenotype of tropical adapted modern humans than, say, Bogainville Islanders.*

My nit with this issue is that it feeds into a larger narrative of “ancient people” and “living fossils.” In the Africa episode the narrator states that Pygmies are closer to the earliest anatomically modern humans. This is wrong. All modern human populations are about equal close to the earliest anatomically modern humans. The main qualification here is that likely all of us have different proportions of ancestry form distinct “archaic” lineages. That is, hominin groups which are outside of the main branch that contributed between 90 to 99 percent of our ancestry. It does seem that the ancestors of the Pygmy groups of Central Africa are the second most basal group of humans in comparison to non-Africans (the most basal being Khoisan). But the generations between early humans and modern Pygmies is about the same as that between early humans and Europeans or Asians or Oceanians. Though we aren’t totally sure from what I know, it also seems likely that the earliest modern humans were residents of the open woodland ecology, and not the deep forest. The presence of Pygmy-like groups across tropical forest biomes from Gabon to the Philippines suggests that in fact this is a derived phenotype. An evolutionary change from the ancestral state.

519gldjJoAL._SY344_BO1,204,203,200_ In general First Peoples does a rather good job by the standards of the media not recycling older models which have embedded an implicit “Great Change of Being.” Though I would find some minor fault in their depiction of the phylogenetic relationship of Pygmies and the first humans and humans more generally, their treatment of hybridization was mixed as best, and misleading at worst. In particular, the attitude toward the idea of species was confused and incoherent. The biological species concept (BSC) comes closest to colloquial understandings of what species are, but First Peoples seems to crystallize this framework as if it was an indubitable iron law of nature. With that in mind, rather frequent instances of hybridization between divergent hominin lineages seem more startling, adding dramatic twists to the narrative. The problem I have with this is that most biologists I know view the BSC as just one of many species concepts. It’s not written in stone, but rather, an instrumental device in getting science done. Obviously the biological species concept, predicated on sexual reproduction, is irrelevant for asexual organisms. Additionally, there are wide swaths of the tree of life where hybridization is ubiquitous. In particular, plants. It is in mammals, with our peculiar system of reproduction which involves rather complex mechanisms of gestation, that hybridization barriers are particularly high. But even among mammals there is variation in obstacles to hybridization conditional on placenta type.

With all that in mind it’s pretty unsurprising, with hindsight, that there was gene flow across diverged hominin lineages. First Peoples itself acknowledges this likelihood by referencing research on baboon hybrid zones, and asserting that this phenomenon might be totally par for the course among primates. There’s nothing special about humans biological makeup then that would preclude hybridization.

Not only does hybridization play a role in the emergence of new human traits (one researcher seems to imply that human faces are subject to a liger-like effect), but John Hawks seems to posit a multi-regionalist like model for the origin of modern human within Africa, whereby hybridization between lineages eventually produced a complex suite of characters which define modern humans. More specifically Hawks points to the archaeological record that suggests contacts all across the continent, which would also likely mediate gene flow from different African hominin groups. This is set as a counterpoint to the classic “African Eve” narrative, informed by mtDNA, in the 1980s. This model is illustrated by an explosion from a small East African group 50 to 100 thousand years ago, as it swept across the continent, and then the world. Today, we know the reality was more complex, and Hawks presents a reasonable contrast in perspective.


The most recent evidence, informed by genomics, indicates that the migration out of Africa was the major bottleneck. Within Africa the situation is less clear. Hawks thesis of a sort of multi-regionalist network of hominin lineages may be correct. In fact much of human evolutionary may be characterized by a series of alternating phases of multi-regional evolution mediated by gene flow and admixture, along with rapid demographic expansions whereby one lineage overwhelms the others (much of this may be due to cultural changes and inter-group dynamics). This is a complicated model, and hard to render in TV-friendly units of consumption. I feel for the producers of First Peoples.

Which brings me to a quibble about the America episode. Overall I really enjoyed how they framed the slow erosion of the Clovis overkill hypothesis. I’ll be honest that the “unveiling” of the Kennewick Man results, which suggest that he was the ancestor of modern groups in the region, was overly dramatic for me. But the biggest issue I had is that it oversimplifies the peopling of the Americas. It does seem that the New World was predominantly populated by the first wave out of Berengia, but there is also genetic evidence that later waves were significant, even in the Kennewick results themselves!

First Peoples is worth watching. Definitely a step forward, as they put a lot of new concepts in front of the general public. But everyone is still figuring things out, the science, and how to present it to people. I’d say that you just have to remember this is an alpha version, and if you want to know the whole story you had better do your follow up.

* Let me be clear here that I understand that some prejudice should be given to the African phenotypes as being more likely, as that continent was the ancestral home with particular environmental conditions which have not varied. And, Oceanians have admixture from other hominin lineages. But to me the priors are not such that the case is overwhelming. Ancient modern humans may have looked nothing like any extant population!

• Category: Science • Tags: First Peoples, Human Evolution 
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12918295 Sometimes it is useful to enter into the record what you think, even if it is not fully formed, or even not strongly held. After reading a review on mutational load in human populations, which lingered long over demographic inferences of our species’ fluctuations in population size, as well as conversations with Gregory Cochran and Ian Mathieson, I have come to the conclusion that cultural group selection is a very important, perhaps dominant, dynamic in explaining the ubiquity of anatomically modern humans over the past ~50,000 years.

This is not a novel position. A group of evolutionary theorists, most prominently today David Sloan Wilson, have argued for the primacy of group level collective dynamics for human societies which allow for a plausible organismic metaphor in their action and behavior for the past 40 years. Peter Richerson and Robert Boyd have developed an extensive body of theoretical work outlining precise models (see Not by Genes Alone) which extend this framework. Importantly, I want to be careful and qualify that I am being precise when I limit my conjecture to humans, and, cultural phenotypes. For empirical and theoretical reasons I believe that humans may be sui generis.

My intuition here is tied in to what I have stated earlier about Aurignacian populations, and their likely extinction in Europe due to the arrival of Gravettian populations. The ancient DNA results are yielding to the conclusion that the human past has been subject to a great deal of local population replacement. To me this is peculiar, because even in the course of inter-group competition one would expect a fair amount of admixture, as is assumed in a demic ‘wave of advance,’ where populations push forward their range through natural increase. In fact the replacements don’t strike me as typically genetical in their fluctuations. Rather, they’re cultural. Punctuated. Alternating between stasis and rapid switches in state and character. The genetic data may simply be witness to the outcomes of winner-take-all outcomes.

Of course there has long been speculation that the social organizations of anatomically modern humans was the key for why they replaced their cousins. Many of these models though were derived from conjecture, and extrapolation. The new twist for me is that the historical population genetics is now aligning with this possibility. These are real concrete data and results.

• Category: Science • Tags: Human Evolution 
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Blue variant derived, correlated with higher anueploidy rates

A quick follow up to my previous post. To recap, a new paper in Science reports high (20-40%) derived frequencies for an allele which seems correlated with higher rates of aneuploidy. Anueploidy is bad, because often it results in nonviable offspring (individuals with Down syndrome have a viable anueploidy). The strange thing about this region of the genome is that it looks like modern humans have harbored this variant since the divergence from Neandertals. But, it has not gone to fixation. Its frequency in the intermediate range all this time, segregating in pretty much all populations from what it looks like, suggests balancing selection.

41ePHetk1dL._SY344_BO1,204,203,200_ Most of the paper is focused on medical genetics and the genome-wide association. The evolutionary aspect is interesting, but struck me as something of an afterthought. I made some chit-chat with the first author at the Bay Area Population Genomics meeting last December, and he didn’t let on that he had any good idea for why this allele was persisting. So I doubt that the group is wedded to the idea that miscarriage is a strategy for masking paternity and encouraging male investment. I’ve asked around people who work in behavioral ecology and they’re skeptical too. There’s a mystery here, and it’s kind of a big deal in my opinion, but there’s not much clarity.

On Twitter Vincent Lynch pointed out that the locus in question, PLK4, has been implicated in testes development. So one possible answer that crops up is that it is some form of sexually anatongistic selection. Meanwhile, Greg Cochran posits that we’re seeing some sort of meiotic drive, where there is selection pressure operating on the level of the genome itself (e.g., “selfish genetic elements” type dynamics). These are both plausible to me, and suggest that there needn’t be an explanation rooted in our human uniqueness to answer this particular genomic mystery.

hominids A common tendency among genomicists, who are modern humans, is to always highlight variants which have been selected in our lineage in comparison to nearby lineages. Before ancient DNA this usually meant chimpanzees, but now we’re talking Neandertals and Denisovans. Humans are a pretty big deal, and intuitively we think that our genomics are also a pretty big deal. There must be a key that unlocks our uniqueness, so searching through the 3 billion base pairs in our genome we stumble upon distinctive evolutionary histories, and think “eureka, this is It, the ultimate locus of our genius!” In pre-modern language, our souls. But the fact is that over tens of millions of polymorphisms in the genome you are naturally going to find regions where we are unique in relation to our relatives, and the broader mammalian family tree, just as a matter of chance. If we lived in the world of the Neanderthal Parallex no doubt Neandertal genomicists would be engaging in the same search for the uniqueness of their lineage, and discover regions where they are sui generis in relation to other hominins and mammals more broadly. The few times I’ve been to ASHG I stumble onto talks where the authors present evidence of genomic regions which are unique in our species, the implication being that this might be somehow responsible for the nature of who we are. Of course the researchers in question are usually not interested in that topic that much, rather, it is an interesting side element that adds to the sexiness of their results, and the glamour usually fades over time.

There is the quest for the the gene for everything. It’s a major problem with media representations of behavior genetics. But a lot of interesting traits are polygenic. We’ve long known this from classical genetics, and genomics is confirming this. There’s not a gene for anything, but a host of genes. Quantitative genetics is banal, but it is powerful. We need to be more open to the possibility that humanity as we understand it isn’t a clear and distinct thing, but the end of a distribution of possibilities long pregnant in our lineage of apes.

• Category: Science • Tags: Genetics, Human Evolution 
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The above figure is from Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos. The author has presented this work at meetings, so I knew it was pending. One of major angles here is that you now have an actionable genotype whereby one can make calculations of likelihood of aneuploidy.. If you are female, and have a 23andMe account, just click here. In accord with the results above the risk for aneuploidy is as follows AA > AG > GG. If you don’t have access, the supplements have a lot of interesting stuff. There you can see that there’s no discernible geographical distribution of the minor allele, which is present in ranges from 20 to 40 percent (here it is at the 1000 Genomes Browser).

From an evolutionary perspective the strange thing is that the derived allele seems to reduce reproductive potential. Neandertals don’t carry the derived variant. But the presence of this derived allele isn’t a coincidence, the authors detect an ancient selection event around this region. So either the variant is beneficial in some way, or, aneuploidy as a trait has hitchhiked. I’ll post the explanation in the paper here, because I honestly don’t even know what to say:

The fact that the haplotype bearing the derived allele did not sweep to fixation and is present at similar frequencies across human populations is consistent with the action of long-term balancing selection. We speculate that the mitotic-error phenotype may be maintained by conferring both a deleterious effect on maternal fecundity and a possible beneficial effect of obscured paternity via a reduction in the probability of successful pregnancy per intercourse. This hypothesis is based on the fact that humans possess a suite of traits (such as concealed ovulation and constant receptivity) that obscure paternity and may have evolved to increase paternal investment in offspring (24). Such a scenario could result in balancing selection by rewarding evolutionary “free riders” who do not possess the risk allele—and thus do not suffer fecundity costs—but benefit from paternity confusion in the population as a whole

Whatever is happening is very strange. The authors make the case that there ascertainment bias is such that they’re underestimating effect of the derived variant. All things equal the selection coefficient should be strongly negative.

• Category: Science • Tags: Genetics, Human Evolution 
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Is ADSL the locus of human genius?

God knows I would sleep more if it weren’t for bioRxiv. A new single author preprint debuts a new method, 3P-CLR, which extends XP-CLR, as a method to detect natural selection. The key is that it uses an explicit three-population tree to pick up selection events after the most recent, and second most recent, divergence events. So in the tree of ((Eurasians , Africans)Archaic Humans), this method can pick up perturbations which suggest selection after the emergence of a coherent anatomically modern population, but before it differentiated into its gorgeous mosaic.

In any case, the most recent version of the preprint, Testing for ancient selection using cross-population allele frequency differentiation:

A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality, and finding which model is most compatible with the data. Chen et al. (2010) developed a composite likelihood method called XP-CLR that uses an outgroup population to detect departures from neutrality which could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method – called 3P-CLR – outperforms XP-CLR when testing for selection that occurred before two populations split from each other, and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Africans and Eurasians, but after their split from Neanderthals, and that could have presumably led to the fixation of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans and the ancestors of both populations, after their split from Africans.

The software will be posted on the author’s github when the manuscript is accepted somewhere.

A minor note is that the data set used was from the 1000 Genomes. The Sub-Saharan Africans then are not from the hunter-gatherer populations, the Khoisan and the Pygmy, who seem to have the largest reservoir of genetic variation. The figure above is from a major signal of selection which is specific to modern humans, but excluded from the Neandertal populations. That is, fixed in us for a derived mutation, fixed in our cousins for the ancestral type (ancestral as judged by reference to the chimpanzee outgroup). My main curiosity is to push the three-population model so that it is ((Khoisan, non-Khoisan)Archaic Humans). I know from ASHG that there are now a fair amount of good quality whole genomes from African hunter-gatherers, so no doubt people are looking for these signatures.

The holy grail here for some geneticists (e.g., Svante Paabo) is to find that gene or genes which changed in us to make us sui generis. I no longer believe that this will ever be found. Assuming tens of millions of polymorphisms floating around in the genome no doubt candidate genes will emerge, just like FOXP2 did all those years ago. But I no longer believe that there is a necessary or sufficient genetic variant for our humanity. It’s a quantitative trait, and many of the hominin lineages were actually stumbling in the same direction.

On a more optimistic note, those of us who work on non-human genomes will also have data sets to rival those who are savants of humanics in the near future, so these methods are generally useful.

Citation: Testing for ancient selection using cross-population allele frequency differentiation, Fernando Racimo, bioRxiv doi:

• Category: Science • Tags: 3P-CLR, Human Evolution, Selection 
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Citation: Craniofacial Feminization, Social Tolerance, and the Origins of Behavioral Modernity Author(s): Robert L. Cieri, Steven E. Churchill, Robert G. Franciscus, Jingzhi Tan, and Brian

Citation: Craniofacial Feminization, Social Tolerance, and the Origins of Behavioral Modernity
Author(s): Robert L. Cieri, Steven E. Churchill, Robert G. Franciscus, Jingzhi Tan, and Brian

Increased brain size across Homo. Luke Jostins

Increased brain size across Homo. Luke Jostins

Humans are a pretty big deal. I’m human, you’re human. We’re a very successful large mammal. A substantial proportion of the earth’s biomass is us, or, is due to us. So the field of human paleoanthropology gets a lot of attention in comparison to something like materials science, even though materials science is far more practical, and a much bigger deal in our day to day life. Most people have heard the name Richard Leakey. They might not even know there’s a field called materials science.

Because people are interested in paleoanthropology there’s a demand for discoveries, and people promising understanding. The root of a lot of this is ontological. Why us? Necessarily us? But more prosaically many scholars have responded by generating models of the rise of humanity with silver bullet explanations. To give a few examples, fire, tools, gossip, and meat. One phenomenon that has interested scientists for years is the rise to dominance of an African lineage 50,000 years ago, and the subsequent manifestation of “behavioral modernity” in the archaeological record. To illustrate behavioral modernity researchers might present you with the image of ostrich shells which may have been painted, or the artistic caves of France and Spain. I think it is simply enough to contrast behavioral modernity with what came before. The Acheulean tool culture persisted for over 1 million years. Can you imagine a cultural tradition today persisting for 10,000 years? Obviously something changed.

One elegant model proposed by the paleoanthropologist Richard Klein is that human culture is a product of a punctuated evolutionary change, which resulted in a revolution in capacities, and a rapid marginalization of all other populations. The phenotypic manifestation of that neurological shift may have been the capacity for fully featured language. In this scenario the chasm between archaic and modern human populations is enormous. At the opposite extreme you have theories which posit a gradual shift across the Homo lineage over time, with behavioral modernity being only the latest manifestation of a trajectory which was initiated long ago. A possible implication in this framework is that something like us was inevitable at some point, or, the Homo lineage would just go extinct (yes, we are going to go extinct at some point in any case).

In 2005 or so I would probably have been close to the Klein model of relatively quick biological driven changes that gave rise to H. sapiens. Today I am much nearer the second scenario. One of the reasons is that a few years back the geneticist Luke Jostins produced the result that Homo as a whole was undergoing encephalization. To some extent this is obvious in hindsight. Neanderthals had larger brains than their ancestors. But Jostin’s plot suggested to me that the path which led to our big brained lineage had roots somehow early on in the emergence of our broader lineage, and not just in the recent past of H. sapiens sapiens. Only that could explain a world wide pattern across disparate lineages which were genetically isolated. I don’t have a specific outline of what I’m thinking of, but in the generality there are cases where evolutionary processes exhibit path dependence. One could argue then that Homo was going to get big brained, or go extinct. We do know that apes as a whole have been less successful in the evolutionary game if being speciose is a guide over the Cenozoic. Monkeys have taken over many of the niches which were previous held by the apes. There used to many more of us. Homo is then the exception to the rule, as it broke out of the niche which monkeys were taking over, and made lemonade from lemons.

So how might this inevitable process have played out? As implied in the title I suspect that early in the Pleistocene Homo got “trapped” in a unidirectional ratchet where biological changes allowed for the elaboration of complex culture, which then drove further biological changes, again resulting in culture transformations, and so forth. The evolutionary process did not explore the whole parameter space with equal frequency. H. floresiensis stumbled upon a unique, but rare, niche (you can speculate about what it was, but its small size and peculiar anatomy indicate sit differed from others of the lineage quite a bit in its circumstances). In contrast other groups of Homo were getting bigger brained. In fact the shift toward bigger brains leveled off at about ~100,000 years ago, before behavioral modernity. This is probably a consequence of the fact that there are various biological limits in terms of how disproportionate our brains and heads can be in relation to the rest of our bodies (e.g., we are born at a rather fetal stage because otherwise our heads would get too large to fit through the birth canal, whose widening is achieved at some cost to female locomotion). At yet changed continued.

A new paper in Current Anthropology attempts to bring various threads together to explain the rise of modern humans in a manner Charles Darwin would appreciate, Craniofacial feminization and the origin of behavioral modernity. Like most of you I can see that the figure above at the top of this post illustrates two individuals where one is more gracile or feminized than the other. But that’s about it. I don’t know skeletal anatomy well enough to comment with great force on the data within the paper, though it does seem that the results are somewhat confused, with data scarcity and combining agriculturalists and foragers in the Holocene confounding the signal. Nevertheless, they conjecture is that over the past 100,000 years humans have been subject to the domestication syndrome. Less aggressive social behavior at higher densities due to reduction in androgen levels produces the more feminine features in the fossil record. At least according to their model.

The major problems I have is that the signal in their data is not that clear to me. There is a lot of talk about why agriculturalists seem more masculinized than Holocene foragers. Obviously that sort of result is not as “neat” as they might like across the time period of interest. They acknowledge that limitations on their data set might explain this, but that makes me wonder what conclusions they can draw then in the first place from their data. Or, their model is just too simple. It’s a bit rich for me to say that, because compared to Richard Klein’s thesis that one mutation produced modern human behavior the argument outlined in exceedingly elaborate. But, if behavioral modernity arose via processes which were gradual, and often worked upon standing genetic variation, I don’t see why the selection should have been through the same processes across hundreds of thousands of years. It could be that in some epochs higher population density was due to biological changes in humans triggered by culture shifts, while in other phases the higher density itself was driving biological change. This is not congenial from a scientific perspective because it isn’t parsimonious. But it isn’t wrong on the face of it.

• Category: Science • Tags: Human Evolution 
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Citation: Zerjal, Tatiana, et al. "The genetic legacy of the Mongols." The American Journal of Human Genetics 72.3 (2003): 717-721.

Citation: Zerjal, Tatiana, et al. “The genetic legacy of the Mongols.” The American Journal of Human Genetics 72.3 (2003): 717-721.

The above is a figure from The genetic legacy of the Mongols, and illustrates the concept of a “star-shaped phylogeny.” This is basically a phenomenon where a massively rapid demographic expansion of one particular lineage results in a host of nearly simultaneously mutational events which derive from the ancestral state. It is illustrated by the topology above, where derived states cluster around the ancestral type. Obviously it is harder to characterize the sequential structure of lineage fissions in these circumstances.

I am beginning to think that some of the same issues may apply to the expansion of Homo sapiens sapiens 40 to 60 thousand years. The thought was triggered by the recent abstract at SMBE 2014 on the 45 thousand year old Siberian which was whole genome sequenced:

The complete genome sequence of a 45,000-year-oldmodern human from Eurasia

We have sequenced to high coverage the genome of a femur recently discovered near Ust-Ishim in Siberia. The bone was directly carbon-dated to 45,000 years before present. Analyses of the relationship of the Ust-Ishim individual to present-day humans show that he is closely related to the ancestral population shared between present-day Europeans and present-day Asians. The over-all amount of genomic admixture from Neandertals is similar to that in present-day non-Africans and there is no evidence for admixture from Denisovans. However, the size of the genomic segments of Neandertal ancestry in the Ust-Ishim individual is substantially larger than in present-day individuals. From the size distribution of these segments we estimated that this individual lived about 200-400 generations after the admixture with Neandertals occurred. The age of this genome allows us to directly assess the mutation rate in the different compartments of the human genome. These results will be presented and discussed.

200-400 generations means 5 to 10 thousand years. So the implication is that the admixture event which led to the Neandertal ancestry in non-Africans dates to 50 to 55 thousand years before the present. Australia was settled by modern humans ~45 thousand years before the present, while western Europe was settled ~35 thousand years before the present. Ancient DNA from China 40 thousand years ago already suggests that East Eurasians had begun to diverge as an independent lineage. Joe Pickrell says that when he saw the poster the ancient Siberian seemed more closely related to one of the two dominant Eurasian lineages. I suspect it would be to West Eurasians, as the Ma’lta Paleo-Siberian from 22 thousand years ago was. Overall the picture seems to be that many of the ancestral lineages which are geographically distinct across Eurasia and Oceania had already come into being in the interval between the admixture even with Neandertals 55 thousand years ago the 45 thousand year old Siberian. Because these lineages diverged so rapidly in sequence you see a situation where sometimes have polytomies, where the phylogeny can not be fully resolved. With the emergence of ancient DNA and whole genome sequences I believe that this issue will mostly be overcome, but, it explains why different methods of inference have given someone different results (e.g., the old question with Oceanians are an outgroup to Eurasians or more similar to East Eurasians).

Finally, there’s the issue why these neo-Africans were so rapid in their spread and demographic dominance ~50 thousand years ago. Probably the dominant position, most forcefully articulated by Richard Klein in The Dawn of Human Culture, is that Homo sapiens sapiens has biological competencies which allowed them to marginalize other hominins. This is obviously one reason that some geneticists are trying to find specific differences between the genomes of our own lineage and that of our cousins. But if researchers focused on modern human lineages they wouldn’t present a biological explanation at all, but a cultural one. How do you set up your priors? Because many people presumed that the emergence of sapiens sapiens was a speciation event it seemed that a biological explanation was more plausible. I don’t deny that that’s the case, and that we should weight cultural explanations more strongly when it comes to something like the Austronesian expansion (first, the genetic difference between Austro-Asiatic Southeast Asians and Austronesians is not that great at all). But perhaps we shouldn’t dismiss the possibility of some cultural innovation as being the root of the neo-African advantage? I believe we need to start thinking more systematically about the expansions of hominin lineages since the early Pleistocene.

• Category: Science • Tags: Genetics, Genomics, Human Evolution 
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A new paper posted on bioArxiv surveys Y chromosomal and mtDNA diversity using over 600 males from the HGDP data set. Their goal is to compare differences in variation and long term demography between the two sexes. This is not an unimportant topic, sex specific demographics are relevant to mating patterns, and effective population size is of broader evolutionary interest in the way they can frame different dynamics. For instance, species with high male reproductive skew and genetic polygyny tend to be subject to more powerful sexual selection, as males have a much larger potential upper reproductive bound (a phenomenon which drives greater sexual dimorphism). This sort of evaluation with the Y and mtDNA has been attempted before, but the power of this data set is greater because they have a much larger fraction of the Y chromosome (500 kilobases) and whole mtDNA genomes (often in the past they used STRs for the Y and only the HVR in the mtDNA). These data from 600 males allowed them to construct the figure you see above, which shows the branching pattern of human migration out of Africa at given time periods, male and female effective population sizes, and later expansions (female red, male blue).

Even accounting for the possible smaller effective population sizes of uniparental lineages due to greater drift (haploid inheritance cuts down the pool of parents) I am struck again by the shockingly small number of inferred individuals who left Africa. It does not seem unreasonable to give a number closer to 100 as opposed to 1,000 for the ur-population which settled the world outside of Africa, at least when it comes to the neo-African ancestry (i.e., excludes the residual archaic admixture). But is the answer so simple? What I’m primarily concerned with is the treelike representation of human migration above. It is highly likely that less than half of the ancestry of modern Europeans dates to the original settlement date given above. So those inferred male and female effective population sizes need to be taken with a grain of salt. Much the same can be said for elsewhere. Additionally, there may have been two Out-of-Africa events in close succession (here I’m alluding to ‘basal Eurasian’ vs. the ancestors of western and eastern Eurasians proper).

Overall I can accept the broad picture painted of greater female effective population sizes, and the rise in reproductive skew in the more recent past is intriguing, and dovetails with particular conjectures of some anthropologists and economists (i.e., a rise of “winner-take-all” stratification). And the small effective population sizes at particular bottleneck events is broadly creditable looking at genome-wide patterns (e.g., high sequence level diversity in Africa vs. non-Africa). But these surveys need more textured detail in this data and age. I hope later revisions will flesh that out, as well as acknowledge the findings of Sayres et al.

Citation: Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences, Sebastian Lippold, Hongyang Xu, Albert Ko, Mingkun Li, Gabriel Renaud, Anne Butthof, Roland Schroeder, Mark Stoneking, bioRxivdoi: 10.1101/001792

• Category: Science • Tags: Human Evolution 
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A new paper in Nature fleshes out some details about the relationships between Denisovans, Neanderthals, and modern humans, as well as possible others. I believe the figure above gives the flavor of the general findings in terms of phylogenetics, though if you want more I recommend Carl Zimmer in The New York Times. It has to be noted that it’s incredible that such high resolution sequencing could be done on these ancient fossils, when ~10 years ago we were excited about one modern genome. Also, I am struck by, though not surprised, that it doesn’t seem to be that modern humans (our lineage) had too many distinctive major genetic differences from our cousins. Finally, it does seem that the human phylogeny is more properly defined as a graph than a tree. But don’t forget that it doesn’t seem like all the edges were weighted the same. We’re a whole lot more Neo-African than we are Neanderthal or Denisovan.

• Category: Science • Tags: Evolution, Human Evolution 
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Likely an individual with derived allele on KITL locus (Credit: David Shankbone)

An individual polymorphic on the KITL locus? (Credit: David Shankbone)

Pigmentation is one of the few complex traits in the post-genomic era which has been amenable to nearly total characterization. The reason for this is clear in hindsight. As far back as the 1950s (see The Genetics of Human Populations) there were inferences made using human pedigrees which suggested that normal human variation on this trait was controlled by fewer than ten genes of large effect. In other words, it was a polygenic character, but not highly so. This means that the alleles which control the variation are going to have reasonably large response, and be well within the power of statistical genetic techniques to capture their effect.

I should be careful about being flip on this issue. As recently as the mid aughts (see Mutants) the details of this trait were not entirely understood. Today the nature of inheritance in various populations is well understood, and a substantial proportion of the evolutionary history is also known to a reasonable clarity as far as these things go. The 50,000 foot perspective is this: we lost our fur millions of years ago, and developed dark skin, and many of us lost our pigmentation after we left Africa ~50,000 years ago (in fact, it seems likely that hominins in the northern latitudes were always diverse in their pigmentation)

A new paper in Cell sheds some further light on the fine-grained details which might be the outcome of this process. Being a Cell paper there is a lot of neat molecular technique to elucidate the mechanistic pathways. But I will gloss over that, because it is neither my forte nor my focus. A summary of the paper is that it shows that p53, a relatively well known tumor suppressor gene, seems to have an interaction with a response element (the gene product binds in many regions, it is a transcription factor) around the KITLG locus. This locus is well known in part because it has been implicated in pigment variation in human and fish. So KITLG is one of the generalized pigmentation pathways which spans metazoans. There are derived variants in both Europeans and East Asians which are correlated with lighter skin, though there is polymorphism in both cases (it has not swept to fixation).

The wages of adaptation? (Credit: Hoggarazzi Photography)

The wages of adaptation? (Credit: Hoggarazzi Photography)

But this is a Cell paper, so there has to be a more concrete and practical angle than just evolution. And there is. It turns out that a single nucleotide polymorphism mutation in the p53 response element results in a tendency toward upregulation of KITLG and male germ line proliferation. The latter matters when it comes to tumor genesis, and in particular testicular cancer. This form of cancer is one where there doesn’t seem to be a somatic cell mutation of p53 itself. Additionally, the authors observe that testicular cancer manifests at a 4-5 fold greater rate in people of European descent than African Americans. And, presumably the upregulation of KITLG is somehow related to increased melanin production. The authors posit that because of lighter skin in Europeans due to selection at other loci there has been a balancing effect at KITLG (increased tanning response). There is evidence of selection at this locus (a long haplotype and increased homozygosity), so this is not an unreasonable conjecture, though the high frequency of loss of function alleles suggests that the model is likely complex.

I don’t know if this particular story is correct in its details (though I am intrigued that variation in KITLG is associated with cancer in other organisms). But it illustrates one of the possible consequences of rapid evolutionary change due to human migration out of Africa: deleterious side effects because of pleiotropy. In other words, as you tinker with the genomic architecture of a population you are going to have to accept tradeoffs as you are optimizing one aspect of function. Genes don’t have just one consequence, but are embedded in myriad pathways. Over time evolutionary theory predicts a slow re-balancing, as modifier genes arise to mask the deleterious side effects. But until then, we will bear the burdens of adaptation as best as we can.

Citation: Zeron-Medina, Jorge, et al. “A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection.” Cell 155.2 (2013): 410-422.

(Republished from Discover/GNXP by permission of author or representative)
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Layers and layers….

There is the fact of evolution. And then there is the long-standing debate of how it proceeds. The former is a settled question with little intellectual juice left. The latter is the focus of evolutionary genetics, and evolutionary biology more broadly. The debate is an old one, and goes as far back as the 19th century, where you had arch-selectionists such as Alfred Russel Wallace (see A Reason For Everything) square off against pretty much the whole of the scholarly world (e.g., Thomas Henry Huxely, “Darwin’s Bulldog,” was less than convinced of the power of natural selection as the driving force of evolutionary change). This old disagreement planted the seeds for much more vociferous disputations in the wake of the fusion of evolutionary biology and genetics in the early 20th century. They range from the Wright-Fisher controversies of the early years of evolutionary genetics, to the neutralist vs. selectionist debate of the 1970s (which left bad feelings in some cases). A cartoon-view of the implication of the debates in regards to the power of selection as opposed to stochastic contingency can be found in the works of Stephen Jay Gould (see The Structure of Evolutionary Theory) and Richard Dawkins (see The Ancestor’s Tale): does evolution result in an infinitely creative assortment due to chance events, or does it drive toward a finite set of idealized forms which populate the possible parameter space?*

But ultimately these 10,000 feet debates are more a matter of philosophy than science. At least until the scientific questions are stripped of their controversy and an equilibrium consensus emerges. That will only occur through an accumulation of publications whose results are robust to time, and subtle enough to convince dissenters. This is why Enard et al.’s preprint, Genome wide signals of pervasive positive selection in human evolution, attracted my notice. With the emergence of genomics it has been humans first in line to be analyzed, as the best data is often found from this species, so no surprise there. Rather, what is so notable about this paper in light of the past 10 years of back and forth exploration of this topic?**

By taking a deeper and more subtle look at patterns of the variation in the human genome this group has inferred that adaptation through classic positive selection has been a pervasive feature of the human genome over the past ~100,000 years. This is not a trivial inference, because there has been a great deal of controversy as to the population genetic statistics which have been used to infer selection over the past 10 years with the arrival of genome-wide data sets (in particular, a tendency toward false positives). In fact, one group has posited that a more prominent selective force within the genome has been “background selection,” which refers to constraint upon genetic variation due to purification of numerous deleterious mutations and neighboring linked sites.

The sum totality of Enard et al. may seem abstruse, and even opaque, in terms of the method. But each element is actually rather simple and clear. The major gist is that many tests for selection within the genome focus on the differences between nonynonymous and synonymous mutational variants. The former refer to base positions in the genome which result in a change in the amino acid state, while the latter are those (see the third positions) where different bases may still produce the same amino acid. The ratio between substitutions, replacements across lineages for particular base states, at these positions is a rough measure of adaptation driven by selection on the molecular level. Changes at synonymous positions are far less constrained by negative selection, while positive selection due to an increased fitness via new phenotypes is presumed to have occurred only via nonsynonymous changes. What Enard et al. point out is that the human genome is heterogeneous in the distribution of characteristics, and focusing on these sorts of pairwise differences in classes without accounting for other confounding variables may obscure dynamics on is attempting to measure. In particular, they argue that evidence of positive selective sweeps are masked by the fact that background selection tends to be stronger in regions where synonymous mutational substitutions are more likely (i.e., they are more functionally constrained, so nonsynonymous variants will be disfavored). This results in elevated neutral diversity around regions of nonsynonymous substitutions vis-a-vis strongly constrained regions with synonymous substitutions. Once correcting for the power of background selection the authors evidence for sweeps of novel adaptive variants across the human genome, which had previous been hidden.

There are two interesting empirical findings from the 1000 Genomes data set. First, the authors find that positive selection tends to operate upon regulatory elements rather than coding sequence changes. You are probably aware that this is a major area of debate currently within the field of molecular evolutionary biology. Second, there seems to be less evidence for positive selection in Sub-Saharan Africans, or, less background selection in this population. My own hunch is that it is the former, that the demographic pulse across Eurasia, and to the New World and Australasia, naturally resulted in local adaptations as environmental conditions shifted. Though it may be that the African pathogenic environment is particularly well adapted to hominin immune systems, and so imposes a stronger cost upon novel mutations than is the case for non-Africans. So I do not dismiss the second idea out of hand.

Where this debate about the power of selection will end is anyone’s guess. Nor do I care. Rather, what’s important is getting a finer-grained map of the dynamics at work so that we may perceive reality with greater clarity. One must be cautious about extrapolating from humans (e.g., the authors point out that Drosophila genomes are richer in coding sequence proportionally). But the human results which emerge because of the coming swell of genomic data will be a useful outline for the possibilities in other organisms.

Citation: Genome wide signals of pervasive positive selection in human evolution

* The cartoon qualification is due to the fact that I am aware that selection is stochastic as well.

** Voight, Benjamin F., et al. “A map of recent positive selection in the human genome.” PLoS biology 4.3 (2006): e72., Sabeti, Pardis C., et al. “Detecting recent positive selection in the human genome from haplotype structure.” Nature 419.6909 (2002): 832-837., Wang, Eric T., et al. “Global landscape of recent inferred Darwinian selection for Homo sapiens.” Proceedings of the National Academy of Sciences of the United States of America 103.1 (2006): 135-140., Williamson, Scott H., et al. “Localizing recent adaptive evolution in the human genome.” PLoS genetics 3.6 (2007): e90., Hawks, John, et al. “Recent acceleration of human adaptive evolution.” Proceedings of the National Academy of Sciences 104.52 (2007): 20753-20758., Pickrell, Joseph K., et al. “Signals of recent positive selection in a worldwide sample of human populations.” Genome research 19.5 (2009): 826-837., Hernandez, Ryan D., et al. “Classic selective sweeps were rare in recent human evolution.” Science 331.6019 (2011): 920-924.

(Republished from Discover/GNXP by permission of author or representative)
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Credit: Ryan Somma

Like many people I’ve been following the tales of the Hobbits of Flores, H. floresiensis, with some interest since 2004. And, like most people I have no personal expertise or skill which is relevant to evaluating whether this putative hominin species actually is a new species (as opposed to a pathological modern human). So how are we to evaluate a new PLOS ONE article which comes down on the side that it is a new species? First, my very vague impression is that over the past ~10 years the new-species camp has been gaining ground on the pathological-modern-human set. But setting all that aside perhaps the critical issue for me is that the likely reality of archaic human admixture into our own lineage means that the world is far stranger than we had thought in 2004. For various anatomical and paleoanthropological reasons H. floresiensiswas implausible. But as implausible as the idea that the genome of a Siberian hominin would yield admixture in modern Papuans?

Addendum: New York Times on the paper in PLOS ONE.

(Republished from Discover/GNXP by permission of author or representative)
• Category: Science • Tags: Anthropology, Hobbit, Human Evolution 
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As recently as 10 years ago one could plausibly talk about mtDNA Eve and Y chromosomal Adam. The “Human Story” might then be stylized into a rapid expansion from a small core East African population which flourished ~100,000 years ago, and engaged in a jailbreak sweep out of Africa and across the rest of the World Island, and beyond, to Oceania and the New World. In the process all other human lineages extirpated, marginalized, and eliminated, their culture and genes consigned to oblivion. No longer, the origin of our species may have been characterized by several admixture events with “other” lineages, both within, and outside of, Africa. Instead of a bifurcating tree, imagine a graph with reticulation. A phylogenetic tree with a light, but noticeable lattice scaffold, tying together disparate branches.

All this must be kept in mind when we see a paper such as An African American Paternal Lineage Adds an Extremely Ancient Root to the Human Y Chromosome Phylogenetic Tree. The authors discovered a Y chromosomal lineage, A00, which diverges on the order of ~338,000 years before the present from other extant paternal lineages (the next oldest divergence is A0, ~200,000 years before the present. The 95% interval is 237 to 581 thousand years. Even taking the lower bound this implies that this Y chromosomal lineage diverged from the others before the emergence of anatomically modern humans in Africa ~200,000 years ago.

This sort of result is not about ingenious method or deep insight, but the reality that thick, dense, and expansive population coverage is going to uncover interesting and insightful detail. Though these basal Y (and mtDNA) lineages tend to be found in African hunter-gatherers, A00 is present among Bantu and West African populations. The simplest explanation is that A00 represents at case of genetic admixture between the dominant root lineage to our own species, as a collateral branch. In light of all that we know about genetics and paleontology now this is not entirely surprising. Rather, my question is simple: why is it that we have not found similar Y and mtDNA lineages in non-African populations?

Cite: Mendez et al., doi:10.1016/j.ajhg.2013.02.002

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There’s an excellent paper up at Cell right now, Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. It synthesizes genomics, computational modeling, as well as the effective execution of mouse models to explore non-pathological phenotypic variation in humans. It was likely due the last element that this paper, which pushes the boundary on human evolutionary genomics, found its way to Cell (and the “impact factor” of course).

The focus here is on EDAR, a locus you may have heard of before. By fiddling with the EDAR locus researchers had earlier created “Asian mice.” More specifically, mice which exhibit a set of phenotypes which are known to distinguish East Asians from other populations, specifically around hair form and skin gland development. More generally EDAR is implicated in development of ectodermal tissues. That’s a very broad purview, so it isn’t surprising that modifying this locus results in a host of phenotypic changes. The figure above illustrates the modern distribution of the mutation which is found in East Asians in HGDP populations.

One thing to note is that the derived East Asian form of EDAR is found in Amerindian populations which certainly diverged from East Asians > 10,000 years before the present (more likely 15-20,000 years before the present). The two populations in West Eurasia where you find the derived East Asian EDAR variant are Hazaras and Uyghurs, both likely the products of recent admixture between East and West Eurasian populations. In Melanesia the EDAR frequency is correlated with Austronesian admixture. Not on the map, but also known, is that the Munda (Austro-Asiatic) tribal populations of South Asia also have low, but non-trivial, frequencies of East Asian EDAR. In this they are exceptional among South Asian groups without recent East Asian admixture. This lends credence to the idea that the Munda are descendants in part of Austro-Asiatic peoples intrusive from Southeast Asia, where most Austro-Asiatic languages are present.

And yet one thing that jumps out at me is that there is no East Asian EDAR in European populations, even in Russians. I am a bit confused by this result, because of the possibility of Siberian-affiliated population admixture with Europeans within the last 10,000 years, as adduced by several researchers (this is not an obscure result, it manifests in TreeMix repeatedly). The second figure shows the inferred region from which the East Asian EDAR haplotype expanded over the past 30,000 years. The authors utilized millions of forward simulations with a host of parameters to model the expansion of EDAR, so that it fit the distribution pattern that is realized (see the supplements here for the parmeters). To make a long story short they infer that there was one mutation on the order of ~30,000 years before the present, and that it swept up in frequency driven by selection coefficients on the order of ~0.10 (10% increase relative fitness, which is incredibly powerful!). This is on the extreme end of selective sweeps, and likely of the same class as the haplotype blocks which characterize SLC24A5 and LCT (the block is shorter, though that makes sense because of the deeper time depth). Again, I am perplexed why such an ancient allele, which is found in Amerindians, or Munda populations, is absent in Europeans who have putative East Eurasian admixture. The whole does not cohere for me. There is a weak point in one or more of my assumptions.

Then there’s the section on the mouse model. To me this aspect was ingenious, though I’m not particularly able to assess it on its technicalities. The earlier usage of mouse models to test the effects of mutations on EDAR was in the context of coarse copy number changes which resulted in massive dosage changes of protein. The phenotypic outcomes were rather extreme in that case. Here they used a “knockin” model where they recreated the specific EDAR point mutation. Instead of extreme phenotypes they found that the mice were much more normal in their range of traits, though the hair form shifts were well aligned with what occurred in humans. Additionally there were some changes in the number of eccrine glands, with a larger number in the derived East Asian EDAR carriers (with additive effect). Finally they noticed that there were differences in mammary gland pad area and branching. None of this is that surprising, EDAR is a significant regulatory gene which shapes the peripheries and exterior of an organism.

To double check the human relevance of what they found in the mouse model they performed a genome-wide association in a large cohort of Han Chinese. The correlations of particular traits were in the directions that they expected; those individuals with East Asian EDAR variants had thicker hair, shovel-shaped incisors, and a greater density of eccrine glands. It is perhaps important to note that the frequency of the derived variant is so high in Han populations that they didn’t have enough homozygote ancestral genotypes to perform statistics, so their comparisons involved heterozygotes with the derived mutant and also a copy of the ancestral state. This is like SLC24A5 in Europeans, where it is difficult to find individuals of European heritage who have double copies of the non-European modal variant.

Let’s review all the awesome things they did in this study. They dug deeply into the evolutionary genomics of the region around the EDAR, concluding that this haplotype was driven up in frequency from on ancestral variant ~30,000 years ago in a hard selective sweep. And a sweep of notable strength in terms of selection coefficient. This may be one of the largest effect targets of natural selection in the genome of non-Africans over the past 50,000 years. Second, they used a humanized mouse model to explore the range of phenotypes correlated with this mutational change in East Asians. So you have a strong selection coefficient on a locus, and, a range of traits associated with changes on that locus. Third, they confirmed the correlation between the traits and the mutation in humans, despite there being prior research in this area (i.e., they reproduced). This is all great science, and shows the power of collaboration between the groups.

Much of the elegance and power of the paper applies to the discussion section as well, but to be frank this is where things start falling apart for me. You can get a sense of it in The New York Times piece, East Asian Physical Traits Linked to 35,000-Year-Old Mutation. The headline here points to a legitimately important inference from this line of research, many salient physical characteristics of the human races seem to be due to strong selection events at a few loci. In addition to EDAR I’m thinking of the pigmentation loci, such as SLC24A5. I wouldn’t be surprised if there was something similar for the epicanthic fold. If it is visible, and defines between populations differences, it is generally not genomically trivial. There’s usually a story underneath that difference.

In the broad scale of human natural history the problem that arises for me is that we have traits, we have genes under selection, but we have very weak stories to explain the mechanism and context of natural selection. Here there is a strong contrast with the loci around lactase persistence and malaria resistance. In those situations the causal mechanism for the selection seems relatively clear. Critics of evolutionary psychology are wont to accuse the field of ‘Just So’ storytelling, but the same problem crops up in the more intellectually insulated domain of evolutionary genomics (in part because the field is very new, and also mathematically and computationally abstruse). To illustrate what I’m talking about I’m going to quote from the discussion of the above paper:

A high density of eccrine glands is a key hominin adaptation that enables efficient evapo-traspiration during vigorous activities such as long-distance walking and running (Carrier et al., 1984; Bramble and Lieberman, 2004). An increased density of eccrine glands in 370A carriers might have been advantageous for East Asian hunter-gatherers during warm and humid seasons, which hinder evapo-transpiration.

Geological records indicate that China was relatively warm and humid between 40,000 and 32,000 years ago, but between32,000 and 15,000 years ago the climate became cooler and drier before warming again at the onset of the Holocene (Wang et al., 2001; Yuan et al., 2004). Throughout this time period, however, China may have remained relatively humid due to varying contribution from summer and winter monsoons.

High humidity, especially in the summers, may have provided a seasonally selective advantage for individuals better able to functionally activate more eccrine glands and thus sweat more effectively (Kuno, 1956). To explore this hypothesis, greater precision on when and where the allele was under selection—perhaps using ancient DNA sources—in conjunction with more detailed archaeological and climatic data are needed.

A climate adaptation is always a good bet. The problem I have with this hypothesis is that modern day gradients in the distribution of this allele are exactly the reverse of what one might expect in terms of adaptation to heat and humidity. Additionally, is there no cost to this adaptation? After the initial sweep upward, the populations where the derived EDAR mutant is found in high frequencies went through the incredible cold of the Last Glacial Maximum, and groups like the Yakuts are known to have cold adaptations today. Not only that, but the Amerindians from the arctic to the tropics all exhibit a cold adapted body morphology, the historical consequence of the long sojourn in Berengia.

Granted, the authors are not so simplistic, and the somewhat disjointed discussion alludes to the fact that EDAR has numerous phenotypic effects, and it may be subject to diverse positive selection pressures. This seems plausible on the surface, but this complexity of mechanism seems ill-fitted to the fact that the signal of selection around this locus is so clean and crisp. It seems that this is not going to be an easy story to unpack, and there’s a good deal of implicit acknowledgement of that fact in this paper. But tacked right at the end of the main text is this whopper:

It is worth noting that largely invisible structural changes resulting from the 370A allele that might confer functional advantage, such as increased eccrine gland number, are directly linked to visually obvious traits such as hair phenotypes and breast size. This creates conditions in which biases in mate preference could rapidly evolve and reinforce more direct competitive advantages. Consequently, the cumulative selective force acting over time on diverse traits caused by a single pleiotropic mutation could have driven the rise and spread of 370A.

A simple takeaway is that the initial climatic adaptation may have given way to a cultural/sexual selective adaptation, whereby there was a preference for “good hair” as exemplified by pre-Western East Asian canons (black and lustrous), as well as a bias toward small breasts. This aspect gets picked up in The New York Times piece of course. I’ll quote again:

But Joshua Akey, a geneticist at the University of Washington in Seattle, said he thought the more likely cause of the gene’s spread among East Asians was sexual selection. Thick hair and small breasts are visible sexual signals which, if preferred by men, could quickly become more common as the carriers had more children. The genes underlying conspicuous traits, like blue eyes and blond hair in Europeans, have very strong signals of selection, Dr. Akey said, and the sexually visible effects of EDAR are likely to have been stronger drivers of natural selection than sweat glands.

The passage here is ambiguous because the author of the article, Nick Wade, doesn’t use quotes, and I don’t know what is Akey and what is Wade’s gloss on Akey. For example, for theoretical reasons of reproductive skew (a few men can have many children) in general sexual selection is considered to be driven most often by female preference for male phenotypes. I assume Akey knows this, so I suspect that that section is Wade’s gloss (albeit, a reasonable one given the proposition of preference for smaller breasts). The main question on my mind is how seriously prominent population geneticists such as Joshua Akey actually take sexual selection to be as a force driving variation and selection in human populations. It seems that quite often sexual selection is presented as a deus ex machina. A phenomenon which can rescue our confusion as to the origins of a particular suite of traits. But our assessment of the likelihood of sexual selection presumably has to be premised on prior expectations informed by a balance of different forces one can gauge from the literature, and here my knowledge of the current sexual selection literature is weak. Perhaps my skepticism is premised on my ignorance, and the population geneticists who proffer up this explanation are more informed as to the state of the literature.

All this brings me back to the farcical title. When this paper first made news last week I was having dinner with a friend of Japanese heritage (who spent his elementary school years in Japan). I asked him point blank, “Do you like small breasts?” His initial response was “WTF!?! Razib,” but as a mouse geneticist he understood the thrust of my question after I outlined the above results to him. From personal communication with many East Asian American males I am not convinced that there is a overwhelmingly strong preference for small breasts within this subset of the population. But the key here is American. These are individuals immersed in American culture. The norms no doubt differ in East Asia. The typical visual representation of celebrity East Asian females that we see in the American media depict individuals who are slimmer and more understated in their secondary sexual characteristics than is the norm among Western female celebrities (e.g., Gong Li, the new crop of Korean pop stars, even taking into account the plastc surgery of the latter). Part of this is no doubt the reality that the normal range of variation across the population differs, and part of it may be the nature of aesthetic preferences.

But the possibility of deep rooted psychological reasons driving sexual selection (to my knowledge there was no culture which spanned South China and Siberia) brings us back to old ideas about the Pleistocene mind. And, it brings us back to evolutionary psychology, a field which is the whipping boy of both skeptics of the utility of evolutionary science in understanding human nature, and rigorous practitioners of evolutionary biology. And yet here it is not the evolutionary psychologists, but rock-ribbed statistical geneticists who I often see being quoted in the media invoking sexual selection. But do we know it is sexual selection, or is it just our best guess? Because more often than not best guesses are wrong (though best guesses are much more likely to be right than worst guesses!).

Evolutionary genomics has come a long way in the past 10 years. We know, for example, the genetic architecture and some aspects of the natural history of many traits. But, there are still shortcomings. Lactase persistence is the exception to the rule. Even a phenotype as straightforward as human pigmentation has no undisputed answer as to why it has been the repeated target of selection across Eurasia over the past 40,000 years. Oftentimes the right answer is simply that we just don’t know.


(Republished from Discover/GNXP by permission of author or representative)
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I have mentioned the PLoS Genetics paper, The Date of Interbreeding between Neandertals and Modern Humans, before because a version of it was put up on arXiv. The final paper has a few additions. For example, it mentions the generally panned (at least in the circles I run in) PNAS paper which suggested that ancient population structure could produce the same patterns which were earlier used to infer admixture with Neandertals (the authors also point to Yang et al. as a support for the proposition of admixture rather than structure). The primary result, dating the admixture between Neandertals and anatomically modern humans ~40-80,000 years before the present, is reiterated.

An interesting aspect is that their method is to utilize linkage disequilibrium (LD) decay. It’s interesting because tens of thousands of years is a hell of a long time to be able to detect an admixture event via LD! In particular because there’s likely a palimpsest effect where there are intervening admixtures and other assorted demographic events (e.g., bottlenecks and selective sweeps can also generate LD). So how’d they do it? Basically the authors figured out a way to ascertain which pairs of SNPs may have introgressed from Neandertals by comparing the frequency in modern humans to Neandertals at those given SNPs (in particular, by looking at variants at low frequency in Africans and derived in Neandertals). A major technical problem here is the “genetic map” which allows one to assess what the nature of recombination over time is going to be which breaks apart the associations which are the hallmark of LD is not particular precise enough to robustly allow them to make the inferences that they want.

The methods which they used to correct for these problems are ingenious and clever, and as is usually the case with this group the supporting information is well worth the read if you are a geneticist. But I am of a mind to recall what Dr. Joseph Pickrell’s statement about the nature of peer review in such specialized and fankly arcane field implied: that the number of genuine peers is relatively small. Unlike physicists or economists most biologists are not formally trained in a common technical mathematical language. This explains the surplus of people from physics and mathematics backgrounds in many genomic laboratories. These are people who can parse and analyze big data, and extract signal from the noise by generating their own statistical tools as needed. But despite the forbidding formal aspect to the methods, the results coming out of these laboratories are still of interest, both academically (scientists are interested in stuff, period) and professionally (scientists like to use the methods that others develop) to those outside the discipline.

And yet I believe that a divergence is developing here, as the methods developers are blazing to cut deep into the swell of data are moving well ahead of where other biologists can follow. Of course it is not just biologists. These particular specific questions about deep history and the human phylogenetic tree is of great interest to paleoanthroplogists, most of whom clearly can not follow with any fluency the debates about ancient structure or admixture, and the relevant of D-statistics. This is clearly what happened when Richard Klein convinced The New York Times to write an article which brought to light his professional gripes with the statistical geneticists who have upturned his nicely situated apple-cart, and offered up a compelling competitor to him in his domain specific specialty. But in Klein’s defense his elegant verbal models were at least clear to the general public. There is a methodological opacity to statistical genomics which we have to admit is undeniable.

Ultimately from my own personal experience there is one primary way to truly grokk what is going on in a paper like this: replicate their analyses with the same computational techniques, and develop one’s own intuition. Unfortunately this takes time, and everyone has their own tasks before them, so less of this happens than should be the case (e.g., thousands of simulations are not cheap computationally). But all groups like the one above can do is provide the software tools, and point to where the data is (this emphasizes the crucial importance of open science today). Others can reanalyze, and importantly replicate simulations and modulate parameters to their own liking. This is all much more useful than armchair critiques, peer or not. Magic becomes a skill once you become familiar with it.

Citation: Sankararaman S, Patterson N, Li H, Pääbo S, Reich D (2012) The Date of Interbreeding between Neandertals and Modern Humans. PLoS Genet 8(10): e1002947. doi:10.1371/journal.pgen.1002947

(Republished from Discover/GNXP by permission of author or representative)
• Category: Science • Tags: Anthropology, Human Evolution, Human Genetics 
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