What did modern humans look like during the “Out of Africa” event?


Recently I was having an email exchange with a friend (a prominent public intellectual who is not a scientist), and we were thinking about what “ancestral Africans” looked like. More precisely, the populations which were resident around ~100,000 to ~200,000 years before the present. These are the people who are depicted in paleoanthropology documentaries. Here were some of my major contentions:

1) We don’t know what they looked like
2) They probably were more likely to look like modern Africans than non-Africans
3) But modern Africans are diverse in their looks and we could expect that ancient Africans were too

The neighbor-joining tree above is generated with a naive model of successive bifurcation.

1) Khoisan split off 200,000 years ago
2) Mbuti split off 150,000 years ago
3) Mende split off 100,000 years ago
4) Japanese about 50,000 years ago
5) While Pathan and Basque only 15,000 years ago

The model is wrong in the details. Pathan and Basque have some ancestry is which recently diverged, and much that is deeply diverged. The 15,000 year value is just an average. Similarly, the Khoisan have some Eurasian ancestry. But in the broad sketch it illustrates that some African populations diverged a very long time ago from other groups.

Ancient Africans date to ~200,000 years before the present for all the modern populations. Khoisan to Japanese. You could probably use phylogenetic character reconstruction methods to attempt to infer what ancient Africans looked like…but I’m not sure that it would be useful since modern humans have spread over so many ecologies over such a short span of time.

Outside of Sub-Saharan Africa perhaps on the order of 95% of the ancestry derives from an expansion from a small founder group between 60 and 80 thousand years ago. Removing the “Basal Eurasian” component, groups as diverse as Native Americans, Oceanians and East Asians probably derive their ancestry from a common group which flourished between 50 and 60 thousand years ago (this pulse is the majority of the ancestry of Europeans and South and West Asians as well).

The point here is to illustrate that 50,000 years is definitely sufficient for a great deal of diversity to have emerged in human physical variation. And yet the Khoisan are ~200,000 years diverged from their ancestors within Africa. We actually know that indigenous southern Africans have been selected for lighter pigmentation. We also know that loci associated with pigmentation in modern humans exhibits a lot of variation in Africans, and this variation is likely an ancestral feature of our species.

In sum, the number of generations between ancestral Africans and all modern descendent populations is great enough that I’m not uncertain that we can predict what they look like in anything except their skeletal features. Additionally, most of the history of anatomically modern humans was likely highly structured within Africa. That’s another way of saying that ancient Africans themselves were probably physically diverse.

With all that being said, all things equal ancient Africans probably are more likely to look like modern Africans than modern non-Africans. The main reason is simply that modern Africans occupy the same broad ecological landscape as ancient Africans, and many of our features, from our build to our complexion seem dependent upon environmental pressures. There’s lot of evidence that very light skin is probably a derived characteristic of our species (there are consistent signatures of sweeps around pigmentation loci). And, there is also evidence that some of the archaic introgression into non-Africans may have consequences in our morphology and external physical characteristics. For example, Eurasians seem to have very high frequencies of Neanderthal variants of the keratin gene. This is implicated in hair, skin and nail development.

Addendum: Note that even if we have ancient genomes, polygenic characteristics are still hard to predict. Even today common SNPs only explain a minority of the variation in hair color in Europeans.

Who We Are and How We Got Here, a book worth reading

Yesterday I talked to a friend who has a review copy of Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past. They gave me a preview (their overall assessment was positive).

I haven’t personally asked to get a copy because, to be honest, I thought there wouldn’t be anything new in it. If you “read the supplements” what more could there be in 368 pages? So I was waiting until the end of the month to buy the book and read it in my own sweet time as due diligence.

Well, this morning I asked a publicist to send me a copy. I will be getting it next week. The reason is that I’m told the latter portions of the book are quite challenging and candid as to what genetics may tell us in the 21st century. Who We Are and How We Got Here is a 21st-century revision and update of The History and Geography of Human Genes. But it’s apparently a lot more.

Also, I make a small cameo in the book, as does Eurogenes and Dienekes. I have always appreciated how the David Reich and Nick Patterson and their whole lab has taken people outside of the halls of the academy seriously. They didn’t need to as a matter of professional necessity but often engage as a matter of decency and seriousness.

Another great-great-great…great-uncle in Asia


The paper which surveys the relationship of the 40,000 year old Tianyuan sample is finally out in Current Biology, 40,000-Year-Old Individual from Asia Provides Insight into Early Population Structure in Eurasia. There isn’t anything too surprising here. Here is the part of the abstract that presents new finding:

…we generated genome-wide data from a 40,000-year-old individual from Tianyuan Cave, China…We find that he is more related to present-day and ancient Asians than he is to Europeans, but he shares more alleles with a 35,000-year-old European individual than he shares with other ancient Europeans, indicating that the separation between early Europeans and early Asians was not a single population split. We also find that the Tianyuan individual shares more alleles with some Native American groups in South America than with Native Americans elsewhere, providing further support for population substructure in Asia [8] and suggesting that this persisted from 40,000 years ago until the colonization of the Americas. Our study of the Tianyuan individual highlights the complex migration and subdivision of early human populations in Eurasia.

The Tianyuan sample lived about ~40,000 years ago in China, and it does not seem to have been the direct ancestor of modern East Eurasians. It also seems to have had some relationship to the Australo-Melanesian affiliated population which contributed ancestry to the indigenous peoples of South America. Additionally, it also shares ancestry above what you’d expect with a 35,000 year old Paleolithic European, the GoyetQ116-1 sample, which is found in an Aurignacian context.

There are some direct conclusions that one can infer from this paper. First, as known beforehand the divergence between East Eurasians and West Eurasians has to predate 40,000 years before the present since this sample already shares drift with East Eurasians far more than West Eurasians. In the paper, the authors give an interval of 40,000 to 80,000 years before the present, which seems advised. Remember that “Basal Eurasians” separated before the divergence of East and West Eurasians.

Second, “ghost” populations were common. There are at minimum two ancient Eurasian populations, represented by the Oase1 sample in Romania from 40,000 years ago, and the 45,000 year old Ust’-Ishim from Siberia, who were not closely related to any populations which left descendants today.

Third, the human “family tree” looks more like a human “family bramble.” One of the interesting points in this paper is that Tianyuan shares drift with Goyet, but does not share drift with El-Miron, which seems to be descended in large from a population like Goyet. The key here is to note that Goyet is the closest proxy to some of the ancestors of El-Miron, but it may not be the ancestor at all. So if Goyet-like populations were heterogeneous in relation to East Eurasian, then El-Miron may descend from a group which never mixed with East Eurasians.

This is clear when you read many of these ancient DNA papers closely. The Mal’ta boy was representative of a population which contributed to both Northern Europeans (via Eastern Hunter-Gatherers) and Amerindians, but the deeper results also indicated that the common contributor to these populations was not the Mal’ta population, but related to them. That is, there is no expectation that the sparse sampling of ancient DNA in many regions and epochs will find the ancestral populations, as opposed to groups related to the ancestral populations.

This is a looking-through-the-glass-darkly situation. The true pattern of population relationships of the past needed to be inferred from a finite set of individuals randomly drawn from those populations. If most of those populations left no descendants due to common and repeated local extinction events, then it may be that most of the time we’re going to have to triangulate to the “true” ancestral groups, who left descendants simply due to luck.

Finally, this should really put the nail in the coffin of the idea that we can think of ancient populations are algebraic recombinations of modern populations. Modern groups almost certainly sample only a small part of the distribution of ancient populations.

The architecture of skin color variation in Africa

Baby of hunter-gatherers in Southern Africa

Very interesting abstract at the ASHG meeting of a plenary presentation,Novel loci associated with skin pigmentation identified in African populations. This is clearly the work that one of the comments on this weblog alluded to last summer during SMBE. There I was talking about the likely introduction of the derived SLC24A5 variant to the Khoisan peoples and its positive selection in peoples in southern Africa.

Below is the abstract in full. Those who follow the literature on this see the usual suspects in relation to genes, but also new ones:

Despite the wide range of variation in skin pigmentation in Africans, little is known about its genetic basis. To investigate this question we performed a GWAS on pigmentation in 1,593 Africans from populations in Ethiopia, Tanzania, and Botswana. We identify significantly associated loci in or near SLC24A5MFSD12TMEM138…OCA2 and HERC2. Allele frequencies at these loci in global populations are strongly correlated with UV exposure. At SLC24A5 we find that a non-synonymous mutation associated with depigmentation in non-Africans was introduced into East Africa by gene flow, and subsequently rose to high frequency. At MFSD12, we identify novel variants that are strongly correlated with dark pigmentation in populations with Nilo-Saharan ancestry. Functional assays reveal that MFSD12 codes for a lysosomal protein that influences pigmentation in cultured melanocytes, zebrafish and mice. CRISPR knockouts of murine Mfsd12 display reduced pheomelanin pigmentation similar to the grizzled mouse mutant (gr/gr). Exome sequencing of gr/gr mice identified a 9 bp in-frame deletion in exon two of Mfsd12. Thus, using human GWAS data we were able to map a classic mouse pigmentation mutant. At TMEM138…we identify mutations in melanocyte-specific regulatory regions associated with expression of UV response genes. Variants associated with light pigmentation at this locus show evidence of a selective sweep in Eurasians. At OCA2 and HERC2 we identify novel variants associated with pigmentation and at OCA2, the oculocutaneous albinism II gene, we find evidence for balancing selection maintaining alleles associated with both light and dark skin pigmentation. We observe at all loci that variants associated with dark pigmentation in African populations are identical by descent in southern Asian and Australo-Melanesian populations and did not arise due to convergent evolution. Further, the alleles associated with skin pigmentation at all loci but SLC24A5 are ancient, predating the origin of modern humans. The ancestral alleles at the majority of predicted causal SNPs are associated with light skin, raising the possibility that the ancestors of modern humans could have had relatively light skin color, as is observed in the San population today. This study sheds new light on the evolutionary history of pigmentation in humans.

Much of this is not surprising. Looking at patterns of variation around pigmentation loci researchers suggested years ago that Melanesians and Africans exhibited evidence of similarity and functional constraint. That is, the dark skin alleles date back to Africa and did not deviate from their state due to selection pressures. In contrast, light skin alleles in places like eastern and western Eurasia are quite different.

Nyakim Gatwech

This abstract also confirms something I said in a comment on the same thread, that Nilotic peoples are the ones likely to have been subject to selection for dark skin in the last 10,000 years. You see above that variants on MFSD12 are correlated with dark complexion. In particular, in Nilo-Saharan groups. The model Nyakim Gatwech is of South Sudanese nationality and has a social media account famous for spotlighting her dark skin. In comparison to the Gatwech and the San Bushman child above are so different in color that I think it would be clear these two individuals come from very distinct populations.

The fascinating element of this abstract is the finding that most of the alleles which are correlated with lighter skin are very ancient and that they are the ancestral alleles more often than the derived! We’ll have to wait until the paper comes out. My assumption is that after the presentation Science will put it on their website. But until then here are some comments:

  • There is obviously a bias in the studies of pigmentation toward those which highlight European variability.
  • The theory of balancing selection makes sense to me because ancient DNA is showing OCA2 “blue eye” alleles which are not ancestral in places outside of Western Europe. And in East Asia there their own variants.
  • Lots of variance in pigmentation not accounted for in mixed populations (again, lots of the early genomic studies focused on populations which were highly diverged and had nearly fixed differences). Presumably, African research will pick a lot of this up.
  • This also should make us skeptical of the idea that Western Europeans were necessarily very dark skinned, as now we know that human pigmentation architecture is complex enough that sampling modern populations expand our understanding a great deal.
  • Finally, it’s long been assumed that at some stage early on humans were light skinned on most of their body because we had fur. When we lost our fur is when we would need to have developed dark skin. This abstract is not clear at how far long ago light and dark alleles coalesce to common ancestors.

The Tibeto-Burman and Austro-Asiatic ancestry of Bengalis

My father’s mtDNA lineage phylogeography

When I first got my father’s 23andMe results the Y and mtDNA were an interesting contrast. He, and therefore myself, carried Y lineage R1a1a, the lord of the paternal lineages. That was not that great a surprise. In the 1000 Genomes results for the Bangladeshi sample 20% of the men were direct paternal descendants of the R1a1a progenitor.

The mtDNA was a surprise. It was G1a2. This was curious to me since Bangladesh has some of the highest frequencies in the world of haplogroups M, the subhaplogroups in question being mostly restricted to South Asia. I wasn’t surprised that I was R1a1a, but I was even more confident that my maternal lineage was going to be an M, as would my father’s (my own mtDNA is U2b, not common, but not so surprising). As you can see from the map 23andMe places my father’s maternal lineage somewhere in Northeast Asia. The only information I could get about the geography was for G1a, “G1a has been found in samples from China (Daur, Hui, Kazakh, Korean, Manchu, and a sample of the general population of the city of Shenyang), Japan, Korea, Vietnam, and Siberia (Yakut).”

The biggest sample of mtDNA results from Bangladesh I could find at N = 240 does not find any G at all, let alone G1a2. So this is clearly it is a rare haplogroup in the region. But, the authors do classify 13% of the Bangladeshis as carrying an “East Eurasian” haplogroup. Haplogroup A is found among Southeast Asians and Southern China, though not among Austronesians. Haplogroup F seems to have a similar distribution, as does D, B. The other haplogroups also seem “correctly” assigned in terms of modal distribution. They are all mostly East Asian.

Looking at the Y chromosome haplogroups in the 1000 Genomes there are two of O2 and O3, and one of C3, which are clearly of Southeast Asian origin. With N =5 out of 44 samples that is ~10%. O2 is interesting because it is found at very high frequencies among the Austro-Asiatic populations in South Asia, whether it be the Khasi, or Munda groups (general O2a). O3 seems associated with Tibeto-Burman populations, and C3 with East Asia more generally.

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Africa, the churning continent

Martin Meredith’s The Fortunes of Africa glosses very quickly over one of the major reasons that the “great scramble” for the continent occurred in the late 19th century, the discovery of the usefulness of quinine as an anti-malarial agent. Perhaps because I’ve read Plagues and Peoples and The Retreat of the Elephants: An Environmental History of China, I have always been conscious of the role of disease in discouraging conquest and migration (malaria in Italy was also a way to limit the extent of long-term occupation).

The coastal regions of Africa had been subject to the trade and depredations of European actors for nearly 400 years when the Berlin Conference partitioned the continent amongst European powers. Despite the fact that much of the interior was not charted, there had long been a colonial presence. Accra, the modern capital of Ghana, was originally a 16th-century Portuguese fort, but for several centuries between the 17th and 19th centuries, it was actually a possession of Scandinavian powers, Sweden and Denmark! (before passing on to the British)

For all these centuries the heart of Africa was unknown to Europeans, in part because there were native powers blocking their way, but also because the mortality rates were so high for outsiders, as indicated above. It is no surprise that the main European settlement in Africa which was more than a simple trading fort was at the southern tip of the continent, where the climate was Mediterranean and so the disease burden low.

But once quinine, and machine guns, came into the equation the interior was accessible. It all happened rather quickly in a few decades, though in some cases European ‘colonialism’ involved little more than nominal allegiance of tribal chieftains.

Now, a new paper in Cell may herald the beginning of a great genomic scramble to understand the history of Africa. Carl Zimmer in The New York Times has a piece up, Clues to Africa’s Mysterious Past Found in Ancient Skeletons. It begins:

It was only two years ago that researchers found the first ancient human genome in Africa: a skeleton in a cave in Ethiopia yielded DNA that turned out to be 4,500 years old.

On Thursday, an international team of scientists reported that they had recovered far older genes from bone fragments in Malawi dating back 8,100 years. The researchers also retrieved DNA from 15 other ancient people in eastern and southern Africa, and compared the genes to those of living Africans.

The general results of the paper, Skoglund et.al’s Reconstructing Prehistoric African Population Structure, were presented at the SMBE meeting this summer. So in broad sketches I was not surprised, though the details require some digging into.

The Bantu Expansion repatterned the population structure of Africa

Between 1000 BC and 500 AD the expansion of iron wielding agriculturalists from the environs of modern day southern Cameroon reshaped the cultural and genetic landscape of Sub-Saharan Africa. The relatively late date of this expansion should give us a general sense of how careful we need to be about making assertions about “prehistoric Africa.” When Egypt’s New Kingdom was expanding southward along the Nile and into the Levant, Sub-Saharan Africa was qualitatively very different from what we see today in both culture and genetic structure. The continent’s contemporary human geography does not have a deep time depth.

In any case, anyone who has worked with genetic data from Africa is struck by how similar Bantu-speaking populations are genetically. So these results are not world-shaking. South African Zulus occupy positions far closer to Kenyans and Congolese than they do to Khoisan peoples to the west of them facing the Kalahari. The Xhosa people on the cultural frontier of the Bantus in South Africa exhibit substantial admixture from Khoisan (to the point where they have even integrated clicks into their language!), but even they are preponderantly non-Khoisan.

By sampling ancient genomes across a geographical transect which runs up the Rift Valley to Ethiopia, Skoglund et al. show that before the Bantu Expansion there was a north-south genetic relatedness cline. When this result was presented at SMBE a few friends were quite excited that they were being presented a cline, as some researchers have felt that this particular lab group has a tendency to model everything as pulse admixtures between distinct ancestral populations. But the reasonably deep time transect in Malawi exhibited no variance in admixture fractions, which is indicative of the likelihood that its “mixed” status at a particular K cluster is simply an artifact (see this post for what’s going on).

One particular aspect of the results from Malawi is that they found no continuity between contemporary populations, Bantu agriculturalists, and these ancient hunter-gatherers. That is, hunter-gatherers were replaced in toto. This is not entirely surprising, as many researchers who have worked with European ancient DNA believe that hunter-gatherers in many areas left no descendants at all as well (the “hunter-gatherer” fractions in modern groups in a particular region are believed to be due to migration of mixed populations who obtained “hunter-gatherer” ancestry at another locale).

But the Bantus were not the first “intrusive” population

These results also have some moderate surprises. A Tanzanian sample from 1100 BC from a pastoralist context exhibits an ancestral mix which is Sub-Saharan African and West Eurasian/North African. More precisely, about 38 percent of this individual’s ancestry resembles that of the Pre-Pottery Neolithic culture of the Levant, and the rest of the genome most resembles a 4500 year old sample from Ethiopia.

This date is before the initiation of the Bantu Expansion. The genetic results in this work, and earlier publications, strongly points to the likelihood that this population(s) mediated the spread of pastoralism to the south and west. In particular, all Khoisan groups of southern Africa seem to have admixture from this group, more (Khoi) or less (San).

But a curious aspect of this result is that these early pastoralists do not carry any evidence of admixture from ancient eastern farmers from the Zagros region. That is, the West Eurasian gene flow into the Tanzanian pastoralists predates the great exchange/admixture in the Middle East between western and eastern lineages. Since that reciprocal gene flow seems to have occurred at least 2,000 years before the Tanzanian pastoralist’s time, it suggests that this West Eurasian element was in Africa for thousands of years.

The second important point to emphasize is that the Iranian-like component is found among Cushitic speaking Somali and Afar samples, at 15-20% clips. Looking at the supporting tables a wide range of East African populations have the Tanzanian pastoralist ancestry but do not show evidence of the Iranian-like ancestry, which is now ubiquitous in the Middle East, and presumably in the highlands of Ethiopia as well (which usually show somewhat higher levels of Eurasian ancestry than is the case on the coast, especially among Semitic language speakers).

This fact is important because many of the Nilotic peoples are reputed to have absorbed Cushitic groups relatively recently in the past. This is also true for Bantu speaking groups according to these and other data. Finally, the Sandawe, who speak a language with clicks, and so may have some affinity to Khoisan, are often stated to have Cushitic affinities (looking at the data they clearly have West Eurasian ancestry). But their Eurasian ancestry seems to lack the Iranian-like component as well.

None of the populations with putative Cushitic ancestry, but who lack Iranian-like ancestry, speak a Cushitic language (most speak Nilotic languages, but East African Bantus have mixed with these Nilotic groups, so they have the same ancestry). Therefore I wonder if these pastoralists spoke an Afro-Asiatic language in the first place.

A patchy landscape

The phylogenetic tree illustrates the relationships of various African populations without much recent Eurasian ancestry. In The New York Times article David Reich indicates that the Hadza people of Tanzania are the closest Sub-Saharan Africans to the lineage ancestral to non-Africans. This is actually a simplification of what you see in the paper, and is illustrated in the tree to the left. The 4500 year old Ethiopian sample, which does not have Eurasian ancestry, nevertheless is the closest of all Sub-Saharan groups to Eurasians. The Hadza have the highest fraction of this ancestral component of all Sub-Saharan Africans in their data set, but many other populations also carry this ancestry (the Tanzanian pastoralist combined the PPN ancestry with this element).

This was a patchy landscape of inhabitation, because though the Tanzanian pastoralist ancestry, a combination of PPN and proto-Ethiopian, spread all the way to the Cape, there were populations, such as the Hadza and a 400 year old individual sampled from the Kenya island of Pemba, which lacked this genetic variation. Indeed, they are also not on the north-south (proto-Ethiopian to Khoisan) cline that featured so prominently above.

The sampling of ancient individuals is not very dense yet, so we can’t say much. But I think it does indicate we need to be cautious about assumpting gene flow dynamics as-the-crow-flies, simply a function of distance. Ecological suitability no doubt plays a strong role in how populations expand. The Bantus, for example, were stopped in South Africa by the fact that their agricultural toolkit was not suitable for the western half of the country. So when Europeans arrived in the 16th century the residents of the Cape where Khoi pastoralists.

The presence of the Hadza in Tanzania, or an individual of unmixed proto-Ethiopian ancestry on Pemba 400 years ago, indicates that the ethnic geography of East Africa has long been fluid and dynamic. There is no reason to suppose that the Hadza are not themselves migrants from further north, perhaps easily explaining why they are not on the north-south cline so evident from the ancient DNA.

The rise of Basal Humans

Several years ago researchers discovered that the first farmers of Europe, who descended from an Anatolian population, were in part derived from a group which split off very early from other Eurasian populations. This group was termed “Basal Eurasian” (BEu) because it was an outgroup to all other Eurasians, including European hunter-gatherers, East Asians, Oceanians, and the natives of the New World. Subsequent work has shown that the early Neolithic farmers of the Near East, whether they’re from the Levant or the Zagros, had about half their ancestry from this population.

No ancient genomes which are predominantly BEu have been discovered yet. The fact that populations on the cusp of the Holocene seem to have Basal Eurasian ancestry across the Middle East suggests that the admixture with hunter-gatherers related to those of Europe must have occurred during the Pleistocene. But Basal Eurasian is arguably the most parsimonious explanation of the shared drift patterns that we see.

Skoglund et al. suggest that there may be the necessity of a similar construct in Africa. They are not the first, Schlebusch et al. also suggested the necessity of this lineage in the supplements of their preprint on ancient South Africans. Within Skoglund et al. the authors see variation between the far West African Mende and the eastern West African Yoruba, where the latter exhibits closer affinity to East African populations than the former (this includes those such as the proto-Ethiopian with no Eurasian admixture). Additionally, the authors found that Khoisan groups share more alleles with populations in East Africa than they do with those in West Africa even when you account for admixture.

One model that can explain this variation is long range gene flow, so that there would be connections between various regions as a function of their distance. Another explanation is that West African populations are the product of a Basal Human (BHu) population which separated first, before the bifurcation of Khoisan from other human populations. This would reorder our understanding of who the most basal humans are. Additionally, it would align with long-standing work on deep lineages within Africa contributing a minor component of the continent’s ancestry.

As should be clear due to the tree above, BHu postdates the separation of African humans from Neanderthals. One does wonder about the relevance of the Moroccan “modern” human to these models.

Understanding culture from genetics and genetics from culture

The spread of the Bantus over 1500 years from one end of the continent to the other is perhaps one of the most important dynamics we can use to understand the spread of farming more generally. The linguistic unity of the Bantus, or at least their affinity, suggests to us that the first farmers of Europe, who spread across much of the continent in 2500 years, probably exhibited the same pattern. The low levels of gene flow between hunter-gatherers and farmers, despite living in the same regions for thousands of years, can be illustrated with African examples (e.g., the Hadza vs. their Bantu neighbors).

We are rather in the early phase of understanding these dynamics. There are more remains to be found, perhaps in the dry fastness of the Sahara or Sahel? (though unfortunately political considerations may prevent excavation due to danger to archaeologists) The genetics will give us a general idea about the nature of genetic variation and how it arose, but robust cultural models also need to be developed which illustrate how these genetic patterns arose.

Citation: Reconstructing Prehistoric African Population Structure, Skoglund, Pontus et al. Cell , Volume 171 , Issue 1 , 59 – 71.e21

Population structure in Neanderthals leads to genetic homogeneity


The above tweet is in response to a article which reports on the finding past month in PNAS, Early history of Neanderthals and Denisovans. It’s open access, you should read it. I don’t think I’ve reviewed it because I haven’t dug through the supplements. To be frank this is a paper where you pretty much have to read the supplements because they’re introducing a somewhat different model here than is the norm.

I talked to Alan Rogers at SMBE about this paper. Broadly, I think there might be something to it, and it’s because of what David says above. It is simply hard to imagine that Neanderthals could be extremely successful with such low genetic diversity as we see, and spread so thin. Now, the Quanta Magazine tries to emphasize that the effective population is not the true census population, but I wish it would have explained it more clearly. Basically, the size that is relevant for breeding is obviously not going to the same as a head count. And, because effective populations are highly sensitive to bottlenecks you can get really small numbers even when the extant population at any given time may be large.

The PNAS paper makes some novel inferences, and I’ll set that to the side until I read the supplements. But I don’t think it’s crazy that population structure within Neanderthals could be leading to lower total genetic diversity.

Release the UK Biobank! (the prediction of height edition)


There’s so much science coming out of the UK Biobank it’s not even funny. It’s like getting the palantír or something.

Anyway, a preprint, submitted for your approval. A vision of things to come? Accurate Genomic Prediction Of Human Height:

We construct genomic predictors for heritable and extremely complex human quantitative traits (height, heel bone density, and educational attainment) using modern methods in high dimensional statistics (i.e., machine learning). Replication tests show that these predictors capture, respectively, ~40, 20, and 9 percent of total variance for the three traits. For example, predicted heights correlate ~0.65 with actual height; actual heights of most individuals in validation samples are within a few cm of the prediction. The variance captured for height is comparable to the estimated SNP heritability from GCTA (GREML) analysis, and seems to be close to its asymptotic value (i.e., as sample size goes to infinity), suggesting that we have captured most of the heritability for the SNPs used. Thus, our results resolve the common SNP portion of the “missing heritability” problem – i.e., the gap between prediction R-squared and SNP heritability. The ~20k activated SNPs in our height predictor reveal the genetic architecture of human height, at least for common SNPs. Our primary dataset is the UK Biobank cohort, comprised of almost 500k individual genotypes with multiple phenotypes. We also use other datasets and SNPs found in earlier GWAS for out-of-sample validation of our results.

A scatter-plot is worth a thousand derivations.

You know what better than 500,000 samples? One billion samples! A nerd can dream….

Massive genomic sample sizes = detecting evolution in real time

The recent PLOS BIOLOGY paper, Identifying genetic variants that affect viability in large cohorts, seems to have triggered a feeding frenzy in the media. For example, Big Think has put up Researchers Find Evidence That Human Evolution Is Still Actively Happening.

I wasn’t paying close attention because of course human evolution is still happening actively. From a genetic perspective, evolution is just change in allele frequencies. Populations aren’t infinite, so even if there wasn’t any selection stochastic forces would shift allele frequencies. But of course selection is probably happening. For adaptation by natural selection to occur you need heritable variation on a trait where there are fitness differences as a function of variation within the population. It seems implausible that these conditions don’t still apply. There’s plenty of fitness variation in the population, and it’s unlikely to be random as a function of heritable variation.

But the devil is in the details. And last year Field et al. used the modern genomic tools available to detect selection occurring over the past 2,000 years. It is not credible that it would have magically stopped a few centuries ago.

So why is this new paper such a big deal? (note that it’s in PLOS BIOLOGY, not PLOS GENETICS) Because the method they use is ingenious and simple. Basically, they’re looking at changes in allele frequencies as a function of age in huge populations. It’s a little more complicated than that, they used a logistic regression to control for some of the other variables. But they found some biologically plausible hits with their data set of 50,000-150,000. And, they replicated their hits from a European sample to a non-European one.

This does bring me back to a discussion I observed a while back. An evolutionary geneticist who works with Drosophila mentioned offhand that in his field there really wasn’t that much of a need for more data. They could spend all their time to doing analysis. A prominent human geneticist whose work focused on biomedicine piped up that that wasn’t true at all for their field. There are some differences in the scientific questions, but there are also differences in terms of what you can do with humans as a model organism.

In the paper they look forward to the day of increasing sample sizes an order of magnitude beyond where it is now. At some point in the near future, large fractions of entire nations will be sequenced at medical grade level (30x coverage).

Anyway, you should read Identifying genetic variants that affect viability in large cohorts. It’s pretty straightforward.