We’re descended from Lilith and Eve

From the comments:

Something that confused me very early on in the book- the San are shown branching off from the rest of humanity prior to Mitochondrial Eve. How can Eve be a common ancestor in this case? Admixture?

The commenter is talking about an early portion of Who We Are and How We Got Here. Someone who reads a book like that is “in the know,” and this is a reasonable question. But it points to a bigger issue that’s going to crop up with the complexificaiton of the origin of anatomically modern humanity over the last few years, and proceeding forward.

An upside of the very-recent-out-of-Africa model, where all modern humans descended exclusively from a group of East Africans who lived ~50,000 years ago, is that it was very simple. So simple that you could write the model out on a postcard.

The new model benefits from being correct and making humans less sui generis (though perhaps that is a bug rather than a feature to some?), but it also forces more thought and complexity on the lay audience.

Calibration on the coalescence of the last common ancestor of all mitochondrial DNA lineages for humans has changed several times, the last estimates are for a time to last common ancestor for all mtDNA lineages being around 100 to 200 thousand years ago. This is curious in light of the fact that both fossils and genomics are starting to suggest that anatomically modern humans emerged in their current form 200 to 400 thousand years ago.

The shallower coalescence isn’t that surprising. Y and mtDNA both have lower effective population sizes and so higher turnover rates. These high turnover rates mean the extinction of other lineages. As most of you know, the extinction of these mtDNA lineages does not mean that the genetic material of other women alive at the same time as “mtDNA Eve” is not present in modern humans (though who knows what it means to say there’s distinctive genetic material left after all these generations with recombination). Eve was always simply a personification of the coalescence of the mtDNA genealogy. Both the Y and mtDNA phylogenies and coalescence were useful in their time. They pointed to the likely important role of Africa in the origin of modern humans, and the relatively recent time depth of our species. But their coalescence at a specific time was somewhat random around a certain expected value. This is why it was not surprising at all that “Y chromosomal Adam” and “mtDNA Eve” lived at different times (there is some evidence that the Y chromosome has had a lower long-term effective population size).

The above question is inspired by the fact that San Bushmen seem to diverge earlier in their total genome than in their mtDNA. There’s always been a distinction in the literature between demographic divergence between two populations, and the divergence of their genetic genealogies. Oftentimes daughter populations share genetic variation that dates back to before their separation. But sometimes, you have this situation where it seems that the starting point of genetic variation post-dates the divergence between population.

What’s the explanation? I think the simplest one is admixture and reciprocal gene flow, as implied by the commenter. In fact, Pontus Skoglund’s latest African ancient DNA paper implies that there was some sort of isolation-by-distance cline in the eastern part of the continent, from modern Ethiopia far to the south.

And, it may also turn out that the San Bushmen themselves are an admixture between two very different populations, one more like other eastern Africans, and one basal to this clade. If so, then it may be that their divergence estimate is a compound, and the most divergent mtDNA lineages come from the eastern African population that mixed with the more basal population.

The bigger answer is that we really need to move beyond the “mitochondrial Eve” story as being central. It had its time and played its role, but we can move beyond it. Otherwise, the public will be in for a big surprise as ancient DNA starts to uncover the story of a whole antediluvian world within Africa of anatomically modern humans that flourished for hundreds of thousands of years before a small branch left to populate the rest of the world ~50,000 years ago.

On the eons of salutary neglect

New preprint, Something old, something borrowed: Admixture and adaptation in human evolution. This part jumped out at me:

…Indeed, for most traits, the contribution of archaic human alleles to present-day human phenotypic variation is not significantly larger than those of randomly drawn non-introgressed alleles occurring at the same frequency in modern humans. Interestingly, in both studies, neurological and behavioral phenotypes are an exception, with Neanderthal alleles contributing more to variation in these traits than frequency-matched modern human alleles.

I joked that perhaps we can talk about people “acting like a Neanderthal” again?

But seriously, I was thinking today about one particular stage of human evolutionary history, the long sojourn outside of Africa for the ancestors of non-Africans (including “Basal Eurasians”) which produced a sustained bottleneck. In David Reich’s new book he alludes to it, and I’ve seen other mentions of it (this is an old idea).

How long was the bottleneck? What was the normal census size? What were the cultural implications of having a small isolated population?

The PSMC and MSMC diagrams I’ve seen don’t really answer my questions.

Carl Zimmer profile of the Reich group at work

The New York Times has a review up (sort of) of Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past, David Reich Unearths Human History Etched in Bone. But since Carl has been covering the publications coming out of the Reich lab for many years now it’s kinds of a survey of the whole operation and how David and company go where they are.

The last few paragraphs are pretty tantalizing:

As of last month, Dr. Reich’s team has published about three-quarters of all the genome-wide data from ancient human remains in the scientific literature. But the scientists are only getting started.

They also have retrieved DNA from about 3,000 more samples. And the lab refrigerators are filled with bones from 2,000 more denizens of prehistory.

Dr. Reich’s plan is to find ancient DNA from every culture known to archaeology everywhere in the world. Ultimately, he hopes to build a genetic atlas of humanity over the past 50,000 years.

“I try not to think about it all at once, because it’s so overwhelming,” he said.

Three years ago I was having a discussion with someone from Reich’s group and mentioned offhand that in terms of getting data I give the nod to Eske Willerslev’s group of researchers, though I thought the people around David and Nick Patterson tended to perform a deeper analysis. Three years is a long time, and as the results since then have shown, the “SNP capture” methodology is very cost effective. They might not get the whole genome sequences of individuals, but they get lots of individuals. And for a lot of population genomic analysis, you want lots of individuals more than the whole genome sequence.

But not all. The more ancient individuals probably have a lot of variation “private” to them and their population, so you don’t know all the neat polymorphisms you might miss.

With that gripe submitted, it’s pretty incredible that the Reich lab has 3,000 ancient samples in the pipeline for analysis. In Who We Are and How We Got Here David Reich outlines just how he and his collaborators transformed the artisanal process of data generation from ancient DNA into a rationalized and commoditized factory process.

White modern Northern Europeans are genetically more like brown South Asians than brown(ish) ancient Northern Europeans were

The Guardian has a piece by Arathi Prasad, Thanks to Cheddar Man, I feel more comfortable as a brown Briton. Dr. Prasad is a geneticist, so the science is pretty decent (she’s probably seen the documentary ahead of time too).

But there is a curious quirk here and it reveals something about human psychology: modern Britons are genetically much closer to South Asians, like Arathi Prasad, than these ancient darker-skinned Britons. The plot to the left illustrates this (it’s using the Dystruct package). The far right of the top panels represent South Asians. You can see Europeans pretty clearly. Let’s note two things:

1) Modern Europeans (except for Sardinians) share an orange “steppe” component with most South Asians (these are no doubt Indo-European migrations of the Bronze Age)

2) The brown element represents European hunter-gatherers. This element is found at varying quantities across Europe, with the lowest fractions in Sardinians. Though present in South Asians (this may or may not be an artifact to be honest), it’s not present at very high frequencies.

One always has to be careful about taking these proportions as literal representations of ancestral populations. They are not. But what they show is that modern Northern Europeans and South Asians have been touched by the same population movements over the past 5,000 years, and so are genetically much closer than the people who lived in Northern Europe and South Asia 5,000 years ago.

Humans are a visual species. In a pre-modern environment, physical cues were important for group identity, though I suspect just as much due to scarification and tattooing as phenotypic differences due to biology. The fact that Cheddar Man, and Paleolithic hunter-gatherers in Western Europe more generally, probably resembled modern South Asians more than they do modern Northern Europeans (I think they were more likely to be olive-brown than dark-brown, but I’m not confident), is more salient to human folk biology than the fact that modern Northern Europeans are much closer genetically to South Asians than the more “brown” ancient Northern Europeans.

Stuff like this always reminds me of the deep wisdom in Artur C. Clarke’s Childhood’s End. The ultimately benevolent alien species which mentored humanity shielded us from their physical appearance because the knew we’d find it horrifying. The substance of what they did for us, who they were, was going to be less important to immature humans than the fact of what they looked like.

Note: Fst between Sindhi from Pakistan and WHG (Cheddar Man was one) is 0.087. Sindhi from Pakistan and English is 0.023. English to WHG is 0.058 (source). Fst can not be naively interpreted as “genetic distance.” But, this gets at the fact that Mesolithic European hunter-gatherers were very distant from modern South Asians. And widespread gene flow and admixture over the past 5,000 has compressed a lot of genetic differences which were starker across geography in the past.

Ancient DNA and Dystruct

There’s a new preprint, Inference of population structure from ancient DNA, which uses explicit demographic models to make inferences about ancestry. I haven’t dug into the guts of the math, but, the outputs are quite interesting.

What seems to be obvious is that Western Eurasia has a much richer set of models to choose from than elsewhere. European, Middle Eastern and South Asian populations exhibit the greatest difference between Dystruct and Admixture.

Five things paleogenetics tells us about the human past

Since I’m flogging Enlightenment Now, I thought perhaps I should remind readers that Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past by David Reich is out in 1.5 months. For years people have asked me about a book to read to understand what genetics has to say about human history. This is that book.

And yet before you get there, what do you need to know?

Here are five things you should know. Five things that we know with a very high degree of certitude.

  1. Many (most?) modern populations clusters we perceive as clear and distinct date to the last 5,000 years. To give a concrete example, the genetics that we find to be typical of Northern Europeans only comes into being ~5,000 years ago, with the Corded Ware populations. To my knowledge none of the prior populations along the North European plain exhibit the mix of characteristics and ancestries typical of modern Northern Europeans in any way, shape, or form.
  2. Concomitantly, many of the physical characteristics we find typical of modern populations are probably relatively recent configurations due to natural selection.
  3. Non-African populations, whether European, Middle Eastern, South Asian, (South)East Asian, Amerindian or Oceanian, derive from a population expansion that dates to ~50,000 years BP. These populations experienced a bottleneck on the order of 1,000 to 10,000 breeding individuals.
  4. Modern humans are old. Population structure within Africa of modern humans dates to at least 200,000 years before the present, and perhaps even earlier.
  5. Population turnover was ubiquitous. Change was the only constant.

Neanderthal introgression in the ancient DNA age

Over the past ten years or so the idea of “adaptive introgression” in the human context has gone from seeming ludicrous to banal. When I first began entertaining this idea in 2006 some commenters literally heckled me, because the idea of admixture with Neanderthals seemed so ludicrous. Then, in 2010 the maturation of the field of ancient human DNA confirmed that it was likely non-Africans had Neanderthal admixture. Over the next few years, specific instances of introgression were discovered (e.g., EPAS1 from a Denisova-relative).

Today the whole landscape of adaptive introgression from other lineages is now being mapped. An open access paper in Molecular Biology and Evolution, Disentangling Immediate Adaptive Introgression from Selection on Standing Introgressed Variation in Humans, examines the distinction between the immediate sweep of an introgressed allele after admixture, and later selection on alleles which are segregating neutrally within the absorbing population.

The authors developed a statistic which detected “immediate adaptive introgression (iAI).” Instances where alleles increased in frequency immediately after the admixture in the modern human background from Neanderthals (or possibly other archaics?).

One interesting gene was LYPD6B. This seems to have been subject to selection immediately, and it’s widely distributed in modern non-Africans. This locus controls “cholinergic signaling in the brain” and the authors suggest that the “results suggest that selection on this introgressed haplotype may have been due to beneficial behavioral and/or physiological traits.” The other possible cases of iAI seem mostly involved immune response, not entirely surprising.

But perhaps the bigger issue is that there may be a lot of selection on segregating variants that came in from Neanderthals. That is, introgression may be more important for selection on standing variation. This is is probably the dominant mode of adaptation in humans in any case. Think of it is portfolio diversification.

Speaking of variation, there’s a paper in the works which suggests that admixture with Neanderthals replenished some of the genetic diversity that the Out-of-Africa modern lineage lost:

“They left many beneficial variants behind in Africa,” says evolutionary genomicist Tony Capra of Vanderbilt University in Nashville, who reported the results. “Interbreeding with Neandertals provided an opportunity to get back some of those variants, albeit with many potentially weakly deleterious Neandertal alleles as well.”

Why the Chinese don’t buy deodorant

In human populations a SNP in ABCC11 is correlated with two salient traits: 1) wet or dry earwax 2) body odor. When I had my first son sequenced before his birth the main variant of phenotypic consequence that I noticed (aside from him being a heterozygote on KITLG), was that he carried a derived mutation on this position. Meaning that he was going to have dry earwax and fewer issues with body odor.

My wife and I are both heterozygotes. This is not too surprising. The derived variant is actually greater than 50% in Bengalis in the 1000 Genomes (in South India the derived variant is also around ~50%), while about ~25% of Northern Europeans are heterozygotes.

This genetic story came to my mind again because of this article in The New York Times, Aiming at China’s Armpits: When Foreign Brands Misfire:

There’s another reason few Chinese consumers buy deodorant: basic biology.

Scientists in recent years have shown that many East Asians, a group that includes China’s ethnic Han majority, have a gene that lowers the likelihood of a strong “human axillary odor” — scientist-speak for body stink.

That lowers the likelihood that they will use deodorant to begin with, according to a 2013 study by researchers at the University of Bristol and Brunel University in Britain, after a survey of nearly 6,500 women of various backgrounds.

“It is likely that deodorant usage is not widely adopted because there is, for much of the East Asia population, no need for it,” it said. (For those curious about such matters, that same genetic difference also leads to drier earwax.)

A friend of mine in undergrad of East Asian background told me once that she had never worn deodorant. So this shouldn’t be very surprising.

Today I found a paper, A missense variant of the ABCC11 gene is associated with Axillary Osmidrosis susceptibility and clinical phenotypes in the Chinese Han Population, which explicitly probes the correlation between body odor (“Axillary Osmidrosis”) and the SNP in question in the Han Chinese population.

The chart below makes the association obvious:

The correlation between carrying the G, ancestral, allele, and body odor is very strong. Though it is imperfect. Going through this literature human smells are clearly a polygenic trait (see The effect of ethnicity on human axillary odorant production). That being said, this case-control study in a Han population shows ABCC11‘s importance in at least East Asian populations (earlier work in Japan showed that those with body odor tended to have wet earwax and carry the G allele as well).

In regards to the genotype proportions the authors observe:

The excessive heterozygosity observed in AO individuals is probably due to the effect of selection, particularly nonrandom mating against AO phenotype.

This doesn’t make sense to me. Wouldn’t people who have body odor tend to pair up in a society where they are a minority? The authors note that the excess of heterozygotes was observed in earlier studies too.

If you dig into the frequencies it seems that the derived mutation is absent among populations in Africa without recent Eurasian back-migration. I looked it up, and it’s segregating in ancient Eurasian samples, with Ust Ishim being a heterozygote. It is curious that in no population has the derived frequency swept to fixation, nor has the ancestral variant fixed in other groups (such as in Europe).

I strongly doubt that there is any selection on this locus due to earwax or body odor. It is a pleiotropic locus, there are other effects from the mutation. One of those other effects is probably the target of any selection. And in regards to selection, it seems likely that that would be a balancing sort since neither the ancestral nor the derived variant are fixed in most populations.