July 21, 2012

Admixture matters

Until recently, tree models dominated models of human demography. Under such models, populations split off from each other in a branching pattern. African populations, and especially African hunter-gatherers, which are the most divergent occupy the basal positions in the tree. The story has been repeated many times: Africans are more genetically diverse, Eurasians carry a subset of African genetic variation, a small subset of Africans left the continent and colonized the world after going through a severe bottleneck and so on.

It's a simple and attractive story, but one which is wholly dependent on ignoring admixture. There are two types of admixture that are pertinent: one is admixture between modern human groups. An example of this is Ethiopia. Many studies have presumed to identify a signal of Out-of-East Africa based on diminishing distance from East Africa. But it is completely unclear how this model fares when one takes into account that East Africans are a recently admixed population: their great genetic diversity may be due to the recent intermingling of two very divergent groups of people (Caucasoids and aboriginal East Africans).

Or, consider two Englishmen, one with a Nigerian and another with a Chinese grandparent. These two individuals might appear greatly diverged from each other genetically and phenotypically, but this is the aggregate of sharing 3/4 of quite recent common ancestry (from their English grandparents), and not sharing 1/4 each of highly divergent ancestry (from their Chinese and Nigerian ones).

The situation is more interesting when we realize that admixture can occur not only between modern human groups, but also between modern humans and archaic ones. Both archaic genomes published so far (Neandertal and Denisova) show differential affiliation to modern human groups, and indirect evidence suggests that some African groups also admixed with archaic species that once lived in Africa.

Of course, levels of archaic admixture inferred from these studies are usually small, but we must remember that a little archaic goes a long wayThis is due to the fact that modern humans and archaic ones diverged from each other a long time ago. Their admixture, even in highly favorable (for modern humans) proportions introduces a substantial amount of new genetic variation. As a result, populations harboring archaic admixture appear more divergent from each other.

This point is made quite well in a new article:
If human populations do not all have the same level of archaic introgression, the current genetic structure of human populations might be partly shaped by differential admixture. Estimates of population sizes and divergence times between human populations should thus be affected by past admixture events. The divergence time between an admixed and a non-admixed population should be overestimated if admixture is not properly modelled. Similarly, the effective size of admixed populations should be overestimated as archaic lineages inflate genetic diversity. In Figure 2, we report a simulation study of this bias in a very simple case of population divergence without migration. The overestimations of divergence time and admixed population size are almost linearly increasing with admixture rate (Figure 2). For instance, a divergence time of 1,600 generations (40,000 y assuming a 25-y generation time) is perfectly recovered if none of the populations is admixed, but is overestimated by 100 generations (2,500 y) with 1% admixture in one population, and already by 350 generations (8,750 y) with 5% admixture. Even though our simulated scenario is unrealistically simple, it is likely that differential admixture should affect population genetic affinities under more complex models of population differentiation. The proper interpretation of human genetic affinities should thus probably be re-evaluated in the light of these results. In particular, the divergence between Africans and Oceanians (showing up to 5% archaic admixture [16]) could be more recent than previously reported (62–75 Kya [24]). It remains unclear whether the method used by Rasmussen et al. [24] to date this divergence is also sensitive to differential introgression, but, if that was the case, the colonization wave to Oceania thought to well predate that towards East Asia [24] could have occurred at roughly the same time once differential admixture had been taken into account.
This is an important point: the inferred early dispersal of Oceanians could in fact be the result of archaic admixture in both Africans and Oceanians. 


Lower levels of archaic admixture are sufficient to make two individuals or populations appear much more distant from each other. Archaic Homo populations may be as much as an order of magnitude more divergent to H. sapiens that particular H. sapiens groups are to each other.

But, admixture can also deflate divergence, if there is subsequent gene flow between the diverged populations. As an example, Near Eastern Arab populations: have both diverged from Europeans due to receiving African admixture, and also converged with them by the fact that Europeans have Neolithic Near Eastern admixture which renewed bonds between Europe and the Near East. It means little to speak of "when" Europeans and Near Eastern people diverged from each other: it's a balancing act of centrifugal and centripetal influences: if a Crusader lands on the Levant and marries a local woman, he diminishes apparent Europe-Near East genetic divergence; if a Somali does the same, he increases it. So, in the end, the apparent "divergence" between Europe and the Near East may have little to do with how much time has transpired since the colonization of a new region, and more to do with "who had sex with whom" in the intervening period.

In fact, the ability of admixture to "converge" populations is the basis of the multi-regional evolution theory, although that is usually posited in terms of gene flow. But, the basic idea is still the same: our relatively uniform human species may not be entirely the result of tree-like divergence of populations from an original African population, but rather of a confluence of streams of ancestry derived from Lower and Middle Paleolithic populations of Homo.

Admixture may not only lead us to overestimate divergence between populations: it might lead us to wrongly estimate the directionality of migration itself. 

Consider a future geneticist, working thousands of years after a collapse of civilization in the near future which led into a breakdown of long-distance travel. Such a scientist would perhaps conclude that the highest genetic diversity is to be found in North America, and conclude that North America colonized the rest of the world.

In some cases, it can well be argued that serial founder effects/bottlenecks restrict genetic variation/effective size. For example, the colonization of the Americas in three waves created a population that is clearly a subset of the East Eurasian parental population. But, notice that researchers trying to understand it had to carefully disentangle the various migration waves and cleanse their data from recent European admixture. The directionality of migration can be recovered through a diligent treatment of the evidence.

But, let's forget about the nested-subset analogy: the fact that a population X may appear to be a subset of another Y does not indicate that Y founded X any more than the fact that the genetic variation of any single European country is a subset of the cosmopolitan populations of the Americas will indicate an America-to-Europe migration to the future geneticist. Sometimes, X is a subset of Y because Y has a superset of variation formed by union with a divergent other population.

Sub-Saharan Africa is one example of a terra incognita for the historian. In the absence of written sources, science is mostly clueless as to what was going on there for thousands of years after the invention of writing in Mesopotamia. In some areas, due to the moist climate/abundant vegetation/political instability even archaeological evidence is lacking. What this means is that we are in the dark about what admixtures were going in the Dark Continent. Thankfully, people are working on it.

My own position is that while an origin of anatomically modern humans in Africa still seems to be correct, the pattern of divergence and reduced effective size of Eurasians from Africans is not wholly due to a small group of them leaving the continent at some Middle Pleistocene epoch.

How much of the African divergence and higher African effective population size is due to a Biblical-level bottlenecks coinciding with Out-of-Africa? As readers of the blog know, I don't buy the recent Out-of-Africa model, especially in its "endangered but crafty tribe of pioneers following the coast 60,000 years ago" variety. Archaic admixtures in Eurasia and Africa inflate divergence times; back-migration may deflate them. It's yet another balancing act.

Hopefully statisticians, with a little help from archaeology and palaeoanthropology can untangle the palimpsest of events and present us with a believable story about our own origins. It's time to give up trees and embrace networks!


PLoS Genet 8(7): e1002837. doi:10.1371/journal.pgen.1002837

Genomic Data Reveal a Complex Making of Humans

Isabel Alves et al.

In the last few years, two paradigms underlying human evolution have crumbled. Modern humans have not totally replaced previous hominins without any admixture, and the expected signatures of adaptations to new environments are surprisingly lacking at the genomic level. Here we review current evidence about archaic admixture and lack of strong selective sweeps in humans. We underline the need to properly model differential admixture in various populations to correctly reconstruct past demography. We also stress the importance of taking into account the spatial dimension of human evolution, which proceeded by a series of range expansions that could have promoted both the introgression of archaic genes and background selection.

Link

13 comments:

terryt said...

"In fact, the ability of admixture to 'converge' populations is the basis of the multi-regional evolution theory, although that is usually posited in terms of gene flow. But, the basic idea is still the same: our relatively uniform human species may not be entirely the result of tree-like divergence of populations from an original African population, but rather of a confluence of streams of ancestry derived from Lower and Middle Paleolithic populations of Homo".

Exactly the point I have been trying to make all along. The 'single origin' of any species has never made any sense to me at all.

"My own position is that while an origin of anatomically modern humans in Africa still seems to be correct, the pattern of divergence and reduced effective size of Eurasians from Africans is not wholly due to a small group of them leaving the continent at some Middle Pleistocene epoch".

In fact the 'real' OoA goes much further back in time: to Homo erectus. That exit may have involved a 'small group', but even in that case is unlikely to be so. Inbreeding depression would become a huge problem without reinforcement of population by further migrations out of Africa.

"It's time to give up trees and embrace networks!"

I agree! Presumably much the Shenandoah's disgust.

Mark D said...

You make several excellent points, Dienekes, including, "Admixture may not only lead us to overestimate divergence between populations: it might lead us to wrongly estimate the directionality of migration itself."

I have been often troubled by how many have drawn such emphatic conclusions on the source of various groups of peoples in prehistoric times using DNA testing of modern populations. History itself is so full of migrations, back-migrations, invasions, etc. that to discern what happened before then requires much more evidence, genetically, archaeologically, and linguistically than what we have now.

You use North America as problematic for a future geneticist. But consider for example today's Spain. How many invasions and migrations do we know about from historic times? Phoenicians, Greeks, Romans, Suevi, Visigoths, Moors and Jews. We know historically where they came from, but who knows from where came the Celt-Iberians and the Basques. And how much genetic imprint did those historic migrations leave? I have a friend whose paternal line is from Galicia Spain and tested J2b2. Is that a Neolithic tag from a Phoenician or a more recent conversos?

A better example possibly is R1b from Anatolia. Most identify Anatolia as a source or close to source or at least early in the R1b migration. But what mark did the Celtic Galation invasion leave there? There were thousands of migrants who settled there for centuries. If it weren't for historical records on these migrations, would everyone accept that those who test R1b in today's Turkey were original source and not reflective of a Celtic back-migration?

Until we are able to test many more samples of aDNA I would caution those who draw inferences on the direction of prehistoric migrations.

Dr Rob said...

Nice blog

Slumbery said...

Terry

"The 'single origin' of any species has never made any sense to me at all."

Quite the contrary, the splitting of a species to multible new species is virtually impossible if there is significant admixture. In the case of modern and almost modern humans there is no new branch, only and old one that is changing (as all of the existing species do it at different rates). Given enough time you can't call it same species, but still only one branch and unlikely to become two or more with admixture. However we know that new branches always born. Or do you think that life had started with millions of species and their number did not increase with time? There were no common ancestors?



Dienekes

This a very good article. The devil of course will be in the details. I believe that the high variation caused by admixture can be told apart from the high variation of a source population. Eventually, with more data.

Solis said...

Great points, Dienekes.

The Out-of-Africa model is collapsing like a house of cards.

Ponto said...

The problem is everyone thinks in labels for humans. Someone mentioned R1b in Turkey and the Galatians. Surely there is no group of humans who are 100% R1b and never were. Galatians may be more myth than reality, and were probably composed of diverse haplogroups and spoke languages of varying degrees of mutual intelligibility. Pleistocene and early Holocene Europeans were mainly of mitochondrial paragroup U, so the limited ancient dna testing shows, however, it is most likely all West Eurasian and North African humans also belonged to divisions of that mitochondrial paragroup. More testing of ancient remains and better program algorithms will provide more answers provided that with Europeans, that West Eurasians and North Africans are included otherwise the results may be spurious due to limited testing on European ancient remains. That is Europe was never totally separated from its neighbors. By the way, I am still waiting for the answer to the question as to why haplogroup IJ produced hapologroup J in the trans Caucasus region and I in the Balkans.

terryt said...

'Quite the contrary, the splitting of a species to multible new species is virtually impossible if there is significant admixture".

True. But any mutation that leads ultimately to a new species cannot immediately render the individual with it unable to breed with others of its species. Geographic isolation is likely to be the main cause of speciation. However that geographic isolation is very unlikely to involve just a single small subset of any 'original' population.

"In the case of modern and almost modern humans there is no new branch, only and old one that is changing (as all of the existing species do it at different rates)".

If you are prepared to consider the basal human species as Homo erectus than I cannot but agree with you. There are several examples of species that have unusual mt-DNA in that it doesn't fit that expected. For example European bison (or wisent) do not have the same mt-DNA as American bison. It is closer to that of cattle. And American mallard ducks have the same mt-DNA as related species from America rather than Eurasian mallard mt-DNA. In both these cases the new species has obvioulsy not formed from a single isolated group but has involved hybrid formation with other groups. I'm sure many more examples will be found as research on the matter increases.

"Given enough time you can't call it same species, but still only one branch and unlikely to become two or more with admixture".

I think you're regarding the process as being too simple. Even in the chimp/human split we see evience of periods of back-crossing after the 'original' split. I'll find the paper if you're not already aware of it.

"However we know that new branches always born".

Yes, but speciation is no simple matter.

"Or do you think that life had started with millions of species and their number did not increase with time? There were no common ancestors?"

I strongly suspect that even in the remote pre-Cambrian we would not be dealing with just a single species.

terryt said...

"By the way, I am still waiting for the answer to the question as to why haplogroup IJ produced hapologroup J in the trans Caucasus region and I in the Balkans".

Presumably because IJ managed to spread all the way between the Caucasus and the Balkans at some early stage then two subgroups became isolated in each separate region (possibly through ecological change). Then drift took over with IJ drifting to I in the Balkans and J in the Caucasus. That would be my normal interpretation for the spread and diversification of any haplogroup.

Michael Russell said...

'Until recently, tree models dominated models of human demography'.
For mine, one important conclusion is this: The traditional view about Adam and Eve is now utterly dead. (By traditional view, I mean the view that all humans have one man 'Adam' and one woman 'Eve' as common ancestors) Until recently, a traditional view of 'Adam and Eve' was still possible, if unlikely. It was unlikely, since the mtDNA and Y-DNA trees converged at different dates and places.... but with dates and places always within a confidence interval, a common set of ancestors of us all remained perhaps, still viable.
Now, and especially with the Denisovan and Neandertal discoveries - that some humans have 1-3% Neandertal, the traditional Adam and Eve hypothesis is stone dead.
And one way to see that is in the recent move from population models involving trees to admixture studies.
Would you agree?

Dienekes said...

For mine, one important conclusion is this: The traditional view about Adam and Eve is now utterly dead. (By traditional view, I mean the view that all humans have one man 'Adam' and one woman 'Eve' as common ancestors)

Of course all humans have one common patrilineal and one common matrilineal ancestor ("Adam" & "Eve"). There is not way to escape that fact except if one invokes some bizarre theory requiring either polygenesis or special creation.

Michael Russell said...

Yes, of course. I'm still helped by your comment though - sometimes stating the obvious helps.
Maybe I should put it this way: The 1-3% genetic contribution of Neandertals to some modern humans shows that the male MRCA of modern humans lived so far back in time, that he can't possibly be a modern human himself. So 'Adam' as a MRCA isn't in our species.

But this is straying from your post, and heading towards my interests. So thanks for your patience.
PS you wished us happy Easter a while back. Does that mean you believe in God and Jesus?

Dienekes said...

The 1-3% genetic contribution of Neandertals to some modern humans shows that the male MRCA of modern humans lived so far back in time, that he can't possibly be a modern human himself. So 'Adam' as a MRCA isn't in our species.

The Neandertal admixture is irrelevant to the problem of the timing of the Y-chromosome MRCA, since (a) the Y-chromosome MRCA is the common ancestor of modern human Y-chromosomes (and there is not evidence that any modern human Y chromosomes are of Neandertal origin), and (b) we don't have any Neandertal Y chromosomes to work with anyway (the genotyped Neandertal was female).

terryt said...

"Of course all humans have one common patrilineal and one common matrilineal ancestor ('Adam' & 'Eve'). There is not way to escape that fact except if one invokes some bizarre theory requiring either polygenesis or special creation".

I think what Michael is trying to get at is that human ancestry involves more than just the single Y-DNA and mt-DNA ancestors. Other men and women have contributed to the modern genome although their haplogroups have become extinct.

"So 'Adam' as a MRCA isn't in our species".

That is quite possibly so if that 'Adam' lived before 'modern' humans had first appeared. But he is certainly the ancestor of all the surviving human male haplogroups.

"we don't have any Neandertal Y chromosomes to work with anyway (the genotyped Neandertal was female)".

And even if it had been male mt-DNA would have been much more abundant and easier to find that the single Y-chromosome in each cell. I presume it is still very difficult to process ancient Y-chromosomes, although it seems Bronze Age ones are quite possible.