Some Indians as genetically diverse as Africans, recent Out of Africa in serious trouble?

Razib alerts me to a very interesting new paper, which discovered that some Indian populations are more diverse than Africans in a sequenced 100kb region. I will have much more to say about this once I digest it fully, but as I said in my recent review of the Oceania paper, I don't believe in long "interludes" of humans living Africa and then spending tens of thousands of years camping in one place before starting to expand again. I don't believe that there is evidence for Neandertal admixture in Eurasians either; the title of my post hints at what I believe. Update to follow.

Thanks to the Jorde Lab for putting up their genotype data easily accessible online! They're an example for others to follow.

UPDATE:

Here is the crux of the paper:

As previously observed, heterozygosity (a measure of genetic diversity) decreases with distance from East Africa (represented here by the Luhya LWK HapMap poopulation). The only trouble is, that this pattern disappears once the Indian populations are included in the analysis.

Things are even worse though: the Luhya are an admixed population. Thus, their level of heterozygosity is inflated because of their relatively recent admixture associated with the spread of Bantu languages. Remove them, and it's clear the pattern of diminution of genetic diversity from East Africa completely disappears. Indeed, I am convinced that this pattern may be completely due to the admixed status of East Africans; the Maasai are another HapMap population from East Africa that seems to be missing from this analysis, and it is less heterozygous than the Luhya.

Even though the pattern of diminution of genetic diversity from East Africa (in autosomal genes, at least) may be largely due to the admixed status of East Africans, the same could be true for the Indian groups, who are largely composed of an indigenous "Ancestral South Indian", and an invasive "Ancestral North Indian" component. But, the point is that these two groups must have been substantially differentiated to produce a larger level of heterozygosity than in the Africans.

A caveat should be registered: genetic diversity in African hunter-gatherers (Bushmen and Pygmies) may be even higher than in the Yoruba and Luhya. Also, the mtDNA phylogeny is pretty unambiguous about the matrilineal origin of humanity being in Africa. And, the earliest known fossils of anatomically modern humans are in Africa. Thus, some kind of Out-of-Africa scenario still finds support in the data.

What does no longer find support in the data is the idea of a recent Out-of-Africa exodus 40-60 thousand years ago. The authors of the current paper:

the divergence time between African and the ancestral Eurasian population (88-112 kya, CIs: 63-150 kya) is much older than the divergence time among the Eurasian groups (27-39 kya, CI: 20-59 kya).

A divergence between Africans and Eurasians 100ky is consistent with the paleoanthropological finds from the Levant and China, showing the presence of anatomically modern humans thousands of kilometers apart at that time outside Africa. If there was an Out of Africa, it happened 100 thousand years ago.

The second important point is that the supposed maintainance of a Eurasian population outside Africa in the Levant for tens of thousands of years before the breakup of the Eurasians:

There are serious reasons to doubt this hiatus:

First, the presence of AMH in China in the Levant and China 100,000 years ago is hardly consistent with the maintainance of a geographically circumscribed population of Eurasians in the Levant until 40,000 years ago.

Second, it is hardly parsimonious that such a population would maintain itself in a geographically circumscribed area for so long. If they moved from East Africa to the Near East, why on earth would they stop there?

In my opinion two underappreciated factors should be considered:

• Gene flow within Eurasia reduces divergence times between Eurasians; West, South, and East Eurasians did not branch out from a common ancestor; there were episodes of gene flow between them, some of them very recent, some of them beyond any record. Such lateral gene flow did not abolish differences between them, but it would have reduced the inferred divergence time.
• Gene flow between Afrasians (i.e., Eurasians' unadmixed ancestors in East Africa) and other Palaeoafricans inhabiting other parts of the continent would have increased the inferred divergence time between Africans and Eurasians.

These two factors might suffice to explain the observed pattern, without invoking a long hiatus.

Genome Biology 2010, 11:R113 doi:10.1186/gb-2010-11-11-r113

Genetic diversity in India and the inference of Eurasian population expansion

Jinchuan Xin et al.

Abstract (provisional)
Background
Genetic studies of populations from the Indian subcontinent are of great interest because of India's large population size, complex demographic history, and unique social structure. Despite recent large-scale efforts in discovering human genetic variation, India's vast reservoir of genetic diversity remains largely unexplored.

Results
To analyze an unbiased sample of genetic diversity in India and to investigate human migration history in Eurasia, we resequenced one 100 kb ENCODE region in 92 samples collected from three castes and one tribal group from the state of Andhra Pradesh in south India. Analyses of the four Indian populations, along with eight HapMap populations (692 samples), showed that 30% of all SNPs in the south Indian populations are not seen in HapMap populations. Several Indian populations, such as the Yadava, Mala/Madiga, and Irula, have nucleotide diversity levels as high as those of HapMap African populations. Using unbiased allele-frequency spectra, we investigated the expansion of human populations into Eurasia. The divergence time estimates among the major population groups suggest that Eurasian populations in this study diverged from Africans during the same time frame (approximately 90-110 thousand years ago). The divergence among different Eurasian populations occurred more than 40,000 years after their divergence with Africans.

Conclusions
Our results show that Indian populations harbor large amounts of genetic variation that have not been surveyed adequately by public SNP discovery efforts. Our data also support a delayed expansion hypothesis in which an ancestral Eurasian founding population remained isolated long after the out-of-Africa diaspora, before expanding throughout Eurasia.

Link

ADMIXTURE on African HapMap populations

Here is the result of running ADMIXTURE on the three African HapMap-3 populations, using about 440K SNPs, including Tuscans as a non-African group.

The Tuscans are in purple and show no trace of African admixture. All the other populations are separated: red: Luhya (Bantu); green: Maasai (Nilotes); Yoruba (Niger-Congo).

The two east African groups show asymmetrical affinities: the Maasai have some Luhya red, while the Luhya have little Maasai green, while they have substantial West African turqoise, consistent with the origin of their Bantu language.

Related: ADMIXTURE on HapMap-3 populations

ADMIXTURE on HapMap 3 populations

Here is the result of running ADMIXTURE on about ~50K markers from the HapMap 3 populations. I'll annotate the final K=9 run; the rest are given at the end:

I list the distinctive colors for the populations, Left-to-Right. The minor components are easy enough to pick up and as expected:

ASW (A): African ancestry in Southwest USA [Sub-Saharan blue]

CEU (C): Utah residents with Northern and Western European ancestry from the CEPH collection [European yellow]

CHB (H): Han Chinese in Beijing, China [East Asian orange]
CHD (D): Chinese in Metropolitan Denver, Colorado [East Asian orange]

GIH (G): Gujarati Indians in Houston, Texas [South Asian purple]

JPT (J): Japanese in Tokyo, Japan [East Asian light green]

LWK (L): Luhya in Webuye, Kenya [East African bright green]

MEX (M): Mexican ancestry in Los Angeles, California [Amerindian pink]

MKK (K): Maasai in Kinyawa, Kenya [East African light blue]

TSI (T): Tuscan in Italy [European yellow]

YRI (Y): Yoruban in Ibadan, Nigeria (West Africa) [Sub-Saharan blue]

The rest of the runs for K=3 to K=8 are below:

K=3: Notice: Asian red+Caucasoid blue on Gujarati Indians and Mexicans. At this level of resolution, these two populations look similar. Notice presence of blue in East Africans but not Yorubans (green at the end).

K=4: East Africans get their own (yellow) cluster. Notice the diminution of the Sub-Saharan (purple) element, relative to the previous figure. This is due to the fact that the East African element is intermediate between Caucasoids and Sub-Saharans and "eats up" the other two elements, although residual Caucasoid red and Sub-Saharan purple remains. The tripartite origin of Mexicans is especially visible in this plot, with components being in order of European, East Eurasian, Sub-Saharan.
K=5: Gujarati Indians now get their own (purple) cluster. Here the difference between Luhya (mostly Sub-Saharan blue + East African yellow) and Maasai (the reverse) is quite striking. The former are Bantu speakers and thus not indigenous to east Africa.
K=6: Mexicans get their own cluster (blue) reflecting their Amerindian, rather than East Asian ancestry which could not be resolved in the previous figures.
K=7: the Luhya get their own cluster, splitting off from the Maasai. There are now 3 components in Africa centered on Yorubans (light blue), Luhya (very light green) and Maasai (red).
K=8: A low-frequency element appears in Maasai that is hard to interpret; it is preserved in the next and final K=9 run (shown at the beginning of the post), in which the Japanese and Chinese are split off.

More Uniform Sampling of Human Genetic Diversity (Xing et al. 2010)

Some observations on the paper:

New World populations (Totonac and Bolivian) are placed between Nepalese and Kyrgyzstanis, indicating higher affinity of these American samples to central Asians than to eastern Asians.

This is more likely an artifact of the mixed (Caucasoid-Amerindian) ancestry of these American samples, rather than an indication of their Central Asian origin, as the authors seem to believe. This is an important caveat, as American Indians and Central Asians are "pulled together" by their shared West Eurasian ancestry of post-Columbus and Neolithic/Chalcolithic Age origin respectively, and correspondingly "pulled away" by Mongoloids proper from East Asia who lack that admixture.

Polynesians also deviate from East Asians towards Europeans, less strongly than Central Asians, and this reflects low-level admixture between ancestral Polynesians and colonial-era Europeans.

The Eurasian PCA is interesting:

At the sub-continental level, we focus first on Eurasia, where most of our samples have been selected (Figure 4A). Overall, PC1 and PC2 mainly reflect the geographic distribution of the populations, with the majority of genetic variation accounted for by their locations. PC1 (accounting for 62.7% of the variance) reflects an east-west gradient, while PC2 (3.3% of the variance) reflects a north-south gradient.

There is absolutely no reason (based on geographical distance) for PC1 to account for twenty times more variance than PC2. PC1 reflects the racial contrast between Caucasoids and Mongoloids, while PC2 reflects the much weaker latitudinal adaptation and south-to-north spread of humans into the higher latitudes.

Another thing to notice is how tightly clustered Caucasoids are, from the Atlantic to Iraq (a distance of about 4,000km), which is -conservatively- about half the distance between Pakistan and South India. This is due to the fact that South Asians were formed by admixture of two elements: an extraneous Caucasoid one and an indigenous Paleo-Indian one. Notice also that this variable admixture (highest Caucasoid component in Brahmins) is not really compatible with an indigenous origin of the caste system, as has been proposed on non-scientific grounds.

More spread (given geographical distance) is also observed in Central Asia and Southeast Asia, and this is explained by relatively recent admixture between Caucasoids and Mongoloids (in the former) and Paleo-Indian-like morphological "Australoids" and Mongoloids (in the latter).

The results of ADMIXTURE analysis (for Eurasian individuals) are presented in graphical format in the paper itself, for (K=7).

Not much to comment on this that hasn't been seen before:

One observation is the existence of some "red" West Asian component in the N. European sample, which is not found in Slovenians. This may parallel the peculiarity of the Caucasoid components observed for Russians and Lithuanians recently, although the several Caucasoid components detected in that study are folded into 2 in the current one.

Notice also, how "red" is the main extraneous component in Indian Brahmins. As expected, even Brahmins are predominantly of "indigenous" origin, as these Brahmins are from Tamil Nadu and Andhya Pradesh, and not from North India. The West Asian affiliations of the main Caucasoid component are evident, and agree with Behar et al. (2010) where South Asians had a major overlap with West Asians (light green) and a minor one with Europeans (dark blue). In this paper, with a lower K the different European and West Asian subclusters are not visible.

The most interesting part of the study -for me- was the inclusion of three novel African samples, the Luhya, Alur, and Hema. Notice the blue component in these people, which resolves partially to orange at K=12. This is an indication of Eurasian affinities that are mostly lacking in other black Africans.

The Luhya are Bantu speakers from Kenya, so they are not indigenous to East Africa, but have probably picked up some native East African ancestry from their non-Bantu neighbors.

The Hema are from the Democratic Republic of Congo, but they are Nilo-Saharan pastoralists. Their fairly noticeable West Eurasian component may reflect origins outside the Congo. Are these another member of the non-Bantu pastoralists expanding from East Africa to the south? It would be interesting to take a look at these people's Y chromosomes.

All in all, a very interesting paper which adds important new populations to the discussion of human origins. Also of note, the free availability of the paper's genotype data and supplementary material at the Jorde Lab.

Genomics doi:10.1016/j.ygeno.2010.07.004

Toward a more uniform sampling of human genetic diversity: A survey of worldwide populations by high-density genotyping

Jinchuan Xing et al.

High-throughput genotyping data are useful for making inferences about human evolutionary history. However, the populations sampled to date are unevenly distributed, and some areas (e.g., South and Central Asia) have rarely been sampled in large-scale studies. To assess human genetic variation more evenly, we sampled 296 individuals from 13 worldwide populations that are not covered by previous studies. By combining these samples with a data set from our laboratory and the HapMap II samples, we assembled a final dataset of ~ 250,000 SNPs in 850 individuals from 40 populations. With more uniform sampling, the estimate of global genetic differentiation (FST) substantially decreases from ~ 16% with the HapMap II samples to ~ 11%. A panel of copy number variations typed in the same populations shows patterns of diversity similar to the SNP data, with highest diversity in African populations. This unique sample collection also permits new inferences about human evolutionary history. The comparison of haplotype variation among populations supports a single out-of-Africa migration event and suggests that the founding population of Eurasia may have been relatively large but isolated from Africans for a period of time. We also found a substantial affinity between populations from central Asia (Kyrgyzstani and Mongolian Buryat) and America, suggesting a central Asian contribution to New World founder populations.

Link