Genetic History of India

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Genetic History of India Dec 29, 2021 2:31:30 GMT

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Post by Admin on Dec 29, 2021 2:31:30 GMT

Functional Impact
A small proportion of SNVs have a predicted functional impact (Supplementary Figs. 20–23, Supplementary Tables 11–14, Supplementary Note, and Supplementary Data File). Among 60,555 SNVs, we observed two singleton premature stop-codons, one each in AMELY and USP9Y, and one splice-site SNV that affects all known transcripts of TBL1Y. Among 94 missense SNVs with SIFT19 scores, all 30 deleterious variants are singletons or doubletons, while 17/64 tolerated variants are present at higher frequency (p = 0.001), underscoring the impact of purifying selection on variation at protein-coding genes. No STRs overlapped protein-coding regions, but, in contrast to the SNVs, a high proportion of CNVs have a predicted functional impact.

Twenty of 100 CNVs in our final callset overlap with 27 protein-coding genes from 17 of the 33 Y-chromosome gene families. In our analysis of 1000 Genomes Project autosomal data, we observed that the ratio of the proportion of deletions overlapping protein-coding genes to the proportion of duplications overlapping protein-coding genes is 0.84. Whereas on the autosomes deletions are less likely to overlap protein-coding genes than duplications are, as others have also reported20, we found the reverse to be true for the Y chromosome. Despite its haploidy, we calculated its ratio of proportions to be 1.5, indicating a surprising increased tolerance of gene loss, as compared with the diploid genes on autosomes.

Diversity
Given observed diversity levels of the autosomes, the X chromosome, and the mitochondrial genome (mtDNA) (Supplementary Table 15, Supplementary Note, and Supplementary Data File), Y-chromosome diversity was reported to be lower than expected from simple population-genetic models that assume a Poisson-distributed number of offspring4, and the role of selection in this disparity is debated. We confirmed that Y-chromosome diversity in our sample is low (Supplementary Fig. 24) and found that positing extreme male-specific bottlenecks in the last few millennia can lead to a good fit between modeled and observed relative diversity levels of the autosomes, the X chromosome, the Y chromosome, and the mtDNA (Supplementary Figs. 25–28, Supplementary Table 16, and Supplementary Note). Therefore, we conclude that Y diversity may be shaped primarily by neutral demographic processes.

Haplogroup Expansions
To investigate punctuated bursts within the phylogeny and estimate growth rates, we modeled haplogroup growth as a rapid phase followed by a moderate phase and applied this model to lineages showing rapid expansions (Supplementary Figs. 29–31, Supplementary Tables 17–19, Supplementary Note, and Supplementary Data File), noting that such extreme expansions are seldom seen in the mtDNA phylogeny here or in other studies5. We examined 20 nodes of the tree whose branching patterns were well-fit by this model. These nodes were drawn from eight haplogroups and included at least one lineage from each of the five continental regions surveyed (Fig. 4). As the haplogroup expansions we report are among the most extreme yet observed in humans, we think it more likely than not that such events correspond to historical processes that have also left archaeological footprints. Therefore, in what follows, we propose links between genetic and historical or archaeological data. We caution that, especially in light of as yet imperfect calibration, these connections remain unproven. But they are testable, for example using aDNA.

Figure 4
Explosive male-lineage expansions of the last 15 thousand years. Each circle represents a phylogenetic node whose branching pattern suggests rapid expansion. The x-axis indicates the timings of the expansions, and circle radii reflect growth rates—the minimum number of sons per generation, as estimated by our two-phase growth model. Nodes are grouped by continental superpopulation (AFR, African; AMR, Admixed American; EAS, East Asian; EUR, European; SAS, South Asian) and colored by haplogroup. Line segments connect phylogenetically nested lineages.

First, in the Americas, we observed expansion of Q1a-M3 (Supplementary Figs. 14e and 17) at ~15 kya, the time of the initial colonization of the hemisphere21. This correspondence, based on one of the most thoroughly examined dates in human prehistory, attests to the suitability of the calibration we have chosen. Second, in sub-Saharan Africa, two independent E1b-M180 lineages expanded ~5 kya (Supplementary Figs. 14a), a period before the numerical and geographical expansions of Bantu speakers in whom E1b-M180 now predominates22. The presence of these lineages in non-Bantu speakers (e.g., Yoruba, Esan) indicates an expansion pre-dating the Bantu migrations, perhaps triggered by the development of ironworking23. Third, in Western Europe, related lineages within R1b-L11 expanded ~4.8–5.9 kya (Supplementary Figs. 14e), most markedly around 4.8 and 5.5 kya. The earlier of these times, 5.5 kya, is associated with the origin of the Bronze Age Yamnaya culture. The Yamnaya have been linked by aDNA evidence to a massive migration from the Steppe, which may have replaced much of the previous European population24,25, but the six Yamnaya with informative genotypes did not bear lineages descending from or ancestral to R1b-L11, so a Y-chromosome connection has not been established. The later time, 4.8 kya, coincides with the origins of the Corded Ware (Battle Axe) culture in Eastern Europe and the Bell-Beaker culture in Western Europe26.

Potential correspondences between genetics and archaeology in South and East Asia have received less investigation. In South Asia, we detect eight lineage expansions dating to ~4.0–7.3 kya and involving haplogroups H1-M52, L-M11, and R1a-Z93 (Supplementary Figs. 14b, 14d, and 14e). The most striking are expansions within R1a-Z93, ~4.0–4.5 kya. This time predates by a few centuries the collapse of the Indus Valley Civilization, associated by some with the historical migration of Indo-European speakers from the western steppes into the Indian sub-continent27. There is a notable parallel with events in Europe, and future aDNA evidence may prove to be as informative as it has been in Europe. Finally, East Asia stands out from the rest of the Old World for its paucity of sudden expansions, perhaps reflecting a larger starting population or the coexistence of multiple prehistoric cultures wherein one lineage could rarely dominate. We observed just one notable expansion within each of the O2b-M176 and O3-M122 clades (Supplementary Figs. 14d).

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Genetic History of India Dec 29, 2021 3:45:27 GMT

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Post by Admin on Dec 29, 2021 3:45:27 GMT

Discussion
The 1000 Genomes Project dataset provides a rich and unparalleled resource of Y-chromosome variation coupled with open access to DNA and cell lines that will facilitate diverse further investigations. By cataloging the phylogenetic position of ~60,000 SNVs, we have constructed a database of diagnostic variants with which one can assign Y-chromosome haplogroups to DNA samples (Supplementary Data File). This resource is particularly valuable for SNP-chip design and for aDNA studies, in which sequencing coverage is often quite low, as exemplified by our reanalysis of the Ust’-Ishim and Oase1 Y chromosomes.

The variants we report have well-calibrated FDRs. Nevertheless, due to the modest sequencing coverage, data missingness was a principal concern. Small CNVs and long STRs are largely undetected, and low frequency variants in general, including SNVs, are under-represented. We therefore took great care to minimize the impact of missing variants. In particular, we designed the relevant downstream analyses to only use information from higher frequency, shared, variation, corresponding to mutations on internal branches of the tree.

Since many DNA samples were extracted from lymphoblastoid cells, another potential concern was variation that has arisen during cell culture28. However, these false discoveries are inherently not shared. Therefore, the precautions we took to minimize the impact of missingness also precluded in vitro mutations from influencing our findings. We discuss additional caveats on the mapping of SNVs to branches in the Supplementary Note.

Our findings illustrate unique properties of the Y chromosome. Foremost, the abundance of extreme male-lineage expansions underscores differences between male and female demographic histories. A caveat to our expansion analysis is that our inference method assumes that population structure did not affect the branching patterns immediately downstream of the particular phylogenetic node under investigation. This is reasonable, because population structure is unlikely when a very rapid expansion is in progress, but to accommodate this strong assumption, we limited all analyses to pruned internal subtrees short enough for it to hold. A second caveat regards the choice of calibration metric, which is relevant to the links we have suggested between expansions and historical or archaeological events. Present-day geographical distributions provide strong support for the correspondences we proposed for the initial peopling of most of Eurasia by fully modern humans ~50–55 kya and for the first colonization of the Americas ~15 kya. For later male-specific expansions, we should consider the consequences of alternative mutation rate estimates, as pedigree-based methods relying on variation from the most recent several centuries8,10,28 may be more relevant. The pedigree-based estimate from the largest set of mutations8 would lead to a decrease in expansion times by ~15%, increasing the precision of the correspondences proposed for E1b and R1a. For R1b, a 15% decrease would suggest an expansion postdating the Yamnaya migration, perhaps better explaining the distinction between the Yamnaya R1b chromosomes and the expanding R1b-L11 lineage. Either way, the lineage expansions seem to have followed innovations that may have elicited increased variance in male reproductive success29, innovations such as metallurgy, wheeled transport, or social stratification and organized warfare. In each case, privileged male lineages could undergo preferential amplification for generations. We find that rapid expansions are not confined to unusual circumstances30,31. Rather, they can dominate on a continental scale and do so in some of the populations most studied by medical geneticists. Inferences incorporating demography may benefit from taking these male-female differences into account.

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Genetic History of India Jan 5, 2022 18:44:42 GMT

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Post by Admin on Jan 5, 2022 18:44:42 GMT

Two recent papers- The Formation of Human Populations in South and Central Asia (Vageesh Narasimhan et al) and An Ancient Harappan Genome lacks Ancestry from Steppe Pastoralists or Iranian Farmers (Vasant Shinde et al) - have sparked different interpretations on what they reveal about the genetics of ancient Indians. The papers were authored by a team of geneticists from Harvard Medical School working with Indian scientists. They studied ancient DNA from sites in Europe, Central Asia and South Asia, including a sample from the Indus Valley Civilisation site of Rakhigarhi, before drawing their conclusions. One of which was the contested claim that descendants of pastoralists from Eurasian steppes migrated to the Indian subcontinent in the first half of the second millenium BCE, "almost certainly" bringing Indo-European languages. Their studies also claim the Steppe migrants eventually contributed 0-30% of the genes of groups living in India today. In an email interview, Harvard geneticist Prof David Reich breaks down the findings. Excerpts.

1) What are the big takeaways from the 2 recent studies you co-authored - Vasant Shinde et al 2019, and Narasimhan et al 2019?

1. At least some of the people of the ancient people of the Indus Valley Civilization were a mixture of south/southeast Asian-related hunter gatherers and Iranian-related hunter-gatherers. I say Iranian-related because their ancestors may actually have lived in South Asia rather than the Iranian plateau for many thousands of years before the time of the IVC. We just don’t know yet where they lived because of lack of ancient DNA from the relevant times and places.

2. A population like the people we call the “Indus Valley Cline” - consisting of a Harappan individual from the site of Rakhigarhi, plus 11 individuals who were buried at the sites of Gonur in Turkmenistan and Shahr-i-Sokhta in Iran and as likely migrants from the Indus Valley Civilization — is the primary source population of both North and South India.

3. Some time in the first half of the second millennium BCE, descendants of Steppe pastoralists entered South Asia from the north, eventually contributing 0-30% of the genes of groups living today (varying depending on the present-day group), and also almost certainly bringing Indo-European languages. There is no evidence that the actual people who brought these genes to South Asia were pastoralists by occupation - their ancestors were pastoralists.

2) What more can you tell us from your studies about this Steppe migration? Mostly male? Was it a significant number - so as to make such drastic changes in the gene pool of such a large area?

It is entirely plausible, and in my opinion even likely, that the movement of people bringing this ancestry to the Indian subcontinent was not sex-biased, and involved both males and females. However, the process by which people carrying this ancestry mixed with people with ancestry like the individual from Rakhigarhi, was a sex-biased one, whereby most of the Steppe ancestry to mixed population was contributed by males. Note that according to our paper, in the Swat Valley, Steppe ancestry mixes into South Asia in a sex-biased way but in the REVERSE pattern, that is, most of the Steppe ancestry is coming from females.

"In the Late Bronze Age and Iron Age individuals of the Swat Valley, we detect a significantly lower proportion of Steppe admixture on the Y chromosome (only 5% of the 44 Y chromosomes of the R1a-Z93 subtype that occurs at 100% frequency in the Central_Steppe_MLBA males) compared with ~20% on the autosomes (Z = −3.9 for a deficiency from males under the simplifying assumption that all the Y chromosomes are unrelated to each other since admixture and thus are statistically independent), documenting how Steppe ancestry was incorporated into these groups largely through females (Fig. 4). However, sex bias varied in different parts of South Asia, as in present-day South Asians we observe a reverse pattern of excess Central_Steppe_MLBA–related ancestry on the Y chromosome compared with the autosomes (Z = 2.7 for an excess from males).”

These differences could be explained by a non-sex-biased migration from Central Asia into South Asia of people carrying Steppe ancestry, followed (at some point later) by preferential incorporation of females from this population into the Swat Valley peoples, and preferential incorporation of males from this population into the ancestors of most present-day South Asians.

3) When did they reach the Indian subcontinent?

We know this rather precisely from our analysis: the first half of the second millennium BCE.

4) Was this the 'collision' that formed present day Indian populations?

This is one of at least four major collisions we now know about:

a. The mixture of Iranian-related ancestry and South/Southeast Asian hunter-gatherer-related ancestry that formed the Indus Valley Cline on average 7400-5700 years ago.

b. The mixture of people on the Indus Valley Cline with people from the southeast carrying relatively more South/Southeast Asian hunter-gatherer-related ancestry after the decline of the mature Indus Valley Civilization around 4000-3000 years ago

c. The mixture of people on the Indus Valley Cline with people from the north carrying Steppe ancestry after the decline of the mature Indus Valley Civilization around 4000-2000 years ago

d. The mixture of these two mixed populations (b and c)

There are surely more collisions yet to be discovered!

5) And what was the route to the Indian subcontinent? From the Yamnaya culture in Eastern Europe to the Central steppes (BMAC) and then to South Asia?

The exact routes are currently unknown. Almost certainly it started in far eastern Europe more than 5000 years ago (with the Yamnaya or their close relatives), then 4500-4000 years ago moved possibly west to east-central Europe (but this westward-before-eastward deviation is not certain), and then moved far to the east across the Urals to the central Steppe (Kazakhstan) and Central Asia (places like Turkmenistan) before moving into South Asia 4000-3500 years ago.

It is likely, based on our analysis, that the population that contributed genetic material to South Asia was (roughly) ~60% Yamnaya, ~30% European farmer-like ancestry, and ~10% Central Steppe hunter-gatherer ancestry.

6) What difference, according to your study, did it make to the Indus Valley Civilisation gene pool ?

This ancestry admixed with people like those we sequenced from the Indus Valley Civilization, eventually contributing 0-30% Steppe-derived ancestry to present-day populations.

7) Was it the contrast in the genetic profiles of later Indian (South Asian) people and that of the 2600 BC Rakhigarhi woman and the 11 other Indus Valley people (discovered at sites related to IVC) that helped you get this picture?

Yes. With these individuals, we for the first time found ancient people who could serve as a statistically fitting genetic source for the largest component of ancestry in South Asian (the Iranian-related ancestry)

8) Does your Rakhigarhi study 'An Ancient Harappan Genome lacks Ancestry from Steppe Pastoralists or Iranian Farmers' in any way contrast the findings of your other ( Narasimhan et al) study 'The Formation of Human Populations in South and Central Asia'.

The two studies are fully consistent. I am confident that there are no contradictions.

9) Digs at the Indus Valley site Rakhigarhi, from where the woman's skeletal remains were discovered show an archaeological continuity. No signs of destruction. Is it possible to have a shift in a population and even possibly a change in civilisation without a disruption in material culture? Have you see that happen elsewhere?

This is entirely possible. We discuss this explicitly in our paper by making an analogy to a major and slightly earlier cultural and genetic transformation in western Europe, where we know more accurately what happened because of a richer ancient DNA record

“If the spread of people from the Steppe in this period was a conduit for the spread of South Asian Indo-European languages, then it is striking that there are so few material culture similarities between the Central Steppe and South Asia in the Middle to Late Bronze Age (i.e., after the middle of the second millennium BCE). Indeed, the material culture differences are so substantial that some archaeologists report no evidence of a connection. However, lack of material culture connections does not provide evidence against spread of genes, as has been demonstrated in the case of the Beaker Complex, which originated largely in western Europe but in Central Europe was associated with skeletons that harbored ~50% ancestry related to Yamnaya Steppe pastoralists (18). Thus, in Europe we have an unambiguous example of people with ancestry from the Steppe making profound demographic impacts on the regions into which they spread while adopting important aspects of local material culture. Our findings document a similar phenomenon in South Asia, with the locally acculturated population harboring up to ~20% Western_Steppe_EMBA–derived ancestry according to our modeling (via the up to ~30% ancestry contributed by Central_Steppe_MLBA groups)”

10) You've said that people who formed the population of the IVC is the single largest genetic contributor to people living in South Asia today? Can you elaborate?

The great majority of present-day South Asians are a mixture of two source populations that formed after the decline of the Indus Valley Civilization: the Ancestral South Indians (ASI) and the Ancestral North Indians (ANI). In our paper (Figure 4D), we show that the ASI and ANI both have high proportions of Indus Valley Cline ancestry (similar to that of the Rakhigarhi individual). Depending on the particular model used, this number could range from 30-60% for the ASI, and very roughly around 70% for the ANI. Since present-day South Asians are largely a mixture of ANI and ASI who in turn both have major proportions of Indus Valley Cline-type ancestry, this is the largest source of ancestry in present-day South Asians.

Last Edit: Jan 5, 2022 18:45:25 GMT by Admin

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Genetic History of India Jan 5, 2022 21:24:47 GMT

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Post by Admin on Jan 5, 2022 21:24:47 GMT

The Formation of Human Populations in South and Central Asia

Abstract
By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and southeast Asia. Following the Indus Valley Civilization’s decline, they mixed with people in the southeast to form one of the two main ancestral populations of South Asia whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who spread via Central Asia after 4000 years ago to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the unique shared features shared between Indo-Iranian and Balto-Slavic languages.

Graphical Abstract

The Bronze Age spread of Yamnaya steppe pastoralist ancestry into two subcontinents, Europe and South Asia. Pie charts reflect the proportion of Yamnaya ancestry, and dates reflect the earliest available ancient DNA with Yamnaya ancestry in each region. There is no ancient DNA yet for the ANI and ASI, so for these the range is inferred statistically.

One Sentence Summary:
Genome wide ancient DNA from 523 ancient individuals sheds light on genetic exchanges between the Steppe, Iran and South Asia, and highlights the parallel demographic histories of two subcontinents: Europe and South Asia.

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Genetic History of India Jan 5, 2022 22:29:32 GMT

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Post by Admin on Jan 5, 2022 22:29:32 GMT

One Page Summary
Introduction and Rationale:
To elucidate the extent to which the major cultural transformations of farming, pastoralism and shifts in the distribution of languages in Eurasia were accompanied by movement of people, we report genome-wide ancient DNA data from 523 individuals spanning the last 8000 years mostly from Central Asia and northernmost South Asia.

Results:
Movements of people following the advent of farming resulted in genetic gradients across Eurasia that can be modeled as mixtures of seven deeply divergent populations. A key gradient formed in southwestern Asia beginning in the Neolithic and continuing into the Bronze Age, with more Anatolian farmer-related ancestry in the west and more Iranian farmer-related ancestry in the east. This cline extended to the desert oases of Central Asia and was the primary source of ancestry in peoples of the Bronze Age Bactria Margiana Archaeological Complex (BMAC). This supports the idea that the archaeologically documented dispersal of domesticates was accompanied by the spread of people from multiple centers of domestication.

The main population of the BMAC carried no ancestry from Steppe pastoralists and did not contribute substantially to later South Asians. However, Steppe pastoralist ancestry appeared in outlier individuals at BMAC sites by the turn of the second millennium BCE around the same time as it appeared on the southern Steppe. Using data from ancient individuals from the Swat Valley of northernmost South Asia, we show that Steppe ancestry then integrated further south in the first half of the second millennium BCE, contributing up to 30% of the ancestry of modern groups in South Asia. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the unique shared features shared between Indo-Iranian and Balto-Slavic languages.

The primary ancestral population of modern South Asians is a mixture of people related to early Holocene populations of Iran and South Asia that we detect in outlier individuals from two sites in cultural contact with the Indus Valley Civilization (IVC), making it plausible that it was characteristic of the IVC. After the IVC’s decline, this population mixed with northwestern groups with Steppe ancestry to form the “Ancestral North Indians” (ANI) and with southeastern groups to form the “Ancestral South Indians” (ASI) whose direct descendants live today in tribal groups in southern India. Mixtures of these two post-IVC groups--the ANI and ASI--drive the main gradient of genetic variation in South Asia today.

Conclusion:
Earlier work recorded massive population movement from the Steppe into Europe early in the 3rd millennium BCE, likely spreading Indo-European languages. We reveal a parallel series of events leading to the spread of Steppe ancestry to South Asia, thereby documenting movements of people that were likely conduits for the spread of Indo-European languages.