‘Indians have largest variety of Neanderthal, Denisovan genes’

For the first time, scientists from the US, India and Finland have found that Indians derive 1-2 per cent of genes from humans’ archaic relatives, the Neanderthals and the Denisovans. Based on the sequencing of 2,762 genomes from 18 states across the country, the researchers also show that there is a large diversity in archaic ancestry among Indians. These findings, published in a preprint paper on bioRxiv in February 2024, could provide clues to humans’ inherited dispositions, particularly in terms of health, says co-author Priya Moorjani, assistant professor in the Department of Molecular and Cell Biology, University of California, Berkeley, in an interview with Rohini Krishnamurthy. Excerpts:

Rohini Krishnamurthy (RK): What does the study say on the archaic ancestry of Indians?

Priya Moorjani (PM): Our study finds that like most non-Africans, Indians derive 1-2 per cent of their ancestry from gene flow from Neanderthals (who emerged at least 200,000 years ago and inhabited Europe, Africa and Asia) and Denisovans (who emerged about 370,000 years ago in Eurasia). Another surprising finding of our study is that there is a large diversity in archaic ancestry in India. Notably, 90 per cent of Neanderthal sequences found across the world are seen in India. Indians also harbour the largest variation (positioning of genes in the genome) in Denisovan genes among Eurasian populations. This makes Indians quite unique and complex.

From sequencing of Neanderthal and Denisovan genomes, we know that archaic hominins (members of the Hominidae family, of which only one species, Homo sapiens, exists today) interbred with modern humans. And that is the source of Neanderthal and Denisovan ancestries in Indians. Thus, by assembling the bits of Neanderthal or Denisovan ancestry in Indians, we find roughly 1.5 Gb (gigabase, a unit used to measure DNA length), or 50 per cent, of the introgressing Neanderthal genomes (introgressing refers to gradual movement of genes from one species to another) and approximately 0.6 Gb (20 per cent) of the introgressing Denisovan genomes. This is more than any other previous archaic ancestry study.

RK: The study says the proportion of Neanderthal ancestry in Indians (1.48 per cent) is similar to that in Americans (1.4 per cent) and Europeans (1.3 per cent). What explains these comparable results?

PM: We expect that the Neanderthal ancestry proportion would be similar among all non-Africans because the gene flow likely occurred in the common ancestor of all non-Africans. However, it is surprising to see these proportions among modern human groups. What is more puzzling is that the largest variation in Neanderthal ancestry is seen in Indians. The most detailed archaeological work has been done in Europe, and so it is assumed that Neanderthals predominantly lived there, though their range could have extended further south and east. We hope our results lead to a revaluation of the fossil evidence in India and beyond.

RK: Among Indians, do you see differences in the proportion of archaic human genes?

PM: Yes, we do see variation within India. Ancestral South Indian groups have higher amounts of Neanderthal and Denisovan ancestry. However, this is unlikely to be explained by consanguineous marriages (a union between related individuals like second cousins or closer, which is more prevalent in South India). Most Indians have ancestry from ancient groups related to Iranian farmers, Eurasian steppe pastoralists. Indigenous Ancestral South Indian groups are related to Andamanese hunter-gatherers (AHG). We estimate people in India have 20-70 per cent ancestry related to AHG, which is also correlated to the percentage of Neanderthal and Denisovan ancestry.

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Previous studies have shown that Andamanese Islanders have higher Denisovan ancestry, possibly Neanderthal ancestry too, like east Asians. This implies that present-day Indians with higher AHG ancestry also, in turn, have higher Neanderthal and Denisovan ancestry, as we observe in our study.

RK: Can these findings help understand genetic disease susceptibility in India?

PM: In India, we find that Neanderthal ancestry has impacted several immune genes, including a gene cluster on chromosome 3 that impacts response to COVID-19 (A 2020 Nature study finds that people carrying the variant of a gene cluster on chromosome 3, possibly inherited from Neanderthals, have up to three times higher risk of developing severe COVID-19). This region, present in 20-35 per cent of Indians, increases the risk of severe symptoms after COVID-19.

A striking signal of enrichment of Denisovan ancestry in Indians is seen on chromosome 6. This region is part of the human leukocyte antigen or HLA complex and plays a critical role in immune function (HLA complex helps the immune system distinguish proteins made by the body from those by invaders like viruses). At this locus, the frequency of Denisovan ancestry is 9.4 per cent in Indians, which is nearly 100-fold higher than the genome-wide average of roughly 0.1 per cent.

RK: Despite the genetic link of Indians with archaic humans, why have we not found ancient human fossils in India?

PM: As a geneticist, I do not have the expertise to answer this question. But there are challenges to finding ancient fossils such as preservation, urban development and funding. However, if you look at the stone tool culture, there is a large diversity which also reflects the presence of multiple groups. The early Middle Paleolithic (250,000 to 45,000 years ago) stone tool culture in India shows the overlap of distinct cultures—Acheulean hand-axe (produced by the extinct Homo erectus and Homo heidelbergensis) and Levallois technologies (a stone knapping technique associated with at least three hominin populations: late Homo heidelbergensis, Homo neanderthalensis and Homo sapiens)—for over 200,000 years, unlike in other regions of the world.

This was first published in the 16-30 April, 2024 print edition of Down To Earth