UChicago geneticist uses more than just DNA to explore ancient human history

You’ve probably never met ancestors older than your grandparents or great grandparents, but you may know something about them. Maybe your grandmother once told you that her ancestors came from a different home country than you do. She uses this to explain your family’s unique customs: the food you cook, the language you speak, the clothes you wear. This is a form of oral history.

Later, you send a saliva sample to a genetic ancestry company, but when you get your results, you see no evidence of that migration. Now, you’re confused about your heritage. Are your family’s oral histories and customs wrong? And just how much can you trust these genetic sequencing companies anyway?

Maanasa Raghavan, PhD, Neubauer Family Assistant Professor of Human Genetics at the University of Chicago, works at the crossroads of these different sources of history. Using population genetics methods on both modern populations and ancient DNA samples, her lab investigates how a population’s demographic, cultural, and environmental history is reflected in its genetic profiles.

In a new study published in Human Genetics and Genomics Advances, Raghavan and her team discuss how population identities can be learned from various sources, and how human geneticists can responsibly interpret and report genetic evidence that is at odds with a population’s self-identity.

“When you’re doing genetic analyses in the context of population origins, it’s very hard to escape the socio-cultural angle of self-identity, because often how we consider these communities and decide our sampling in anthropological genetics comes from those designations,” Raghavan said. “And it's very rare to these different lines of knowledge being integrated in a way where they don’t all agree with each other.”

The team surveyed the genetics of different communities along the southwestern coast of India, namely the Kodava, Bunt, and Nair people. These communities constitute an under-studied and under-sampled contingent of the already sparsely sampled region of South Asia.

Part of what makes these communities interesting, however, is that they are all thought to have a distinct genetic origin compared to other South Asian peoples. Over thousands of years, migrations of different ancient communities to the subcontinent resulted in multiple instances when migrant and local populations genetically mixed. Therefore, modern South Asian populations are all thought to carry different proportions of ancient Eastern and Western Eurasian ancestry from migrations that occurred thousands of years ago to more recent times. The Kodava, Bunt, and Nair people, per their oral histories, all claim more recent ancestry from Western Eurasians, however, some citing the nomadic Scythians from the Iron Age, and some citing members of Alexander the Great’s army.

While this aspect of their oral histories is yet to be thoroughly investigated by anthropologists, these three communities also stand out for their cultural practices. While current members of the communities have adopted more mainstream Hindu customs, ancestor worship remains a strong component of their religion. Additionally, the Bunt and Nair communities are among the very few matrilocal communities in the world, in which inheritance passes through the maternal, rather than paternal, line. The Kodava people are also known to have unique wedding and naming customs.

The Raghavan lab performed genome-wide sequencing of saliva samples from members of each community and determined their genetic relationships to other modern Indian populations, as well as ancient Indian and Eurasian ones. Interestingly, they found that Kodava, Bunt, and Nair people were genetically most similar to each another, and to many other Indian populations. Yet, their genetic profiles did not show any strong relationship to Western Eurasian populations as recent as Alexander’s time, i.e., 400 BCE.

So how do the researchers interpret these results?

“One way was to just say, ‘The oral histories do not match with genetic histories,’ and leave it at that, potentially subjecting these communities to people questioning their self-identities, and exposing them to further marginalization,” Raghavan said. “But we wanted to suggest an alternative to the assumption that genetics methods and their findings trump all other forms of knowledge. Rather, we should understand that genetics reflects biological evolutionary processes and that other forms of knowledge reflect other processes.”

The “other processes” here refer to contact between communities that is not genetic, such as cultural or economic exchange. Situated on the southwestern coast of India, the Kodava, Bunt, and Nair communities traded with Eurasian and African populations. It’s not hard to imagine that these trade relationships also involved exchanging customs that were passed down with each generation. However, Raghavan doesn’t rule out the possibility of a genetic link between southwestern coast communities and ancient Scythians or Greeks.

“It’s very rare to find sustained oral histories with such strong ties outside of the South Asian context, combined with such unique cultural practices,” she said. “One can always wonder what we would find if we sampled much more or had had access to more ancient DNA. There’s always a very small chance that maybe there was a non-local origin but admixing with local populations over time obscured that ancient link in the present-day descendants.”

Community engagement

One of Raghavan’s primary concerns with writing and publishing this paper was being sensitive to the communities and mindful of the impact that the results would have. Marginalized populations have a troubled history with human genetics researchers, many of whom extracted their data without consent or compensation. Indigenous communities, particularly in the Americas, have had their own genetic data weaponized against them in the past.

“Using genetics to ‘prove’ indigeneity of a community is a fallacy, but the way some studies are set up can further the misconception that this is ok to do,” Raghavan said. “In particular, discordance between genetic and anthropological definitions can have negative consequences for Indigenous people and how they are treated politically, threatening rights which had been based on their Indigenous identity.”

From the study’s inception, Raghavan and her lab prioritized outreach to the communities. This involved discussing complex scientific concepts with individuals at varying levels of experience with science and education.

“We started from scratch about what DNA is and what we are trying to do,” Raghavan said. “They may not understand all the technical details, but the priority is that they know that we've been unbiased in administering the study. And that takes trust.”

Raghavan and her co-authors built trust with members of Kodava, Bunt, and Nair communities in multiple ways. Their local research collaborators in India were valuable liaisons, familiar to the community and able to converse in their native languages. Additionally, some authors of this study themselves belong to the Kodava and Nair communities and were thus able to pitch the project at an annual convention for Kodava people in the US in 2018. Of course, not everyone the team approached was interested in participating, but many of them were supportive of the project.

“It’s easier for community members to trust their own when they come with a pitch,” Raghavan said. “And then we went there in 2019, to say ‘we have preliminary results, and we’re here to answer your questions.’ It’s important for them to see who they’re dealing with, and to know what is being done with their data.”

Even once their results were ready to publish, Raghavan and her co-authors shared the results with community members first, using platforms like Facebook, WhatsApp, and in person visits to circulate them. The results were summarized and described in lay language, with a full glossary for genetics terms and a guide on how to read the plots used in the actual manuscript. This document was also made far more accessible by local students in India, who translated the document into various local languages, and were compensated for their work by the lab.

Implications

The Kodava, Bunt, and Nair communities, like many other communities in South Asia, are highly endogamous, or marry only within the community. This can increase the risk of recessive genetic disorders. By comparing the genomes of community members, however, human genetics researchers could potentially identify genetic disease variants and target them for treatment.

Currently, the genomic data used for this study is protected, and cannot be used for further research without express permission from its participants. But Raghavan and her co-authors catalogued the unique variants they found in their analysis in hopes of motivating others to examine their medical relevance in future studies.

While consideration of disease-causing genetic variants is typical in human genetics studies, discussion of oral histories is not. Raghavan chose to include descriptions of each community’s self-identity, both to document them and to underscore their validity, even when they challenge a hypothesis supported by genetic methods.

“I'm very proud of the way that we brought this out,” she said. “And hopefully it's a way forward for using disparate disciplines together in a way where they’re not used to challenge each other's conclusions, rather can be brought together without being forced to be identical. Any discordances, such as the one we observed, can in fact motivate future anthropological and ethnographic investigations of the socio-cultural links that may have been the basis for some of the origin stories of these communities.”