New study reveals 50,000 years of India's genetic history. Here's how that could help treat disease
'This lack of representation leads to limited benefits of genetic findings to the Indian population,' said Priya Moorjani, a UC Berkeley assistant professor of molecular and cell biology.
A new paper she and others wrote helps change that.
Moorjani is the senior author of a study published Thursday that delivers the most comprehensive snapshot to date of genetic diversity in India. The research provides new insights into 50,000 years of complex South Asian evolutionary history and clues about why some genetic conditions are particularly prevalent in specific communities.
The researchers analyzed genomes for over 2,700 individuals across India. Most of this data was generated as part of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia. The dataset is representative of the population diversity in India, including people born in 23 states and territories and speaking 26 languages.
Because genetic material is inherited, the DNA sequences provide 'information about our ancestors, even going back thousands and millions of years ago,' Moorjani said.
The researchers found that the majority of the genetic variation in present-day Indians was explained by a major migration of humans out of Africa about 50,000 years ago.
These migrating humans then interbred with now extinct Neanderthals and Denisovans, another species of early hominid more evident in the genetic record than in the fossil record. These slightly hybridized humans then spread throughout Europe and Asia.
Indians have about 1% to 2% of their ancestry from Neanderthals, similar to individuals from Europe and the Americas, according to the study. They have 0.1% Denisovan ancestry, similar to Americans and East Asians. Since Neanderthals and Denisovans were already genetically adapted to living outside of Africa, these ancient genes helped migrating humans adapt to new climates, Moorjani explained.
This genetic material can have unexpected impacts today, said Elise Kerdoncuff, a former UC Berkeley postdoctoral fellow and one of two lead authors of the paper. For example, genetic material inherited from Neanderthals is linked to increased risk of respiratory failure from COVID-19.
One of the 'most striking findings' from the new study was that there's larger variation in Neanderthal ancestry in Indians than in other populations, Moorjani said: 'Because Indians are so much more diverse, we find that we can reconstruct almost half of the Neanderthal genome. And similarly, we can reconstruct a third of the Denisovan genome.'
While the migration 50,000 years ago forms the backbone of the Indian genetic makeup, that was just the first major wave. The researchers found that about 10,000 years ago, India received a second infusion of genetic material when existing South Asian hunter-gatherers mixed with migrating farmers from what is now Iran. A third major contribution took place about 3,500 years ago, Kerdoncuff said, when pastoralists from the Central Asian steppe arrived in North India.
Genetic impacts on health
Starting between 3,000 and 5,000 years ago, there has been a cultural shift toward endogamy, or within-community marriages. 'What this does is, it increases the chance of inheriting the same piece of DNA from both your parents,' Moorjani explained, a phenomenon called 'homozygosity.'
When that happens, people can get 'recessive diseases' — when an individual inherits two copies of a mutated gene. The researchers found that 15 individuals analyzed in the study had a mutation in their genes for BCHE, an enzyme that when mutated causes a severe adverse reaction to certain anesthetics, Kerdoncuff said.
Improved understanding of genetic variation in Indian populations could help with screening for genetic disorders or developing targeted drugs for different populations. This also applies for South Asian communities outside of India, like in California.
The researchers are continuing to collect, sequence and analyze genetic data as part of the Longitudinal Aging Study in India.
The work was funded by the U.S. National Institutes of Health.
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