The DNA of India: How Neanderthal genes, ancient migrations, and caste shaped a billion people

The DNA is a thick, ancient book filled with stories of our ancestors, not just our parents or grandparents, but people who lived thousands of years ago. Scientists have now read this book for over 2,700 individuals from India and compared it with the DNA from people around the world, both living and ancient. This study, the largest of its kind in India, reveals a 50,000-year-old tale of migrations, mixing, and cultural practices that shaped the genetic diversity we see today.

The research, conducted by experts from the University of California, Berkeley, AIIMS Delhi, the University of Southern California, and the University of Michigan, was published in the prestigious journal Cell. It answers key questions: When did humans first reach India from Africa? How much of our DNA comes from extinct human relatives like Neanderthals? What role did ancient Iranian farmers play in India’s agricultural revolution? And why do some Indian communities have a higher risk of certain genetic diseases?

Our ancient cousins: How Neanderthals and Denisovans shaped Indian genes

Long before our ancestors built cities and river valley civilisations, they shared Earth with other human-like species, the Neanderthals in Europe and West Asia and the Denisovans in Siberia and Southeast Asia. These were not our direct ancestors but rather distant cousins who had separated from our family tree approximately 5 lakh years ago. When our Homo Sapiens ancestors migrated out of Africa around 80,000 years ago, they encountered these groups and intermarried with them. This ancient mixing means even today, all Indians carry about 1.43% (ranging from 1.26 to 1.65%) Neanderthal DNA in their genes, similar to Europeans. We also have a small but significant 0.1% Denisovan ancestry, similar to that of East Asians.

The study found that India holds the world's most diverse collection of Neanderthal genes, indicating that these ancient DNA fragments survived better in this region than anywhere else.

“This is because of the complex history of South Asians,” Priya Moorjani, a senior author of the paper and a UC Berkeley assistant professor of molecular and cell biology, explained. “They've had multiple mixture events over the past 10,000 years, followed by strong bottlenecks in many groups. Together, that leads to a very complex mosaic of different ancestries, such that when you compare the Neanderthal segments in two individuals, they're often not shared.”

And it is not just random junk DNA; some of these genes actually have an impact on us. For example, Neanderthal DNA influences our immunity (explaining why some individuals experience severe COVID-19), skin colour, and even how we digest food. The Denisovan genes helped Tibetans survive high altitudes, showing how this ancient mixing actually impacted later generations.

A key question in understanding peopeling of India is determining when modern humans first arrived from Africa. While archaeological evidence suggests a human presence in India both before and after the massive Toba eruption (~74,000 years ago), this genetic study reveals that most modern Indians primarily trace their ancestry to a later African migration wave around 50,000 years ago.

"Potentially, there were earlier waves out of Africa to India, but it's likely that those groups either did not survive or left little genetic impact on today's populations," said Elise Kerdoncuff, a former UC Berkeley postdoctoral fellow and one of two lead authors of the paper.

The Iranian farmers: The agricultural revolution in India

Around 8,000–9,000 years ago, a significant shift occurred in India, marking the transition from a hunter-gatherer to a farming-based society. Archaeological sites like Mehrgarh (Pakistan) show evidence of early wheat and barley cultivation, crops originally domesticated in the Fertile Crescent (modern-day Iraq and Iran). But who brought farming to India?

By comparing ancient DNA from Neolithic Iranian farmers (4,000–3,500 BCE) with modern Indian genomes, researchers traced the source of this ancestry to Sarazm, Tajikistan —a key trade hub connected to the Indus Valley Civilisation. Genetic evidence matches archaeological findings; shell bangles, originating from the Indian Ocean or the Arabian Sea, found at Indian Neolithic sites such as Shahi-Tump, Makran, and Surkotada in Gujarat, were also discovered in Sarazm, indicating early trade links.

Another significant genetic influence originated from the Eurasian Steppe, a vast grassland that stretches from Ukraine to Mongolia. Around 4,000 years ago, nomadic herders from this region migrated into India. In India, their genetic impact is strongest in North and Northwest populations (0–45% Steppe ancestry), decreasing towards the South. Together, these three groups — hunter-gatherers, farmers, and pastoralists — contributed to the genetic variation now found throughout India.

The genetic consequences of endogamy in India

Following these admixtures, particularly with the arrival of nomadic herders around 4000 years ago, India experienced a significant demographic shift toward endogamy, the practice of marrying within specific castes, clans, or tribes.

This engendered a rigid hierarchical system based on the oppressive practice of caste-based endogamy. This dehumanising system not only institutionalised oppression, violent social control and economic exploitation but also locked populations into genetic isolation, resulting in damaging health impacts persisting generations later.

A chilling parallel can be seen in Elisabeth Nietzsche (sister of philosopher Friedrich Nietzsche) 's 'New Germany' (Nueva Germania) experiment in 1900s Paraguay, where a small, isolated community of so-called 'racially pure' Germans intermarried for generations within the isolated community, much akin to marrying within the caste, resulting in devastating genetic disorders like deafness, dwarfism, and cognitive impairments.

In India, the caste system's enforcement of marital segregation created similar but far more widespread genetic injury. When populations are forcibly confined to narrow gene pools through social oppression, the biological consequences are inevitable. When small founder populations expand while maintaining strict marriage boundaries, it leads to high rates of homozygosity, where children inherit identical deleterious gene copies from both parents. This dramatically increases the risk of recessive genetic disorders.

"With these founder events, members of a group become much more related because they're exchanging genes just within the community," Priya Moorjani, a senior author of the paper and a UC Berkeley assistant professor of molecular and cell biology, said. "So if a deleterious variant is present in the community, it can drift to high frequency in the population because there's less variation."

This study reveals alarming statistics: over 51% of Indians have at least one third-degree cousin or closer relative in their ancestry, compared to just 8.8% of Europeans. Practices such as gotra marriage have not helped; the thousand years of endogamy have made others in the caste group nearly third-degree cousins. Indians have elevated levels of homozygosity, with an average range across regions of ∼12 to 56 centiMorgans of homozygous DNA per individual, which is two to nine times higher than that of East Asians and Europeans. The effects are particularly pronounced in South India, where genetic analysis reveals 56 cM of homozygous DNA, compared to 19 cM in North India, matching with the higher rates of consanguineous marriage in South as compared to North Inia.

These practices have made certain genetic disorders shockingly prevalent in specific Indian communities. For instance, the L307P mutation, which causes butyrylcholinesterase gene that causes muscle paralysis and other severe reactions to anaesthetics like vivarium, is sporadic globally but frequently appears in some Indian caste groups. Similarly, mutations linked to blood disorders, metabolic diseases, and even dementia occur at rates 10 to 100 times higher in certain endogamous Indian groups than in other populations worldwide.

India's genetic tapestry: Ancient roots and modern impacts

This groundbreaking study traces India's rich genetic history, from ancient human migrations to interbreeding with now-extinct species, such as Neanderthals. Our DNA reveals how diverse populations intermixed over millennia but also shows how centuries of caste-based endogamy created distinct genetic patterns that continue to influence health outcomes today.

"These findings fill a critical gap and reshape our understanding of how ancient migrations, archaic admixture and social structures, like endogamy, have shaped the Indian genetic variation and risk of diseases, and will help inform precision health strategies in India," said Priya Moorjani.

The research team analysed genomes of 2,762 individuals from across India's linguistic, ethnic and geographic spectrum, drawn from the LASI-DAD study (Longitudinal Aging Study in India-Diagnostic Assessment of Dementia). This ambitious project has collected 70,000 Indian genomes, with detailed sequencing planned to study aging-related diseases through epigenetics, metabolomics and proteomics.

As the authors emphasise: "The unique genetic structure of Indians underscores the importance of incorporating ancestry and homozygosity in future medical and functional genomics research."