From North Asia to South America: Tracing the longest human migration through genomic sequencing.

Genome sequencing of 1537 individuals from 139 ethnic groups reveals the genetic characteristics of understudied populations in North Asia and South America. Our analysis demonstrates that West Siberian ancestry, represented by the Kets and Nenets, contributed to the genetic ancestry of most Siberian populations. West Beringians, including the Koryaks, Inuit, and Luoravetlans, exhibit genetic adaptation to Arctic climate, including medically relevant variants. In South America, early migrants split into four groups—Amazonians, Andeans, Chaco Amerindians, and Patagonians—~13,900 years ago. Their longest migration led to population decline, whereas settlement in South America's diverse environments caused instant spatial isolation, reducing genetic and immunogenic diversity. These findings highlight how population history and environmental pressures shaped the genetic architecture of human populations across North Asia and South America. Editor's summary: From our origins in Africa, humans have migrated and settled across the world. Perhaps none of these migrations has been the subject of as much debate as the expansion into and throughout the Americas. Gusareva et al. used 1477 whole-genome sequenced samples from 139 populations in South America and Northeast Eurasia to shed light on the population history of Native Americans. Collected as a part of the GenomeAsia 100K consortium, analysis of these data showed that there are four main ancestral lineages that contributed to modern South Americans. These lineages diverged from each other between 10,000 and 14,000 years ago, and this analysis reveals more details of the population history dynamics in these groups. —Corinne Simonti INTRODUCTION: During the late Pleistocene, humans expanded across Eurasia and eventually migrated to the Americas. Those who reached Patagonia, at the southern tip of South America, completed the longest migration out of Africa. RATIONALE: The extent of basal divergences, admixture, and degrees of isolation among Indigenous North Eurasian and Native South American populations remain debated, with most insights derived from genome-wide genotyping data. This study aims to deepen our understanding of the ancient dynamics that shaped contemporary populations in North Eurasia and the Americas. By using large-scale whole-genome sequencing of 1537 individuals from 139 ethnic groups in these regions, we examined population structures, elucidated prehistoric migrations, and explored the influence of past environmental factors on the diversification of human populations. RESULTS: Advances in large-scale genomic sequencing have considerably enhanced our understanding of the genetic ancestry of human populations across North Eurasia and South America. Our analysis reveals that all contemporary Siberians, as well as some Northeast Europeans and Central Asians, share ancestry with the West Siberian groups, represented by the Kets and Nenets. Their ancestors were widespread across Siberia 10,000 years ago (ya), but now these groups face population decline by 73.6% and are becoming a minority. The populations of west Beringia, including the Koryaks, Inuit, and Luoravetlans, are the most genetically distinct from other Siberians. These groups have adapted to Arctic conditions with genetic variations related to lipid metabolism, thermogenesis, sensory perception, and the regulation of reproductive and immune functions. We were not able to identify a specific Siberian group as the direct ancestors of Native Americans owing to deep divergence and limited genetic continuity. However, west Beringian populations remain closely related to Native Americans. Koryaks and Inuit show 5 and 28% Native American ancestry, respectively, owing to gene flow between 700 and 5100 ya. We estimated the split time of Native South Americas into Amazonians, Andeans, Chaco Amerindians, and Patagonians to have occurred 13,900 to 10,000 ya. Migration and settlement across the continent led to population isolations due to geographic boundaries and a reduction in their genetic diversity, particularly affecting immune genes, such as the human leukocyte antigen (HLA) genes. Over the past 10,000 years, all four Native South American lineages have experienced population declines ranging from 38 to 80%. This dramatic decline, combined with the loss of traditional lifestyles, cultural practices, and languages, has pushed some Indigenous communities, such as the Kawésqar, to the brink of extinction. CONCLUSION: The migration to an uninhabited continent of South America through the narrow Isthmus of Panama resulted in a founder effect among Native South Americans, leading to reduced genetic diversity compared with that of Indigenous populations of North Eurasia. Over 13,900 years, geographic barriers within the continent further isolated Indigenous groups, subsequently reducing genetic diversity. These groups faced a profound challenge with the arrival of European colonists in the 1600s, who introduced new adversities that threatened their long-standing endurance. Genetic ancestry and nucleotide diversity.: Colors represent genetic ancestries estimated by whole-genome sequencing data of contemporary human populations. Countries having no data remained empty. Circle size indicates the average nucleotide diversity of each population. [ABSTRACT FROM AUTHOR]