The shared genomic history of Middle- to Late-Holocene populations from the Southern Cone of South America

The Southern Cone represents the southernmost region of South America settled by humans. Although ancient genomes from southern Patagonia have been sequenced, genomes from the central Southern Cone (CSC) remain temporally and spatially sparse. Archaeology documents major cultural transformations during the Middle and Late Holocene, yet their relationship with demographic processes has been debated. We present genome-wide data from 52 individuals spanning 6,000 years, originating from four regions of the CSC in present-day Argentina and Uruguay: the central and southern Pampas, Northwest Patagonia, the Paraná River Delta and Lower Uruguay River, and the eastern lowlands of Uruguay. Genomic evidence from the Pampas reveals the presence of at least three distinct ancestries during the Middle Holocene. Although genetic contacts with southern Patagonian groups were sporadic, we identified the expansion of an ancestry of unknown geographic origin by 5,500 years ago (ya), which increased during the Late Holocene. This ancestry arrived in Northwest Patagonia by at least 600 ya and co-existed locally with a southern Andean genetic profile until colonial times. Genetic structure differentiates populations along the Paraná River Delta and Lower Uruguay River by 1,500 ya. Individuals from the eastern lowlands of Uruguay show genetic links with Sambaqui-associated populations from the southern coast of Brazil, suggesting the role of human dispersals in connecting tropical lowland cultural traditions. Our work documents the diffusion of genetically distinct groups across all studied regions and provides compelling evidence that large-scale human movements contributed to the remarkable cultural diversity of CSC populations during the Middle and Late Holocene.