The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans

Highlights

• Denisovan admixture into modern humans occurred after Neanderthal admixture

• There is more Denisovan ancestry in South Asians than expected from current models

• Denisovan ancestry has been subject to positive and negative selection after admixture

• Male infertility most likely occurred after modern human interbreeding with Denisovans

Summary

Some present-day humans derive up to ∼5% [1] of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals [2]. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry [3]. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10⁻⁷ to 3.2 × 10⁻⁷ for Denisovan and 2.2 × 10⁻³ to 2.9 × 10⁻³ for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.