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

Abstract

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.

Figure 1. More recent date of Denisovan than Neanderthal admixture

Average linkage disequilibrium (Lewontin’s D) as a function of distance in Oceanians for SNPs informative of Neanderthal (red) and Denisovan (blue) ancestry. The Denisova decay is slower implying a more recent date.

Figure 2. Variation in Denisovan ancestry proportion

(A) Proportion of the genome inferred to be Denisovan in ancestry in diverse non-Africans. The color scale is not linear to allow saturation of the high Denisova proportions in Oceania (bright red) and better visualization of the peak of Denisova proportion in South Asia. (B) Proportion of the genome confidently inferred to be Denisovan in ancestry in mainland Eurasians plotted against the rate of allele sharing of each samples with non-West Eurasians as measured by an f₄-statistic. The Denisovan ancestry estimates in South Asians are systematically above expectation (fitted trend line) (P=0.0013). See also Table S3.

Figure 3. Fine-scale maps of Denisovan and Neanderthal introgression

(A) Non-overlapping 100 kb windows that have non-zero inferred archaic ancestry in each of six populations (Denisova blue, Neanderthal red). In the innermost rings we plot deserts (windows >10 Mb). (B) Correlation of confidently inferred archaic ancestry (Neanderthal ancestry in six non-African populations as well as Denisovan ancestry in Oceanians) across populations in non-overlapping windows of size 100 kb, 1 Mb and 10 Mb. (C) We plot the median of the proportion of Denisovan and Neanderthal ancestry within quintiles of a B-statistic measuring intensity of linked selection (low B indicates the regions most affected by linked selection). See also Tables S6.