A high-coverage Neandertal genome from Vindija Cave in Croatia

Abstract

To date, the only Neandertal genome that has been sequenced to high quality is from an individual found in Southern Siberia. We sequenced the genome of a female Neandertal from ~50,000 years ago from Vindija Cave, Croatia, to ~30-fold genomic coverage. She carried 1.6 differences per 10,000 base pairs between the two copies of her genome, fewer than present-day humans, suggesting that Neandertal populations were of small size. Our analyses indicate that she was more closely related to the Neandertals that mixed with the ancestors of present-day humans living outside of sub-Saharan Africa than the previously sequenced Neandertal from Siberia, allowing 10 to 20% more Neandertal DNA to be identified in present-day humans, including variants involved in low-density lipoprotein cholesterol concentrations, schizophrenia, and other diseases.

Fig. 1.. Heterozygosity and inbreeding in the Vindija Neandertal.

(A) Distribution of heterozygosity over all autosomes in the three archaic hominins, 12 Non-Africans and 3 Africans. Each dot represents the heterozygosity measured for one autosome. The center bar indicates the mean heterozygosity across the autosomal genome. (B) Genome covered by shorter (2.5–10cM, red) and longer (>10cM, yellow) runs of homozygosity in the three archaic hominins.

Fig. 2.. Approximate ages of specimens and population split times.

Age estimates for the genomes estimated from branch shortening, i.e. the absence of mutations in the archaic genomes, are indicated by dashed lines. Population split time estimates are indicated by dashed lines. The majority of Neandertal DNA in present-day people comes from a population that split from the branch indicated in red. All reported ages assume a human-chimpanzee divergence of 13 million years. Numbers show ranges over point estimates (split times), or ranges over different data filters (branch shortening).

Fig. 3.. Allele sharing between archaic and modern humans.

(A) Derived allele-sharing in percent of 19 African populations with the Altai and Denisovan, and Vindija and Denisovan genomes, respectively. (B) Sharing of derived alleles in each of the 19 African populations with the Vindija and Altai genomes. (C) Allele sharing of Neandertals with non-Africans and Africans. Points show derived allele sharing in percent for all pairwise comparisons between non-Africans (OAA: French, Sardinian, Han, Dai, Karitiana, Mixe, Australian, Papuan) and Africans (AFR: San, Mbuti, Yoruba). Mezmaiskaya 1 data were restricted to sequences showing evidence of deamination to reduce the influence of present-day human DNA contamination. Lines show two standard errors from the mean in all plots.

Fig. 4.. Estimates of fraction of Neandertal DNA for present-day populations.

(A) Colors indicate Neandertal ancestry estimates (20). Oceanian populations show high estimates due to Denisovan ancestry that is difficult to distinguish from Neandertal ancestry. (B) Amount of Neandertal sequence in present-day Europeans, South Asians and East Asians (20).