Nuclear and mitochondrial DNA sequences from two Denisovan individuals

Abstract

Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.

Keywords: Denisovans; Neandertals; ancient DNA.

Fig. 1.

Occlusal surfaces of the Denisova 4 and Denisova 8 molars and third molars of a Neandertal and a present-day European.

Fig. 2.

Evolutionary relationships of Denisovan mtDNAs. (A) Bayesian tree relating the mtDNAs of three Denisovans, seven Neandertals, and five present-day humans. Posterior probabilities are indicated. A chimpanzee mtDNA was used to root the tree. (B) Numbers of differences between the two molar mtDNAs and the inferred common mtDNA ancestor of the three Denisovan mtDNAs. (C) Pairwise nucleotide differences among the Denisovans and Neandertals (Left) and among the Denisovans and 311 present-day human mtDNAs (Right).

Fig. 3.

Nuclear DNA divergence between Denisova 4 and Denisova 8 and the Denisovan genome. (A) DNA sequences from Denisova 4 and 8 were each compared with the genomes of Denisova 3 (3) and the inferred human–chimpanzee ancestor (25, 26). The differences from the human–chimpanzee ancestor common to the two Denisovans (a) as well as differences unique to each Denisovan are shown (b and c). Errors in the low-coverage Denisova genomes result in artificially long branches (c). Divergences of the molar genomes to Denisova 3 are therefore calculated as the percentage of all differences between Denisova 3 and the human–chimpanzee ancestor that are not shared with the molar genomes, b/(a + b) × 100. (B) Autosomal divergences of Denisova 4 and Denisova 8 to the Denisova 3 genome, the Neandertal genome, and 10 present-day human genomes calculated as in A. All estimates are based on DNA fragments from the two molars that carry putative deamination-induced C to T substitutions. Bars indicate 95% confidence intervals.