Distinct patterns of mitochondrial genome diversity in bonobos (Pan paniscus) and humans

Abstract

Background: We have analyzed the complete mitochondrial genomes of 22 Pan paniscus (bonobo, pygmy chimpanzee) individuals to assess the detailed mitochondrial DNA (mtDNA) phylogeny of this close relative of Homo sapiens.

Results: We identified three major clades among bonobos that separated approximately 540,000 years ago, as suggested by Bayesian analysis. Incidentally, we discovered that the current reference sequence for bonobo likely is a hybrid of the mitochondrial genomes of two distant individuals. When comparing spectra of polymorphic mtDNA sites in bonobos and humans, we observed two major differences: (i) Of all 31 bonobo mtDNA homoplasies, i.e. nucleotide changes that occurred independently on separate branches of the phylogenetic tree, 13 were not homoplasic in humans. This indicates that at least a part of the unstable sites of the mitochondrial genome is species-specific and difficult to be explained on the basis of a mutational hotspot concept. (ii) A comparison of the ratios of non-synonymous to synonymous changes (dN/dS) among polymorphic positions in bonobos and in 4902 Homo sapiens mitochondrial genomes revealed a remarkable difference in the strength of purifying selection in the mitochondrial genes of the F0F1-ATPase complex. While in bonobos this complex showed a similar low value as complexes I and IV, human haplogroups displayed 2.2 to 7.6 times increased dN/dS ratios when compared to bonobos.

Conclusions: Some variants of mitochondrially encoded subunits of the ATPase complex in humans very likely decrease the efficiency of energy conversion leading to production of extra heat. Thus, we hypothesize that the species-specific release of evolutionary constraints for the mitochondrial genes of the proton-translocating ATPase is a consequence of altered heat homeostasis in modern humans.

Figure 1

Pairwise nucleotide differences of complete mitochondrial genomes. (A) 22 Pan paniscus sequences. (B) Homo sapiens sequences including 21 selected contemporary sequences representing all major human haplogroups and 6 Neandertal sequences [4,5]. Rightmost bars indicate pairwise differences between modern humans and Neandertals.

Figure 2

Neighbor-joining tree of complete Pan paniscus mitochondrial genomes with Pan troglodytes as outgroup. Bootstrap values are shown at the branches. Scale bar, evolutionary distance (substitutions per nucleotide position).

Figure 3

Ratios of non-synonymous to synonymous mutations in mitochondrial protein coding genes. The mitochondrial genes were pooled according to oxidative phosphorylation (OXPHOS) complexes: complex I (MT-ND1, MT-ND2, MT-ND3, MT-ND4L, MT-ND4, MT-ND5, MT-ND6), complex III (MT-CYB), complex IV (MT-CO1, MT-CO2, MT-CO3), and complex V (MT-ATP8, MT-ATP6). Numbers of individuals are shown in brackets; numbers above the bars indicate the total number of polymorphic position for the specific group of protein coding genes. (A) d_N/d_S ratios of within-group polymorphic sites in Pan paniscus and diverse human haplogroups, including Neandertals. Note that d_N/d_S ratio of within-species polymorphisms is also referred to as θ_N/θ_S in other studies. Statistical significance is indicated by stars (*, P < 0.05; **, P < 0.01; ***, P < 0.005) (B) d_N/d_S ratios of stable species-specific mutations in gorillas, chimpanzees, bonobos, and 21 human sequences representing all major haplogroups. The scheme on the left shows an unrooted tree of hominids. Filled circles represent species; nucleotide differences were calculated from the theoretical branching point indicated by star.