Evaluating purifying selection in the mitochondrial DNA of various mammalian species.

Mitochondrial DNA (mtDNA), the circular DNA molecule inside the mitochondria of all eukaryotic cells, has been shown to be under the effect of purifying selection in several species. Traditional testing of purifying selection has been based simply on ratios of nonsynonymous to synonymous mutations, without considering the relative age of each mutation, which can be determined by phylogenetic analysis of this non-recombining molecule. The incorporation of a mutation time-ordering from phylogeny and of predicted pathogenicity scores for nonsynonymous mutations allow a quantitative evaluation of the effects of purifying selection in human mtDNA.

Ancient voyaging and Polynesian origins.

The "Polynesian motif" defines a lineage of human mtDNA that is restricted to Austronesian-speaking populations and is almost fixed in Polynesians. It is widely thought to support a rapid dispersal of maternal lineages from Taiwan ~4000 years ago (4 ka), but the chronological resolution of existing control-region data is poor, and an East Indonesian origin has also been proposed. By analyzing 157 complete mtDNA genomes, we show that the motif itself most likely originated >6 ka in the vicinity of the Bismarck Archipelago, and its immediate ancestor is >8 ka old and virtually restricted to Near Oceania.

Correcting for purifying selection: an improved human mitochondrial molecular clock.

There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees.