Evaluating purifying selection in the mitochondrial DNA of various mammalian species

PLoS One. 2013;8(3):e58993. doi: 10.1371/journal.pone.0058993. Epub 2013 Mar 22.

Abstract

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. Here, by using this additional information, we show that purifying selection undoubtedly acts upon the mtDNA of other mammalian species/genera, namely Bos sp., Canis lupus, Mus musculus, Orcinus orca, Pan sp. and Sus scrofa. The effects of purifying selection were comparable in all species, leading to a significant major proportion of nonsynonymous variants with higher pathogenicity scores in the younger branches of the tree. We also derive recalibrated mutation rates for age estimates of ancestors of these various species and proposed a correction curve in order to take into account the effects of selection. Understanding this selection is fundamental to evolutionary studies and to the identification of deleterious mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • DNA, Mitochondrial / genetics*
  • Dogs
  • Mammals
  • Mice
  • Phylogeny
  • Sus scrofa
  • Whale, Killer

Substances

  • DNA, Mitochondrial

Grants and funding

FCT, the Portuguese Foundation for Science and Technology, supported this work through the personal grant to PS (SFRH/BPD/64233/2009) and TR (under the project PTDC/CS-ANT/113832/2009). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT (www.fct.pt). LP and PS had a mobility grant from The Luso-American Development Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.