Effects of purifying and adaptive selection on regional variation in human mtDNA.
A phylogenetic analysis of 1125 global human mitochondrial DNA (mtDNA) sequences permitted positioning of all nucleotide substitutions according to their order of occurrence. The relative frequency and amino acid conservation of internal branch replacement mutations was found to increase from tropical Africa to temperate Europe and arctic northeastern Siberia. Particularly highly conserved amino acid substitutions were found at the roots of multiple mtDNA lineages from higher latitudes. These same lineages correlate with increased propensity for energy deficiency diseases as well as longevity. Thus, specific mtDNA replacement mutations permitted our ancestors to adapt to more northern climates, and these same variants are influencing our health today.
Ruiz-Pesini
Eduardo
E
Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, CA 92697-3940, USA.
Mishmar
Dan
D
Brandon
Martin
M
Procaccio
Vincent
V
Wallace
Douglas C
DC
D000222:Adaptation, Physiological; D000349:Africa; D001110:Arctic Regions; D001208:Asia; D002980:Climate; D003081:Cold Climate; D017124:Conserved Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D004641:Emigration and Immigration; D004734:Energy Metabolism; D005060:Europe; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008136:Longevity; D008659:Metabolic Diseases / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics; D010641:Phenotype; D010802:Phylogeny; D044469:Racial Groups / Q000235:genetics; D012641:Selection, Genetic; D012800:Siberia
D004272:DNA, Mitochondrial