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Pubmed ID :16172508
Publication Date : //

The role of selection in the evolution of human mitochondrial genomes.


High mutation rate in mammalian mitochondrial DNA generates a highly divergent pool of alleles even within species that have dispersed and expanded in size recently. Phylogenetic analysis of 277 human mitochondrial genomes revealed a significant (P < 0.01) excess of rRNA and nonsynonymous base substitutions among hotspots of recurrent mutation. Most hotspots involved transitions from guanine to adenine that, with thymine-to-cytosine transitions, illustrate the asymmetric bias in codon usage at synonymous sites on the heavy-strand DNA. The mitochondrion-encoded tRNAThr varied significantly more than any other tRNA gene. Threonine and valine codons were involved in 259 of the 414 amino acid replacements observed. The ratio of nonsynonymous changes from and to threonine and valine differed significantly (P = 0.003) between populations with neutral (22/58) and populations with significantly negative Tajima's D values (70/76), independent of their geographic location. In contrast to a recent suggestion that the excess of nonsilent mutations is characteristic of Arctic populations, implying their role in cold adaptation, we demonstrate that the surplus of nonsynonymous mutations is a general feature of the young branches of the phylogenetic tree, affecting also those that are found only in Africa. We introduce a new calibration method of the mutation rate of synonymous transitions to estimate the coalescent times of mtDNA haplogroups.

Authors : Kivisild Toomas , Shen Peidong , Wall Dennis P , Do Bao , Sung Raphael , Davis Karen , Passarino Giuseppe , Underhill Peter A , Scharfe Curt , Torroni Antonio , Scozzari Rosaria , Modiano David , Coppa Alfredo , de Knijff Peter , Feldman Marcus , Cavalli-Sforza Luca L , Oefner Peter J ,

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