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.
Kivisild
Toomas
T
Department of Human and Clinical Genetics, Leiden University Medical Center, 2333 AL Leiden, The Netherlands. tkivisil@ebc.ee
Shen
Peidong
P
Wall
Dennis P
DP
Do
Bao
B
Sung
Raphael
R
Davis
Karen
K
Passarino
Giuseppe
G
Underhill
Peter A
PA
Scharfe
Curt
C
Torroni
Antonio
A
Scozzari
Rosaria
R
Modiano
David
D
Coppa
Alfredo
A
de Knijff
Peter
P
Feldman
Marcus
M
Cavalli-Sforza
Luca L
LL
Oefner
Peter J
PJ
D019943:Amino Acid Substitution; D020029:Base Pairing; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D012335:RNA, Ribosomal / Q000235:genetics; D012641:Selection, Genetic
D003062:Codon; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal