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.

[1]  T. Kivisild,et al.  Phylogeographic differentiation of mitochondrial DNA in Han Chinese. , 2002, American journal of human genetics.

[2]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[3]  A. Torroni,et al.  Classification of European mtDNAs from an analysis of three European populations. , 1996, Genetics.

[4]  Hans-Jürgen Bandelt,et al.  Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences. , 2003, American journal of human genetics.

[5]  D. Turnbull,et al.  Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups. , 2002, American journal of human genetics.

[6]  L. Excoffier,et al.  Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups. , 1995, American journal of human genetics.

[7]  Jonathan Scott Friedlaender,et al.  Expanding Southwest Pacific mitochondrial haplogroups P and Q. , 2005, Molecular biology and evolution.

[8]  Paul Mellars,et al.  Neanderthals and the modern human colonization of Europe , 2004, Nature.

[9]  S. Pääbo,et al.  Evidence for import of a lysyl-tRNA into marsupial mitochondria. , 2001, Molecular biology of the cell.

[10]  Alexei J Drummond,et al.  Time dependency of molecular rate estimates and systematic overestimation of recent divergence times. , 2005, Molecular biology and evolution.

[11]  M. Nei,et al.  Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. , 1993, Molecular biology and evolution.

[12]  T. White,et al.  Stratigraphic, chronological and behavioural contexts of Pleistocene Homo sapiens from Middle Awash, Ethiopia , 2003, Nature.

[13]  M. Lehtonen,et al.  Phylogenetic network for European mtDNA. , 2001, American journal of human genetics.

[14]  H. Bandelt,et al.  Origin and evolution of Native American mtDNA variation: a reappraisal. , 1996, American journal of human genetics.

[15]  L. Cavalli-Sforza,et al.  Ethnic variation in Hpa 1 endonuclease cleavage patterns of human mitochondrial DNA. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Aquadro,et al.  Human mitochondrial DNA variation and evolution: analysis of nucleotide sequences from seven individuals. , 1983, Genetics.

[17]  M. Stoneking,et al.  Nonneutral mitochondrial DNA variation in humans and chimpanzees. , 1996, Genetics.

[18]  C. Stringer,et al.  Genetic and fossil evidence for the origin of modern humans. , 1988, Science.

[19]  Á. Carracedo,et al.  The making of the African mtDNA landscape. , 2002, American journal of human genetics.

[20]  Q. Kong,et al.  Phylogeographic analysis of mitochondrial DNA haplogroup F2 in China reveals T12338C in the initiation codon of the ND5 gene not to be pathogenic , 2004, Journal of Human Genetics.

[21]  C. Tyler-Smith,et al.  Where west meets east: the complex mtDNA landscape of the southwest and Central Asian corridor. , 2004, American journal of human genetics.

[22]  M. Zeviani,et al.  The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. , 2004, American journal of human genetics.

[23]  W. Brown,et al.  Polymorphic sites and the mechanism of evolution in human mitochondrial DNA. , 1984, Genetics.

[24]  R. Nielsen,et al.  Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. , 2002, Molecular biology and evolution.

[25]  T. White,et al.  Pleistocene Homo sapiens from Middle Awash, Ethiopia , 2003, Nature.

[26]  H. Cann,et al.  Maternal inheritance of human mitochondrial DNA. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[27]  K. Majamaa,et al.  Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J. , 2003, Molecular biology and evolution.

[28]  J. Fleagle,et al.  Stratigraphic placement and age of modern humans from Kibish, Ethiopia , 2005, Nature.

[29]  T. Ozawa,et al.  Strand asymmetry in human mitochondrial DNA mutations. , 1994, Genomics.

[30]  P. Forster,et al.  Phylogenetic star contraction applied to Asian and Papuan mtDNA evolution. , 2001, Molecular biology and evolution.

[31]  Li Jin,et al.  Y chromosome sequence variation and the history of human populations , 2000, Nature Genetics.

[32]  U. Gyllensten,et al.  Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines. , 2003, Genome research.

[33]  R Giegé,et al.  Search for characteristic structural features of mammalian mitochondrial tRNAs. , 2000, RNA.

[34]  Hidetoshi Shimodaira,et al.  Mitochondrial genome variation in eastern Asia and the peopling of Japan. , 2004, Genome research.

[35]  J V Neel,et al.  Asian affinities and continental radiation of the four founding Native American mtDNAs. , 1993, American journal of human genetics.

[36]  H. Bandelt,et al.  Median-joining networks for inferring intraspecific phylogenies. , 1999, Molecular biology and evolution.

[37]  D. Turnbull,et al.  Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA , 1999, Nature Genetics.

[38]  Marty C. Brandon,et al.  Natural selection shaped regional mtDNA variation in humans , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. Pääbo,et al.  Mitochondrial genome variation and the origin of modern humans , 2000, Nature.

[40]  N. Léger,et al.  Evidence for multiple reversals of asymmetric mutational constraints during the evolution of the mitochondrial genome of metazoa, and consequences for phylogenetic inferences. , 2005, Systematic biology.

[41]  D. Turnbull,et al.  Comparative genomics and the evolution of human mitochondrial DNA: assessing the effects of selection. , 2004, American journal of human genetics.

[42]  Marty C. Brandon,et al.  Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA , 2004, Science.

[43]  M. Feldman,et al.  HUMAN MUTATION 24:248^260 (2004) RESEARCH ARTICLE Reconstruction of Patrilineages and Matrilineages of Samaritans and Other Israeli Populations From Y-Chromosome and Mitochondrial DNA Sequence Variation , 2022 .

[44]  A. Torroni,et al.  Phylogeography of the human mitochondrial haplogroup L3e: a snapshot of African prehistory and Atlantic slave trade , 2001, Annals of human genetics.

[45]  H. Bandelt,et al.  Mitochondrial footprints of human expansions in Africa. , 1997, American journal of human genetics.

[46]  Ziheng Yang,et al.  Likelihood and Bayes estimation of ancestral population sizes in hominoids using data from multiple loci. , 2002, Genetics.

[47]  I. Rogozin,et al.  Mutagenesis by Transient Misalignment in the Human Mitochondrial DNA Control Region , 2004, Annals of human genetics.

[48]  C. Groves,et al.  Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence. , 1998, Molecular phylogenetics and evolution.

[49]  L. Excoffier,et al.  Intra-deme molecular diversity in spatially expanding populations. , 2003, Molecular biology and evolution.

[50]  A. Torroni,et al.  The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs. , 1999, American journal of human genetics.

[51]  H. Bandelt,et al.  mtDNA variation among Greenland Eskimos: the edge of the Beringian expansion. , 2000, American journal of human genetics.

[52]  David Penny,et al.  Evolutionary biology: Relativity for molecular clocks , 2005, Nature.

[53]  R. Villems,et al.  Ethiopian mitochondrial DNA heritage: tracking gene flow across and around the gate of tears. , 2004, American journal of human genetics.

[54]  Robert W. Taylor,et al.  Assigning pathogenicity to mitochondrial tRNA mutations: when "definitely maybe" is not good enough. , 2004, Trends in genetics : TIG.

[55]  U. Gyllensten,et al.  Analysis of the complete human mtDNA genome: methodology and inferences for human evolution. , 2001, The Journal of heredity.

[56]  Hans-Jürgen Bandelt,et al.  Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia. , 2004, American journal of human genetics.

[57]  G. Valle,et al.  Do the four clades of the mtDNA haplogroup L2 evolve at different rates? , 2001, American journal of human genetics.

[58]  K. Majamaa,et al.  Phylogenetic network and physicochemical properties of nonsynonymous mutations in the protein-coding genes of human mitochondrial DNA. , 2003, Molecular biology and evolution.

[59]  Hans-Jürgen Bandelt,et al.  The emerging limbs and twigs of the East Asian mtDNA tree. , 2002, Molecular biology and evolution.