Copyright © 2008 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 82, Issue 4, 895-902, 28 March 2008
doi:10.1016/j.ajhg.2008.01.019
Article
A Bayesian Evaluation of Human Mitochondrial Substitution Rates
Phillip Endicott1 and Simon Y.W. Ho1, 2, 
, 
1 Department of Zoology, University of Oxford, Oxford OX1 3PS, UK
Corresponding author2 Present address: Centre for Macroevolution and Macroecology, School of Botany and Zoology, Australian National University, Canberra ACT 0200, Australia.
Abstract
Accurate estimates of mitochondrial substitution rates are central to molecular studies of human evolution, but meaningful comparisons of published studies are problematic because of the wide range of methodologies and data sets employed. These differences are nowhere more pronounced than among rates estimated from phylogenies, genealogies, and pedigrees. By using a data set comprising mitochondrial genomes from 177 humans, we estimate substitution rates for various data partitions by using Bayesian phylogenetic analysis with a relaxed molecular clock. We compare the effect of multiple internal calibrations with the customary human-chimpanzee split. The analyses reveal wide variation among estimated substitution rates and divergence times made with different partitions and calibrations, with evidence of substitutional saturation, natural selection, and significant rate heterogeneity among lineages and among sites. Collectively, the results support dates for migration out of Africa and the common mitochondrial ancestor of humans that are considerably more recent than most previous estimates. Our results also demonstrate that human mitochondrial genomes exhibit a number of molecular evolutionary complexities that necessitate the use of sophisticated analytical models for genetic analyses.
Article Information
PubMed
Related Articles
- mtDNA Variation in the South African Kung and Khwe—and Their...mtDNA Variation in the South African Kung and Khwe—and Their Genetic Relationships to Other African Populations
The American Journal of Human Genetics, Volume 66, Issue 4, 1 April 2000, Pages 1362-1383
Yu-Sheng Chen, Antonel Olckers, Theodore G. Schurr, Andreas M. Kogelnik, Kirsi Huoponen and Douglas C. Wallace
AbstractThe mtDNA variation of 74 Khoisan-speaking individuals (Kung and Khwe) from Schmidtsdrift, in the Northern Cape Province of South Africa, was examined by high-resolution RFLP analysis and control region (CR) sequencing. The resulting data were combined with published RFLP haplotype and CR sequence data from sub-Saharan African populations and then were subjected to phylogenetic analysis to deduce the evolutionary relationships among them. More than 77% of the Kung and Khwe mtDNA samples were found to belong to the major mtDNA lineage, macrohaplogroup L* (defined by a HpaI site at nucleotide position 3592), which is prevalent in sub-Saharan African populations. Additional sets of RFLPs subdivided macrohaplogroup L* into two extended haplogroups—L1 and L2—both of which appeared in the Kung and Khwe. Besides revealing the significant substructure of macrohaplogroup L* in African populations, these data showed that the Biaka Pygmies have one of the most ancient RFLP sublineages observed in African mtDNA and, thus, that they could represent one of the oldest human populations. In addition, the Kung exhibited a set of related haplotypes that were positioned closest to the root of the human mtDNA phylogeny, suggesting that they, too, represent one of the most ancient African populations. Comparison of Kung and Khwe CR sequences with those from other African populations confirmed the genetic association of the Kung with other Khoisan-speaking peoples, whereas the Khwe were more closely linked to non–Khoisan-speaking (Bantu) populations. Finally, the overall sequence divergence of 214 African RFLP haplotypes defined in both this and an earlier study was 0.364%, giving an estimated age, for all African mtDNAs, of 125,500–165,500 years before the present, a date that is concordant with all previous estimates derived from mtDNA and other genetic data, for the time of origin of modern humans in Africa.
Abstract | | - The Genomic Record of Humankind's Evolutionary RootsThe Genomic Record of Humankind's Evolutionary Roots
The American Journal of Human Genetics, Volume 64, Issue 1, 1 January 1999, Pages 31-39
Morris Goodman
| - A Cascade of Complex Subtelomeric Duplications during the Ev...A Cascade of Complex Subtelomeric Duplications during the Evolution of the Hominoid and Old World Monkey Genomes
The American Journal of Human Genetics, Volume 70, Issue 1, 1 January 2002, Pages 269-278
Michel van Geel, Evan E. Eichler, Amy F. Beck, Zhihong Shan, Thomas Haaf, Silvère M. van der Maarel, Rune R. Frants and Pieter J. de Jong
AbstractSubtelomeric duplications of an obscure tubulin “genic” segment located near the telomere of human chromosome 4q35 have occurred at different evolutionary time points within the last 25 million years of the catarrhine (i.e., hominoid and Old World monkey) evolution. The analyses of these segments reported here indicate an exceptional level of evolutionary instability. Substantial intra- and interspecific differences in copy number and distribution are observed among cercopithecoid (Old World monkey) and hominoid genomes. Characterization of the hominoid duplicated segments reveals a strong positional bias within pericentromeric and subtelomeric regions of the genome. On the basis of phylogenetic analysis from predicted proteins and comparisons of nucleotide-substitution rates, we present evidence of a conserved b-tubulin gene among the duplications. Remarkably, the evolutionary conservation has occurred in a nonorthologous fashion, such that the functional copy has shifted its positional context between hominoids and cercopithecoids. We propose that, in a chimpanzee-human common ancestor, one of the paralogous copies assumed the original function, whereas the ancestral copy acquired mutations and eventually became silenced. Our analysis emphasizes the dynamic nature of duplication-mediated genome evolution and the delicate balance between gene acquisition and silencing.
Abstract | | - …more
