Natural selection shaped regional mtDNA variation in human

Cornell University, Итак, New York, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2003; 100(1):171-6. DOI: 10.1073/pnas.0136972100
Source: PubMed


Human mtDNA shows striking regional variation, traditionally attributed to genetic drift. However, it is not easy to account for the fact that only two mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C, D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative to drift, natural selection might have enriched for certain mtDNA lineages as people migrated north into colder climates. To test this hypothesis we analyzed 104 complete mtDNA sequences from all global regions and lineages. African mtDNA variation did not significantly deviate from the standard neutral model, but European, Asian, and Siberian plus Native American variations did. Analysis of amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations (synonymous, Ks) (kaks) for all 13 mtDNA protein-coding genes revealed that the ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene, even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the kaks ratios for each mtDNA gene from the tropical, temperate, and arctic zones revealed that ATP6 was highly variable in the mtDNAs from the arctic zone, cytochrome b was particularly variable in the temperate zone, and cytochrome oxidase I was notably more variable in the tropics. Moreover, multiple amino acid changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be functionally significant. From these analyses we conclude that selection may have played a role in shaping human regional mtDNA variation and that one of the selective influences was climate.

Download full-text


Available from: Dan Mishmar
    • "It has been surmised that climatic pressures led to positive evolutionary selection for specific mitochondrial gene polymorphisms that lower oxidative phosphorylation (OXPHOS) coupling efficiency in favor of greater heat production, conferring survival advantage for populations habituating cold climates (Mishmar et al., 2003; Ruiz-Pesini et al., 2004). Previous studies have examined the selection hypothesis using the dN/dS (K a /K s ) ratio (Mishmar et al., 2003). This ratio defines the number of non-synonymous substitutions per non-synonymous site (K a ) to the number of synonymous substitutions per synonymous site (K s ). "
    [Show abstract] [Hide abstract]
    ABSTRACT: During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation.
    No preview · Article · Dec 2015 · Scandinavian Journal of Medicine and Science in Sports
  • Source
    • "mtDNA in some mammal and fish species (Finch et al., 2014; Foote et al., 2011; Garvin et al., 2011; Hassanin et al., 2009; Menezes et al., 2013; Shen et al., 2010). However, the majority of mtDNA mutations observed within a species appear to be more subtle, slightly deleterious mutations that rarely become fixed within a species, making their effects on phenotypes harder to dissect (Mishmar et al., 2003). While mtDNA mutations linked to impairment or enhancement of metabolic processes are increasingly well recognized (Taylor & Turnbull, 2005; Wallace, 2005), new research is identifying numerous other ways in which mtDNA mutations may affect phenotypes, including those associated with disease. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The mitochondrial genome (mtDNA) is distinct from the nuclear genome and is known to play a significant role in several disease phenotypes, such as longevity and fertility. Here we characterize the complete mitochondrial genomes (∼16 590 bp), and the extent of within and between strain variation for 27 adult zebrafish, representing five commonly used laboratory strains (AB, TL, HL, WIK, and SJD) and one line acquired from a local pet shop. These data were subsequently analyzed to determine the phylogenetic relationships between strains and ascertain if positive selection might be operating on any mtDNA genes. Relationships between strains are not entirely consistent with those observed previously using nuclear DNA. Further there is a substantial body of variation within current zebrafish lines, with 172 variants described across lines. Of these, 27 changes are non-synonymous and there is nominal evidence for positive selection in the mtDNA sequences at some of these sites. We further identify novel frameshift mutations in eight genes, which are all predicted to have functional consequences. Our study provides the first information on mtDNA diversity in zebrafish, identifies multiple non-synonymous substitutions and other mutations expected to have functional effects, and represents an important first step in establishing zebrafish as a model for investigating the phenotypic effects of mtDNA mutations.
    Full-text · Article · Oct 2015 · Mitochondrial DNA
  • Source
    • "Table 1 Estimated ages (years) for different subclades of West Eurasian haplogroups in India a Mutation rate of Mishmar et al. (2003) "

    Full-text · Article · Apr 2015 · Human Genetics
Show more