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Science 9 January 2004:
Vol. 303. no. 5655, pp. 223 - 226
DOI: 10.1126/science.1088434
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Reports

Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA

Eduardo Ruiz-Pesini,1 Dan Mishmar,1 Martin Brandon,1,2 Vincent Procaccio,1 Douglas C. Wallace1*

A phylogenetic analysis of 1125 global human mitochondrial DNA (mtDNA) sequences permitted positioning of all nucleotide substitutions according to their order of occurrence. The relative frequency and amino acid conservation of internal branch replacement mutations was found to increase from tropical Africa to temperate Europe and arctic northeastern Siberia. Particularly highly conserved amino acid substitutions were found at the roots of multiple mtDNA lineages from higher latitudes. These same lineages correlate with increased propensity for energy deficiency diseases as well as longevity. Thus, specific mtDNA replacement mutations permitted our ancestors to adapt to more northern climates, and these same variants are influencing our health today.

1 Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, CA 92697-3940, USA.
2 Information & Computer Science, Institute for Genomics & Bioinformatics, University of California, Irvine, CA 92697-3425, USA.

* To whom correspondence should be addressed. E-mail: dwallace{at}uci.edu

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