Nonneutral Mitochondrial DNA Variation in Humans and Chimpanzees

INVESTIGATIONS

Nonneutral Mitochondrial DNA Variation in Humans and Chimpanzees

M. W. Nachman, W. M. Brown, M. Stoneking and C. F. Aquadro
Section of Genetics and Development, Cornell University, Ithaca, New York 14853

We sequenced the NADH dehydrogenase subunit 3 (ND3) gene from a sample of 61 humans, five common chimpanzees, and one gorilla to test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution. Within humans and within chimpanzees, the ratio of replacement to silent nucleotide substitutions was higher than observed in comparisons between species, contrary to neutral expectations. To test the generality of this result, we reanalyzed published human RFLP data from the entire mitochondrial genome. Gains of restriction sites relative to a known human mtDNA sequence were used to infer unambiguous nucleotide substitutions. We also compared the complete mtDNA sequences of three humans. Both the RFLP data and the sequence data reveal a higher ratio of replacement to silent nucleotide substitutions within humans than is seen between species. This pattern is observed at most or all human mitochondrial genes and is inconsistent with a strictly neutral model. These data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases.

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				T. Kivisild, P. Shen, D. P. Wall, B. Do, R. Sung, K. Davis, G. Passarino, P. A. Underhill, C. Scharfe, A. Torroni, et al. The Role of Selection in the Evolution of Human Mitochondrial Genomes Genetics, January 1, 2006; 172(1): 373 - 387. [Abstract] [Full Text] [PDF]

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				B. C. Verrelli and W. F. Eanes Extensive Amino Acid Polymorphism at the Pgm Locus Is Consistent With Adaptive Protein Evolution in Drosophila melanogaster Genetics, December 1, 2000; 156(4): 1737 - 1752. [Abstract] [Full Text]

				D. M. Weinreich and D. M. Rand Contrasting Patterns of Nonneutral Evolution in Proteins Encoded in Nuclear and Mitochondrial Genomes Genetics, September 1, 2000; 156(1): 385 - 399. [Abstract] [Full Text]

				J. D. Wall and M. Przeworski When Did the Human Population Size Start Increasing? Genetics, August 1, 2000; 155(4): 1865 - 1874. [Abstract] [Full Text]

				R. Nielsen and D. M. Weinreich The Age of Nonsynonymous and Synonymous Mutations in Animal mtDNA and Implications for the Mildly Deleterious Theory Genetics, September 1, 1999; 153(1): 497 - 506. [Abstract] [Full Text]

				H. Akashi Inferring the Fitness Effects of DNA Mutations From Polymorphism and Divergence Data: Statistical Power to Detect Directional Selection Under Stationarity and Free Recombination Genetics, January 1, 1999; 151(1): 221 - 238. [Abstract] [Full Text]

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				C. T. Bergstrom and J. Pritchard Germline Bottlenecks and the Evolutionary Maintenance of Mitochondrial Genomes Genetics, August 1, 1998; 149(4): 2135 - 2146. [Abstract] [Full Text] [PDF]

				J. Garcia-Martinez, J. A. Castro, M. Ramon, A. Latorre, and A. Moya Mitochondrial DNA Haplotype Frequencies in Natural and Experimental Populations of Drosophila subobscura Genetics, July 1, 1998; 149(3): 1377 - 1382. [Abstract] [Full Text] [PDF]

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