title: Nonneutral mitochondrial DNA variation in humans and chimpanzees.
abstract: 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.
authors.affiliation: Section of Genetics and Development, Cornell University, Ithaca, New York 14853, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Nachman
authors.forename: W M
authors.initials: WM
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Stoneking
authors.forename: C F
authors.initials: CF
authors.lastname: Aquadro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004272:DNA, Mitochondrial; D014644:Genetic Variation; D015894:Genome, Human; D006071:Gorilla gorilla / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004272:DNA, Mitochondrial; D009245:NADH Dehydrogenase