Open AccessThe Age of Nonsynonymous and Synonymous Mutations in Animal mtDNA and Implications for the Mildly Deleterious Theory
Author(s) -
Rasmus Nielsen,
Daniel Weinreich
Publication year - 1999
Publication title -
genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.792
H-Index - 246
eISSN - 1943-2631
pISSN - 0016-6731
DOI - 10.1093/genetics/153.1.497
Subject(s) - nonsynonymous substitution , biology , genetics , mitochondrial dna , mutation , neutral theory of molecular evolution , negative selection , selection (genetic algorithm) , synonymous substitution , evolutionary biology , gene , genome , codon usage bias , artificial intelligence , computer science
McDonald/Kreitman tests performed on animal mtDNA consistently reveal significant deviations from strict neutrality in the direction of an excess number of polymorphic nonsynonymous sites, which is consistent with purifying selection acting on nonsynonymous sites. We show that under models of recurrent neutral and deleterious mutations, the mean age of segregating neutral mutations is greater than the mean age of segregating selected mutations, even in the absence of recombination. We develop a test of the hypothesis that the mean age of segregating synonymous mutations equals the mean age of segregating nonsynonymous mutations in a sample of DNA sequences. The power of this age-of-mutation test and the power of the McDonald/Kreitman test are explored by computer simulations. We apply the new test to 25 previously published mitochondrial data sets and find weak evidence for selection against nonsynonymous mutations.