Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans

Recent studies of mitochondrial DNA (mtDNA) variation in mammals andDrosophila have shown an excess of amino acid variation within species(replacement polymorphism) relative to the number of silent and replacementdifferences fixed between species. To examine further this pattern ofnonneutral mtDNA evolution, we present sequence data for the ND3 and ND5genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans.Of interest are the frequency spectra of silent and replacementpolymorphisms, and potential variation among genes and taxa in thedepartures from neutral expectations. The Drosophila ND3 and ND5 data showno significant excess of replacement polymorphism using theMcDonald-Kreitman test. These data are in contrast to significantdepartures from neutrality for the ND3 gene in mammals and other genes inDrosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however,both Drosophila and human mtDNA show very significant excesses of aminoacid polymorphism. Silent polymorphisms at ND5 show a significantly highervariance in frequency than replacement polymorphisms, and the latter show asignificant skew toward low frequencies (Tajima's D = -1.954). Thesepatterns are interpreted in light of the nearly neutral theory where mildlydeleterious amino acid haplotypes are observed as ephemeral variants withinspecies but do not contribute to divergence. The patterns of polymorphismand divergence at charge-altering amino acid sites are presented for theDrosophila ND5 gene to examine the evolution of functionally distinctmutations. Excess charge-altering polymorphism is observed at the carboxylterminal and excess charge-altering divergence is detected at the aminoterminal. While the mildly deleterious model fits as a net effect in theevolution of nonrecombining mitochondrial genomes, these data suggest thatopposing evolutionary pressures may act on different regions ofmitochondrial genes and genomes.