David M. Rand and Lisa M. Kann
Department of Ecology and Evolutionary Biology
Brown University
Providence, RI  02912
 
 

Running Head:  Excess amino acid polymorphism in mtDNA

Keywords: mitochondrial DNA, neutral theory, natural selection, mildly deleterious mutations, genetic variation, Drosophila, human
 

Address for correspondence:  David M. Rand, Department of Ecology and Evolutionary Biology, Brown University, Box G, Providence, RI  02912  Phone: (401) 863-2890, Fax: (401) 863-2166, email: David_Rand@brown.edu

 Abstract
 Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species.  To examine further this pattern of non-neutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans .  Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations.  The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test.  These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6).  Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism.  Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954).  These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species, but do not contribute to divergence.  The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations.  Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal.  While the mildly deleterious model fits as a net effect in the evolution of non-recombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.