Nonneutral evolution at the mitochondrial NADH dehydrogenase subunit 3 gene in mice.
The neutral theory of molecular evolution asserts that while many mutations are deleterious and rapidly eliminated from populations, those that we observe as polymorphisms within populations are functionally equivalent to each other and thus neutral with respect to fitness. Mitochondrial DNA (mtDNA) is widely used as a genetic marker in evolutionary studies and is generally assumed to evolve according to a strictly neutral model of molecular evolution. One prediction of the neutral theory is that the ratio of replacement (nonsynonymous) to silent (synonymous) nucleotide substitutions will be the same within and between species. We tested this prediction by measuring DNA sequence variation at the mitochondrially encoded NADH dehydrogenase subunit 3 (ND3) gene among 56 individual house mice, Mus domesticus. We also compared ND3 sequence from M. domesticus to ND3 sequence from Mus musculus and Mus spretus. A significantly greater number of replacement polymorphisms were observed within M. domesticus than expected based on comparisons to either M. musculus or M. spretus. This result challenges the conventional view that mtDNA evolves according to a strictly neutral model. However, this result is consistent with a nearly neutral model of molecular evolution and suggests that most amino acid polymorphisms at this gene may be slightly deleterious.
Section of Genetics and Development, Cornell University, Ithaca, NY 14853-2703.
M W
MW
Nachman
S N
SN
Boyer
C F
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Aquadro
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017124:Conserved Sequence; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D046911:Macromolecular Substances; D051379:Mice / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics*; D009245:NADH Dehydrogenase / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D004272:DNA, Mitochondrial; D046911:Macromolecular Substances; D009245:NADH Dehydrogenase