Nachman M W, Boyer S N, Aquadro C F
Section of Genetics and Development, Cornell University, Ithaca, NY 14853-2703.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6364-8. doi: 10.1073/pnas.91.14.6364.
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.
分子进化的中性理论认为，虽然许多突变是有害的，并会迅速从种群中消除，但我们在种群中观察到的多态性突变在功能上彼此等效，因此在适应性方面是中性的。线粒体DNA（mtDNA）在进化研究中被广泛用作遗传标记，通常假定其根据严格的分子进化中性模型进化。中性理论的一个预测是，物种内部和物种之间的替换（非同义）与沉默（同义）核苷酸替换的比率将是相同的。我们通过测量56只家鼠（小家鼠）线粒体编码的NADH脱氢酶亚基3（ND3）基因的DNA序列变异来检验这一预测。我们还将小家鼠的ND3序列与小鼠和西班牙小鼠的ND3序列进行了比较。与小鼠或西班牙小鼠相比，小家鼠内部观察到的替换多态性数量明显多于预期。这一结果挑战了mtDNA根据严格中性模型进化的传统观点。然而，这一结果与分子进化的近中性模型一致，并表明该基因的大多数氨基酸多态性可能略有有害。
