Nachman M W, Brown W M, Stoneking M, Aquadro C F
Section of Genetics and Development, Cornell University, Ithaca, New York 14853, USA.
Genetics. 1996 Mar;142(3):953-63. doi: 10.1093/genetics/142.3.953.
We sequenced the NADH dehydrogenase subunit 3 (ND3) gene from a sample of 61 humans, five common chimpanzees, and one gorilla to test whether patterns of mitochondrial DNA (mtDNA) variation are consistent with a neutral model of molecular evolution. Within humans and within chimpanzees, the ratio of replacement to silent nucleotide substitutions was higher than observed in comparisons between species, contrary to neutral expectations. To test the generality of this result, we reanalyzed published human RFLP data from the entire mitochondrial genome. Gains of restriction sites relative to a known human mtDNA sequence were used to infer unambiguous nucleotide substitutions. We also compared the complete mtDNA sequences of three humans. Both the RFLP data and the sequence data reveal a higher ratio of replacement to silent nucleotide substitutions within humans than is seen between species. This pattern is observed at most or all human mitochondrial genes and is inconsistent with a strictly neutral model. These data suggest that many mitochondrial protein polymorphisms are slightly deleterious, consistent with studies of human mitochondrial diseases.
我们对61名人类、5只普通黑猩猩和1只大猩猩的样本中的烟酰胺腺嘌呤二核苷酸脱氢酶亚基3（ND3）基因进行了测序，以检验线粒体DNA（mtDNA）变异模式是否与分子进化的中性模型一致。在人类和黑猩猩内部，替换型与沉默型核苷酸替换的比率高于物种间比较时观察到的比率，这与中性预期相反。为了检验这一结果的普遍性，我们重新分析了已发表的来自整个人类线粒体基因组的限制性片段长度多态性（RFLP）数据。相对于已知人类mtDNA序列的限制性酶切位点增加被用于推断明确的核苷酸替换。我们还比较了三个人类的完整mtDNA序列。RFLP数据和序列数据均显示，人类内部替换型与沉默型核苷酸替换的比率高于物种间的比率。这种模式在大多数或所有人类线粒体基因中都能观察到，并且与严格的中性模型不一致。这些数据表明，许多线粒体蛋白质多态性具有轻微的有害性，这与人类线粒体疾病的研究结果一致。
