Unexpectedly similar rates of nucleotide substitution found in male and female hominids
Unexpectedly similar rates of nucleotide substitution found in male and female hominids
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DOI：
10.1038/35020557
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发表时间：
2000-08-10
期刊：
影响因子：
64.8
通讯作者：
Page, DC
中科院分区：
文献类型：
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作者：
Bohossian, HB;Skaletsky, H;Page, DC
1947年，有人提出，在人类中，男性生殖系的突变率明显高于女性生殖系（1）。这一假设得到了以下观察结果的支持：在灵长类动物中，Y连锁基因比同源X连锁基因进化得更快（2-6）。基于这些进化研究，灵长类动物中雄性与雌性突变率的比值（α（m））估计约为5。然而，选择可能在内含子和外显子中具有偏斜的序列进化（7-10）。此外，研究的一些X-Y基因对位于具有显著不同核苷酸序列的染色体区域内（7，11，12）。在这里，我们直接比较人类X和Y序列在一个大区域内没有已知的基因。在这里，两条染色体有99%是相同的，而X-Y分歧仅在三、四百万年前的原始人类进化过程中才开始（13-15）。在猿类中，同源序列只存在于X染色体上。我们测序并比较了38.6 kb的这一区域从人类X，人类Y，黑猩猩X和大猩猩X染色体。我们计算出α（m）为1.7（95%置信区间为1.15-2.87），显著低于灵长类动物先前的估计值。我们推断，在人类和他们的直系祖先中，男性和女性的突变率远比以前想象的要相似。
In 1947, it was suggested that, in humans, the mutation rate is dramatically higher in the male germ line than in the female germ line(1). This hypothesis has been supported by the observation that, among primates, Y-linked genes evolved more rapidly than homologous X-linked genes(2-6). Based on these evolutionary studies, the ratio (alpha(m)) of male to female mutation rates in primates was estimated to be about 5. However, selection could have skewed sequence evolution in introns and exons(7-10). In addition, some of the X-Y gene pairs studied lie within chromosomal regions with substantially divergent nucleotide sequences(7,11,12). Here we directly compare human X and Y sequences within a large region with no known genes. Here the two chromosomes are 99% identical, and X-Y divergence began only three or four million years ago, during hominid evolution(13-15). In apes, homologous sequences exist only on the X chromosome. We sequenced and compared 38.6 kb of this region from human X, human Y, chimpanzee X and gorilla X chromosomes. We calculated alpha(m) to be 1.7 (95% confidence interval 1.15-2.87), significantly lower than previous estimates in primates. We infer that, in humans and their immediate ancestors, male and female mutation rates were far more similar than previously supposed.