Crow J F
Genetics Laboratory, University of Wisconsin, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8380-6. doi: 10.1073/pnas.94.16.8380.
The human mutation rate for base substitutions is much higher in males than in females and increases with paternal age. This effect is mainly, if not entirely, due to the large number of cell divisions in the male germ line. The mutation-rate increase is considerably greater than expected if the mutation rate were simply proportional to the number of cell divisions. In contrast, those mutations that are small deletions or rearrangements do not show the paternal age effect. The observed increase with the age of the father in the incidence of children with different dominant mutations is variable, presumably the result of different mixtures of base substitutions and deletions. In Drosophila, the rate of mutations causing minor deleterious effects is estimated to be about one new mutation per zygote. Because of a larger number of genes and a much larger amount of DNA, the human rate is presumably higher. Recently, the Drosophila data have been reanalyzed and the mutation-rate estimate questioned, but I believe that the totality of evidence supports the original conclusion. The most reasonable way in which a species can cope with a high mutation rate is by quasi-truncation selection, whereby a number of mutant genes are eliminated by one "genetic death."
人类碱基替换的突变率在男性中比女性高得多，并且随着父亲年龄的增长而增加。这种效应主要（如果不是完全）归因于雄性生殖系中大量的细胞分裂。如果突变率仅仅与细胞分裂的数量成正比，那么突变率的增加会比预期大得多。相比之下，那些小缺失或重排的突变则没有显示出父亲年龄效应。观察到不同显性突变患儿的发病率随父亲年龄增加而有所不同，这可能是碱基替换和缺失不同组合的结果。在果蝇中，导致轻微有害效应的突变率估计约为每个受精卵一个新突变。由于基因数量更多和DNA数量多得多，人类的突变率可能更高。最近，果蝇的数据被重新分析，突变率估计受到质疑，但我认为所有证据都支持最初的结论。一个物种应对高突变率的最合理方式是通过准截断选择，即通过一次“基因死亡”消除一些突变基因。
