Lynch Michael, Blanchard Jeff, Houle David, Kibota Travis, Schultz Stewart, Vassilieva Larissa, Willis John
Department of Biology, University of Oregon, Eugene, Oregon, 97403.
Department of Zoology, University of Toronto, Toronto, Ontario, M5S 1A1, Canada.
Evolution. 1999 Jun;53(3):645-663. doi: 10.1111/j.1558-5646.1999.tb05361.x.
Mildly deleterious mutation has been invoked as a leading explanation for a diverse array of observations in evolutionary genetics and molecular evolution and is thought to be a significant risk of extinction for small populations. However, much of the empirical evidence for the deleterious-mutation process derives from studies of Drosophila melanogaster, some of which have been called into question. We review a broad array of data that collectively support the hypothesis that deleterious mutations arise in flies at rate of about one per individual per generation, with the average mutation decreasing fitness by about only 2% in the heterozygous state. Empirical evidence from microbes, plants, and several other animal species provide further support for the idea that most mutations have only mildly deleterious effects on fitness, and several other species appear to have genomic mutation rates that are of the order of magnitude observed in Drosophila. However, there is mounting evidence that some organisms have genomic deleterious mutation rates that are substantially lower than one per individual per generation. These lower rates may be at least partially reconciled with the Drosophila data by taking into consideration the number of germline cell divisions per generation. To fully resolve the existing controversy over the properties of spontaneous mutations, a number of issues need to be clarified. These include the form of the distribution of mutational effects and the extent to which this is modified by the environmental and genetic background and the contribution of basic biological features such as generation length and genome size to interspecific differences in the genomic mutation rate. Once such information is available, it should be possible to make a refined statement about the long-term impact of mutation on the genetic integrity of human populations subject to relaxed selection resulting from modern medical procedures.
轻度有害突变已被视为进化遗传学和分子进化中一系列观察结果的主要解释，并且被认为是小种群灭绝的重大风险。然而，有害突变过程的许多实证证据来自对黑腹果蝇的研究，其中一些研究受到了质疑。我们回顾了大量数据，这些数据共同支持了这样一种假设，即果蝇中有害突变的产生速率约为每代每个个体一个，杂合状态下的平均突变使适应性降低约2%。来自微生物、植物和其他几种动物物种的实证证据进一步支持了这样一种观点，即大多数突变对适应性只有轻微的有害影响，并且其他一些物种的基因组突变率似乎与在果蝇中观察到的数量级相同。然而，越来越多的证据表明，一些生物体的基因组有害突变率远低于每代每个个体一个。通过考虑每代生殖细胞分裂的数量，这些较低的速率可能至少部分与果蝇的数据相协调。为了完全解决关于自发突变特性的现有争议，需要澄清一些问题。这些问题包括突变效应分布的形式、环境和遗传背景对其的修饰程度，以及诸如世代长度和基因组大小等基本生物学特征对基因组突变率种间差异的贡献。一旦获得此类信息，就应该能够对现代医疗程序导致选择放松的情况下，突变对人类种群遗传完整性的长期影响做出更精确的说明。
