期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：6
页码：1662-1669
DOI：10.1073/pnas.1423275112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe extent and causes of genetic variation have been debated for 60 y. This paper synthesizes evidence from studies of DNA sequence variability in Drosophila and from experiments on the quantitative genetics of fitness components. Two major conclusions emerge. First, a class of mutations with relatively large fitness effects contributes importantly to both the overall effect of new mutations on fitness components and to standing variation. These mutations are not detected in analyses of sequence variability. Second, a large fraction of variability in fitness components must be maintained by selection rather than reflecting deleterious variants introduced by mutation. These results imply that both approaches to the study of natural variation are needed to obtain a complete understanding of its causes. DNA sequencing has revealed high levels of variability within most species. Statistical methods based on population genetics theory have been applied to the resulting data and suggest that most mutations affecting functionally important sequences are deleterious but subject to very weak selection. Quantitative genetic studies have provided information on the extent of genetic variation within populations in traits related to fitness and the rate at which variability in these traits arises by mutation. This paper attempts to combine the available information from applications of the two approaches to populations of the fruitfly Drosophila in order to estimate some important parameters of genetic variation, using a simple population genetics model of mutational effects on fitness components. Analyses based on this model suggest the existence of a class of mutations with much larger fitness effects than those inferred from sequence variability and that contribute most of the standing variation in fitness within a population caused by the input of mildly deleterious mutations. However, deleterious mutations explain only part of this standing variation, and other processes such as balancing selection appear to make a large contribution to genetic variation in fitness components in Drosophila.
