Rice Daniel P, Good Benjamin H, Desai Michael M
Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138.
Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138 Department of Physics, Harvard University, Cambridge, Massachusetts 02138.
Genetics. 2015 May;200(1):321-9. doi: 10.1534/genetics.114.173815. Epub 2015 Mar 10.
The distribution of fitness effects (DFE) of new mutations is a key parameter in determining the course of evolution. This fact has motivated extensive efforts to measure the DFE or to predict it from first principles. However, just as the DFE determines the course of evolution, the evolutionary process itself constrains the DFE. Here, we analyze a simple model of genome evolution in a constant environment in which natural selection drives the population toward a dynamic steady state where beneficial and deleterious substitutions balance. The distribution of fitness effects at this steady state is stable under further evolution and provides a natural null expectation for the DFE in a population that has evolved in a constant environment for a long time. We calculate how the shape of the evolutionarily stable DFE depends on the underlying population genetic parameters. We show that, in the absence of epistasis, the ratio of beneficial to deleterious mutations of a given fitness effect obeys a simple relationship independent of population genetic details. Finally, we analyze how the stable DFE changes in the presence of a simple form of diminishing-returns epistasis.
新突变的适应性效应分布（DFE）是决定进化进程的关键参数。这一事实促使人们付出巨大努力来测量DFE或从基本原理预测它。然而，正如DFE决定进化进程一样，进化过程本身也会限制DFE。在这里，我们分析了一个在恒定环境中基因组进化的简单模型，在该模型中，自然选择驱使种群趋向于一个动态稳定状态，在这个状态下有益和有害的替换达到平衡。在这个稳定状态下的适应性效应分布在进一步进化过程中是稳定的，并且为在恒定环境中长时间进化的种群中的DFE提供了一个自然的零期望。我们计算了进化稳定的DFE的形状如何依赖于潜在的种群遗传参数。我们表明，在没有上位性的情况下，具有给定适应性效应的有益突变与有害突变的比例遵循一个独立于种群遗传细节的简单关系。最后，我们分析了在存在一种简单形式的收益递减上位性时稳定的DFE是如何变化的。
