摘要
The determinative view of mutation penetrance is a fundamental assumption for the building of molecular evolutionary theory:individuals in the population with the same genotype have the same fitness effect.Since this view has been constantly challenged by experimental evidence,it is desirable to examine to what extent violation of this view could affect our under-standing of molecular evolution.To this end,the author formulated a new theory of molecular evolution under a random model of penetrance:for any individual with the same mutational genotype,the coefficient of selection is a random variable.It follows that,in addition to the conventional Ne-genetic drift(Ne is the effective population size),the variance of penetrance among individuals(ε^(2))represents a new type of genetic drift,coined by theε^(2)-genetic drift.It has been demonstrated that these two genetic drifts together provided new insights on the nearly neutral evolution:the evolutionary rate is inversely related to the log-of-Ne when theε^(2)-genetic drift is nontrivial.This log-of-Ne feature ofε^(2)-genetic drift did explain well why the dN/dS ratio(the nonsynonymous rate to the synonymous rate)in humans is only as twofold as that in mice,while the effective population size(Ne)of mice is about two-magnitude larger than that of humans.It was estimated that,for the first time,the variance of random penetrance in mammalian genes was approximatelyε^(2)≈5.89×10^(-3).
基金
supported by the fund from Iowa State University.
