Takahata N
National Institute of Genetics, Mishima, Japan.
Theor Popul Biol. 1991 Jun;39(3):329-44. doi: 10.1016/0040-5809(91)90027-d.
The most commonly used statistical model to describe the rate constancy of molecular evolution (molecular clock) is a simple Poisson process in which the variance of the number of amino acid or nucleotide substitutions in a particular gene should be equal to the mean and henceforth the dispersion index, the ratio of the variance to the mean, should be equal to one. Recent sequence data, however, have shown that the substitutional process in molecular evolution is often considerably overdispersed and have called into question the generality of using a simple Poisson process. Several efforts have been made to develop more realistic models of molecular evolution. In this paper, I will show that the spatial (site-specific) variation in the rate of molecular evolution is an improbable cause of the overdispersion and then review various statistical models which take the temporal variation into account. Although these models do not immediately specify what the mechanisms of molecular evolution might be, they do make qualitatively different predictions and give some insight into their inference. One way to distinguish them is suggested. In addition, effects of selected substitutions that presumably occur after a major change in a molecule are quasi-quantitatively examined. It is most likely that the overdispersion of molecular clock is due either to a major molecular reconfiguration (fluctuating neutral space) led by a series of subliminal neutral changes or to selected substitutions fine-tuning a molecule after a major molecular change. Although the latter possibility, of course, violates the simplest neutrality assumption, it would not impair the neutral theory as a whole.
描述分子进化速率恒定性（分子钟）最常用的统计模型是一个简单的泊松过程，其中特定基因中氨基酸或核苷酸替换数的方差应等于均值，因此分散指数（方差与均值之比）应等于1。然而，最近的序列数据表明，分子进化中的替换过程往往具有相当大的过度分散性，并对使用简单泊松过程的普遍性提出了质疑。人们已经做出了一些努力来开发更现实的分子进化模型。在本文中，我将表明分子进化速率的空间（位点特异性）变化不太可能是过度分散的原因，然后回顾各种考虑时间变化的统计模型。虽然这些模型没有立即说明分子进化的机制可能是什么，但它们确实做出了质的不同的预测，并对其推断提供了一些见解。提出了一种区分它们的方法。此外，还对推测在分子发生重大变化后发生的选择替换的影响进行了准定量研究。分子钟的过度分散很可能是由于一系列阈下中性变化导致的重大分子重新配置（波动的中性空间），或者是由于在分子发生重大变化后选择替换对分子进行微调。当然，后一种可能性违反了最简单的中性假设，但它不会损害整个中性理论。
