Cherry J L
Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112-5330, USA.
Genetics. 1998 Oct;150(2):911-9. doi: 10.1093/genetics/150.2.911.
The rate of nucleotide substitution is generally believed to be a decreasing function of effective population size, at least for nonsynonymous substitutions. This view was originally based on consideration of slightly deleterious mutations with a fixed distribution of selection coefficients. A realistic model must include the occurrence and fixation of some advantageous mutations that compensate for the loss of fitness due to deleterious substitutions. Some such models, such as so-called "fixed" models, also predict a population size effect on substitution rate. An alternative model, presented here, predicts the near absence of a population size effect on substitution rate. This model is based on concave log-fitness functions and a fixed distribution of mutational effects on the selectively important trait. Simulations of an instance of the model confirm the approximate insensitivity of the substitution rate to population size. Although much experimental evidence has been claimed to support the existence of a population size effect, the body of evidence as a whole is equivocal, and much of the evidence that is supposed to demonstrate such an effect would also suggest that it is very small. Perhaps the proposed model applies well to some genes and not so well to others, and genes therefore vary with regard to the population size effect.
一般认为，核苷酸替换率是有效种群大小的递减函数，至少对于非同义替换来说是这样。这一观点最初是基于对具有固定选择系数分布的轻微有害突变的考虑。一个现实的模型必须包括一些有利突变的发生和固定，这些有利突变可以补偿有害替换导致的适应性损失。一些这样的模型，比如所谓的“固定”模型，也预测种群大小对替换率有影响。这里提出的一个替代模型预测，种群大小对替换率几乎没有影响。这个模型基于凹形对数适应度函数以及对选择性重要性状的突变效应的固定分布。对该模型一个实例的模拟证实了替换率对种群大小的近似不敏感性。尽管有许多实验证据声称支持种群大小效应的存在，但总体证据是模棱两可的，而且许多本应证明这种效应的证据也表明它非常小。也许所提出的模型对某些基因适用得很好，而对其他基因则不太适用，因此基因在种群大小效应方面存在差异。
