Hermisson Joachim, Hansen Thomas F, Wagner Günter P
Department of Ecology and Evolutionary Biology, Yale University, P.O. Box 208106, New Haven, Connecticut 06520-8106, USA.
Am Nat. 2003 May;161(5):708-34. doi: 10.1086/374204. Epub 2003 May 2.
We consider the effects of epistasis in a polygenic trait in the balance of mutation and stabilizing selection. The main issues are the genetic variation maintained in equilibrium and the evolution of the mutational effect distribution. The model assumes symmetric mutation and a continuum of alleles at all loci. Epistasis is modeled proportional to pairwise products of the single-locus effects. A general analytical formalism is developed. Assuming linkage equilibrium, we derive results for the equilibrium mutation load and the genetic and mutational variance in the house of cards and the Gaussian approximation. The additive genetic variation maintained in mutation-selection balance is reduced by any pattern of the epistatic interactions. The mutational variance, in contrast, is often increased. Large differences in mutational effects among loci emerge, and a negative correlation among (standard mean) locus mutation effects and mutation rates is predicted. Contrary to the common view since Waddington, we find that stabilizing selection in general does not lead to canalization of the trait. We propose that canalization as a target of selection instead occurs at the genic level. Here, primarily genes with a high mutation rate are buffered, often at the cost of decanalization of other genes. An intuitive interpretation of this view is given in the discussion.
我们在突变与稳定选择的平衡中考虑上位性对多基因性状的影响。主要问题是平衡状态下维持的遗传变异以及突变效应分布的演变。该模型假设所有位点存在对称突变和一系列等位基因。上位性建模为与单一位点效应的成对乘积成比例。我们开发了一种通用的分析形式体系。假设连锁平衡，我们推导了在“纸牌屋”模型和高斯近似下平衡突变负荷、遗传方差和突变方差的结果。上位性相互作用的任何模式都会降低突变 - 选择平衡中维持的加性遗传变异。相反，突变方差通常会增加。位点间的突变效应出现很大差异，并且预测（标准均值）位点突变效应与突变率之间存在负相关。与自沃丁顿以来的普遍观点相反，我们发现稳定选择通常不会导致性状的发育稳态。我们提出，作为选择目标的发育稳态反而发生在基因水平。在这里，主要是高突变率的基因受到缓冲，这通常以其他基因的发育稳态丧失为代价。在讨论中给出了对此观点的直观解释。
