Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18034-9. doi: 10.1073/pnas.1004666107. Epub 2010 Sep 27.
Pleiotropy refers to the phenomenon of a single mutation or gene affecting multiple distinct phenotypic traits and has broad implications in many areas of biology. Due to its central importance, pleiotropy has also been extensively modeled, albeit with virtually no empirical basis. Analyzing phenotypes of large numbers of yeast, nematode, and mouse mutants, we here describe the genomic patterns of pleiotropy. We show that the fraction of traits altered appreciably by the deletion of a gene is minute for most genes and the gene-trait relationship is highly modular. The standardized size of the phenotypic effect of a gene on a trait is approximately normally distributed with variable SDs for different genes, which gives rise to the surprising observation of a larger per-trait effect for genes affecting more traits. This scaling property counteracts the pleiotropy-associated reduction in adaptation rate (i.e., the "cost of complexity") in a nonlinear fashion, resulting in the highest adaptation rate for organisms of intermediate complexity rather than low complexity. Intriguingly, the observed scaling exponent falls in a narrow range that maximizes the optimal complexity. Together, the genome-wide observations of overall low pleiotropy, high modularity, and larger per-trait effects from genes of higher pleiotropy necessitate major revisions of theoretical models of pleiotropy and suggest that pleiotropy has not only allowed but also promoted the evolution of complexity.
多效性是指单个突变或基因影响多个不同表型特征的现象，在生物学的许多领域都具有广泛的意义。由于其核心重要性，多效性也被广泛建模，尽管几乎没有实证依据。通过分析大量酵母、线虫和小鼠突变体的表型，我们在这里描述了多效性的基因组模式。我们表明，对于大多数基因来说，由于单个基因缺失而显著改变的特征比例非常小，而且基因-特征关系具有高度的模块性。基因对特征的表型效应的标准化大小大致呈正态分布，不同基因的标准差不同，这导致了一个令人惊讶的观察结果，即影响更多特征的基因的每个特征的效应更大。这种缩放特性以非线性的方式抵消了与多效性相关的适应率降低（即“复杂性成本”），从而导致中等复杂性而不是低复杂性的生物体具有最高的适应率。有趣的是，观察到的缩放指数落在一个狭窄的范围内，最大限度地提高了最佳复杂性。总之，对整体低多效性、高模块性和来自高多效性基因的更大特征效应的全基因组观察结果，需要对多效性的理论模型进行重大修订，并表明多效性不仅允许而且促进了复杂性的进化。
