Genomic patterns of pleiotropy and the evolution of complexity

摘要

Pleiotropy refers to the phenomenon of a single mutation or gene affecting multiple distinct phenotypic traits and has broad impli-cations 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 geno-mic 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 stan-dardized size of the phenotypic effect of a gene on a trait is ap-proximately 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 prop-erty 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 com-plexity rather than low complexity. Intriguingly, the observed scal-ing 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 theoret-ical models of pleiotropy and suggest that pleiotropy has not only allowed but also promoted the evolution of complexity.