The Pleiotropy Hypothesis of Molecular Evolution

AbstractUnder the nearly-neutral model of protein evolution, the evolutionary rate is virtually determined by the selection intensity (S), which can be decomposed into S=-KxB0, where K is the gene pleiotropy defined by the number of fitness-related traits (molecular phenotypes) and B0 is the baseline of the selection intensity. Hence, the variation of S (sequence conservation) among genes may have two resources: one is the variation of gene pleiotropy among genes (K-mode), and the other is the variation of baseline intensity among genes (B-mode). While K can be effectively estimated (denoted by Ke) based on the phylogenetic analysis of protein sequences, the correlation between Ke and empirical pleiotropy measures remains uninvestigated. In this paper, we show positive correlations of effective gene pleiotropy with protein-protein interactions, expression broadness, enzyme connections, and involved biological processes. We thus propose the pleiotropy hypothesis (K-mode), suggesting that the rate variation among proteins is mainly due to the variation of gene pleiotropy, revealing a sophisticated display of multiple gene functionality.