Gene Functional Trade-Offs and the Evolution of Pleiotropy

Abstract

Pleiotropy is the property of genes affecting multiple functions or characters of an organism. Genes vary widely in their degree of pleiotropy, but this variation is often considered a by-product of their evolutionary history. We present a functional theory of how pleiotropy may itself evolve. We consider genes that contribute to two functions, where contributing more to one function detracts from allocation to the second function. We show that whether genes become pleiotropic or specialize on a single function depends on the nature of trade-offs as gene activities contribute to different traits and on how the functionality of these traits affects fitness. In general, when a gene product can perform well at two functions, it evolves to do so, but not when pleiotropy would greatly disrupt each function. Consequently, reduced pleiotropy should often evolve, with genes specializing on the trait that is currently more important to fitness. Even when pleiotropy does evolve, not all genes are expected to become equally pleiotropic; genes with higher levels of expression are more likely to evolve greater pleiotropy. For the case of gene duplicates, we find that perfect subfunctionalization evolves only under stringent conditions. More often, duplicates are expected to maintain a certain degree of functional redundancy, with the gene contributing more to trait functionality evolving the highest degree of pleiotropy. Gene product interactions can facilitate subfunctionalization, but whether they do so depends on the curvature of the fitness surface. Finally, we find that stochastic gene expression favors pleiotropy by selecting for robustness in fitness components. PLEIOTROPY is the property whereby a gene affects more than one function or phenotypic character of an organism. Gene-knockout studies in yeast indicate that deleting genes with higher degrees of pleiotropy has, on average, a more harmful effect on fitness (Salathé et al. 2006; Cooper et al. 2007). This negative relationship with fitness is expected given that most mutational changes are deleterious so that the more characters are affected by a mutation, the more likely the net effect on fitness is harmful, even if the mutation is beneficial for a subset of characters. This claim has been verified in theoretical studies based on Fisher's geometrical model (Chevin et al. 2010;Lourenço et al. 2011). Pleiotropy is consequently seen as a constraint on evolution because it reduces the adaptive capacity of an organism (Orr 2000;Welch and Waxman 2003).Recent observations in a variety of species have found that the extent of pleiotropy varies among genes and is often limited, with a majority of genes influencing a small set of traits while a few genes affect many traits (Dudley et al. 2005; Albert et al. 2008;Wagner et al. 2008;Wang et al. 2010;Wagner and Zhang 2011). This is in direct opposition to the historical assumption of universal pleiotropy underlying most population and quantitative genetics approaches to the joint evolution of multiple characters (...

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