Pleiotropic Effects of Beneficial Mutations in Escherichia Coli

Abstract

Micromutational models of adaptation have placed considerable weight on antagonistic pleiotropy as a mechanism that prevents mutations of large effect from achieving fixation. However, there are few empirical studies of the distribution of pleiotropic effects, and no studies that have examined this distribution for a large number of adaptive mutations. Here we examine the form and extent of pleiotropy associated with beneficial mutations in Escherichia coli. To do so, we used a collection of independently evolved genotypes, each of which contains a beneficial mutation that confers increased fitness in a glucose-limited environment. To determine the pleiotropic effects of these mutations, we examined the fitnesses of the mutants in five novel resource environments. Our results show that the majority of mutations had significant fitness effects in alternative resources, such that pleiotropy was common. The predominant form of this pleiotropy was positive--that is, most mutations that conferred increased fitness in glucose also conferred increased fitness in novel resources. We did detect some deleterious pleiotropic effects, but they were primarily limited to one of the five resources, and within this resource, to only a subset of mutants. Although pleiotropic effects were generally positive, fitness levels were lower and more variable on resources that differed most in their mechanisms of uptake and catabolism from that of glucose. Positive pleiotropic effects were strongly correlated in magnitude with their direct effects, but no such correlation was found among mutants with deleterious pleiotropic effects. Whereas previous studies of populations evolved on glucose for longer periods of time showed consistent declines on some of the resources used here, our results suggest that deleterious pleiotropic effects were limited to only a subset of the beneficial mutations available.

The Environment Affects Epistatic Interactions to Alter the Topology of an Empirical Fitness Landscape

“…In an effort to distinguish these explanations, one study specifically focused on pleiotropic effects of beneficial mutations in five different environments. Mutations that were beneficial in the selected environment tended to be beneficial in others, and although there were exceptions, limited antagonistic pleiotropy was observed [45], [46]. Here, we also report limited antagonistic pleiotropy with five beneficial mutations with an increased sample size of 1,920 environments from our initial Biolog screen (Table S1).…”

Evolution of Escherichia coli rifampicin resistance in an antibiotic-free environment during thermal stress

“…With the exception of lethal selection or niche creation [11] experiments, most other studies have demonstrated that the fitness advantage conferred by a mutation is maintained across environments and conditions [9,10]. In other words, they have found that beneficial mutations are generally not severely compromised in other environments [10].…”

The Genomic Landscape and Evolutionary Resolution of Antagonistic Pleiotropy in Yeast

“…Early artificial selection experiments showed that improving one trait often worsens another, suggesting that AP is not uncommon (Mather and Harrison, 1949; Rice, 1992; Cooper and Lenski, 2000; Ostrowski et al, 2005). Consistently, a Drosophila study proposed over 1000 candidate genes that are subject to sexual antagonism, based on correlations between gene expression levels and organismal fitness across 15 genotypes and two sexes (Innocenti and Morrow, 2010).…”