Fast Growth Increases the Selective Advantage of a Mutation Arising Recurrently during Evolution under Metal Limitation

Hsin-Hung Chou,Ivan Matic,Christopher J Marx,Julia Berthet

doi:10.1371/journal.pgen.1000652

Abstract

Understanding the evolution of biological systems requires untangling the molecular mechanisms that connect genetic and environmental variations to their physiological consequences. Metal limitation across many environments, ranging from pathogens in the human body to phytoplankton in the oceans, imposes strong selection for improved metal acquisition systems. In this study, we uncovered the genetic and physiological basis of adaptation to metal limitation using experimental populations of Methylobacterium extorquens AM1 evolved in metal-deficient growth media. We identified a transposition mutation arising recurrently in 30 of 32 independent populations that utilized methanol as a carbon source, but not in any of the 8 that utilized only succinate. These parallel insertion events increased expression of a novel transporter system that enhanced cobalt uptake. Such ability ensured the production of vitamin B12, a cobalt-containing cofactor, to sustain two vitamin B12–dependent enzymatic reactions essential to methanol, but not succinate, metabolism. Interestingly, this mutation provided higher selective advantages under genetic backgrounds or incubation temperatures that permit faster growth, indicating growth-rate–dependent epistatic and genotype-by-environment interactions. Our results link beneficial mutations emerging in a metal-limiting environment to their physiological basis in carbon metabolism, suggest that certain molecular features may promote the emergence of parallel mutations, and indicate that the selective advantages of some mutations depend generically upon changes in growth rate that can stem from either genetic or environmental influences.

Highlights

Adaptation is a product of genetic modification and natural selection imposed by environmental challenges
Despite having been discovered fortuitously, our work represents the first study to investigate the genetic basis of adaptation to metal limitation in an experimental evolution system
The highly parallel but distinct evolutionary consequences prompted us to investigate the physiological basis of adaptation and molecular features that might promote parallel genetic evolution

Summary

Introduction

Adaptation is a product of genetic modification and natural selection imposed by environmental challenges. Many studies of beneficial mutations, stop short of elucidating the exact molecular mechanisms connecting genotypic changes to phenotypic adaptation [11,12,13]. The lack of this level of information has rendered prediction of fitness effects, epistasis, and G6E interactions elusive. Much of our current knowledge of biological systems has come from studying phenotypes of deleterious gene knockouts Such approaches have uncovered many gene functions and genetic interactions but provided little information about the quantitative response of biological networks to environmental or genetic perturbations as well as the functional significance of a gene in the context of adaptation. A complementary approach to studying the function and evolution of biological systems, is to characterize molecular mechanisms through which beneficial mutations alter physiology, and reciprocally, how physiological differences due to genetic backgrounds or environments influence the effects of beneficial mutations

Methods

Results

Conclusion