title: Plasticity and epistasis strongly affect bacterial fitness after losing multiple metabolic genes.
abstract: Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epistasis on the fitness of Escherichia coli genotypes from whose genome biosynthetic genes for one, two, or three different amino acids have been deleted. Competitive fitness experiments between auxotrophic mutants and prototrophic wild-type cells in one of two carbon environments revealed that plasticity and epistasis strongly affected the mutants' fitness individually and interactively. Positive and negative epistatic interactions were prevalent, yet on average cancelled each other out. Moreover, epistasis correlated negatively with the expected effects of combined auxotrophy-causing mutations, thus producing a pattern of diminishing returns. Moreover, computationally analyzing 1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co-occurred significantly more often than expected by chance, suggesting epistatic interactions and/or environmental factors favored these combinations. Our results demonstrate that both the genetic background and environmental conditions determine the adaptive value of a loss-of-biochemical-function mutation and that fitness gains decelerate, as more biochemical functions are lost.
authors.affiliation: Experimental Ecology and Evolution Research Group, Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, 07745, Jena, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: Experimental Ecology and Evolution Research Group, Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, 07745, Jena, Germany.|Research Group Theoretical Systems Biology, Friedrich Schiller University of Jena, 07743, Jena, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Waschina
authors.affiliation: Research Group Theoretical Systems Biology, Friedrich Schiller University of Jena, 07743, Jena, Germany.|Research Group Medical Systems Biology, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, 24105, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaleta
authors.affiliation: Experimental Ecology and Evolution Research Group, Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, 07745, Jena, Germany. christiankost@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Kost
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D004843:Epistasis, Genetic; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D056084:Genetic Fitness; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation
chemical_list: D000596:Amino Acids; D029968:Escherichia coli Proteins
keywords: Adaptive gene loss; amino acid auxotrophy; black queen hypothesis; epistasis; phenotypic plasticity