title: Diminishing returns epistasis among beneficial mutations decelerates adaptation.
abstract: Epistasis has substantial impacts on evolution, in particular, the rate of adaptation. We generated combinations of beneficial mutations that arose in a lineage during rapid adaptation of a bacterium whose growth depended on a newly introduced metabolic pathway. The proportional selective benefit for three of the four loci consistently decreased when they were introduced onto more fit backgrounds. These three alleles all reduced morphological defects caused by expression of the foreign pathway. A simple theoretical model segregating the apparent contribution of individual alleles to benefits and costs effectively predicted the interactions between them. These results provide the first evidence that patterns of epistasis may differ for within- and between-gene interactions during adaptation and that diminishing returns epistasis contributes to the consistent observation of decelerating fitness gains during adaptation.
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Chou
authors.forename: Hsuan-Chao
authors.initials: HC
authors.lastname: Chiu
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Delaney
authors.forename: Daniel
authors.initials: D
authors.lastname: Segrè
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Marx
mesh_terms: D000222:Adaptation, Physiological; D000483:Alleles; D005075:Biological Evolution; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D056084:Genetic Fitness; D016680:Genome, Bacterial; D005978:Glutathione / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020601:Methylobacterium extorquens / Q000166:cytology / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008957:Models, Genetic; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D005978:Glutathione