Global epistasis emerges from a generic model of a complex trait

Epistasis between mutations can make adaptation contingent on evolutionary history. Yet despite widespread ‘microscopic’ epistasis the involved, microbial evolution experiments show consistent patterns of fitness increase replicate lines. Recent work shows that this consistency is driven in part by global diminishing-returns and increasing-costs epistasis, which systematically less beneficial (or more deleterious) fitter genetic backgrounds. However, origin ‘global’ remains unknown. Here, we emerge generically as a consequence pervasive microscopic epistasis. Our model predicts specific quantitative relationship magnitude stochastic effects confirm reanalyzing existing data. We further distribution takes universal form when introduce novel landscape to how phenotypic be repeatable sequence-level stochasticity.