RT Journal Article
SR Electronic
T1 Global epistasis emerges from a generic model of a complex trait
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.14.150946
DO 10.1101/2020.06.14.150946
A1 Gautam Reddy
A1 Michael M. Desai
YR 2020
UL http://biorxiv.org/content/early/2020/11/09/2020.06.14.150946.abstract
AB Epistasis between mutations can make adaptation contingent on evolutionary history. Yet despite widespread “microscopic” epistasis between the mutations involved, microbial evolution experiments show consistent patterns of fitness increase between replicate lines. Recent work shows that this consistency is driven in part by global patterns of diminishing-returns and increasing-costs epistasis, which make mutations systematically less beneficial (or more deleterious) on fitter genetic backgrounds. However, the mechanistic basis of this “global” epistasis remains unknown. Here we show that diminishing-returns and increasing-costs epistasis emerge generically as a consequence of pervasive microscopic epistasis. Our model predicts a specific quantitative relationship between the magnitude of global epistasis and the stochastic effects of microscopic epistasis, which we confirm by re-analyzing existing data. We further show that the distribution of fitness effects takes on a universal form when epistasis is widespread, and introduce a novel fitness landscape model to show how phenotypic evolution can be repeatable despite sequence-level stochasticity.Competing Interest StatementThe authors have declared no competing interest.