TY - JOUR AU1 - Domingo, Júlia AU2 - Diss, Guillaume AU3 - Lehner, Ben AB - A central question in genetics and evolution is the extent to which the outcomes of mutations change depending on the genetic context in which they occur 1–3 . Pairwise interactions between mutations have been systematically mapped within 4–18 and between 19 genes, and have been shown to contribute substantially to phenotypic variation among individuals 20 . However, the extent to which genetic interactions themselves are stable or dynamic across genotypes is unclear 21, 22 . Here we quantify more than 45,000 genetic interactions between the same 87 pairs of mutations across more than 500 closely related genotypes of a yeast tRNA. Notably, all pairs of mutations interacted in at least 9% of genetic backgrounds and all pairs switched from interacting positively to interacting negatively in different genotypes (false discovery rate < 0.1). Higher-order interactions are also abundant and dynamic across genotypes. The epistasis in this tRNA means that all individual mutations switch from detrimental to beneficial, even in closely related genotypes. As a consequence, accurate genetic prediction requires mutation effects to be measured across different genetic backgrounds and the use of  higher-order epistatic terms. TI - Pairwise and higher-order genetic interactions during the evolution of a tRNA JF - Nature DO - 10.1038/s41586-018-0170-7 DA - 2018-05-30 UR - https://www.deepdyve.com/lp/springer-journals/pairwise-and-higher-order-genetic-interactions-during-the-evolution-of-3XIXHx4mZE SP - 117 EP - 121 VL - 558 IS - 7708 DP - DeepDyve ER -