High-order epistasis shapes evolutionary trajectories

PLoS Computational Biology
Zachary R Sailer, Zachary R Sailer

Abstract

High-order epistasis-where the effect of a mutation is determined by interactions with two or more other mutations-makes small, but detectable, contributions to genotype-fitness maps. While epistasis between pairs of mutations is known to be an important determinant of evolutionary trajectories, the evolutionary consequences of high-order epistasis remain poorly understood. To determine the effect of high-order epistasis on evolutionary trajectories, we computationally removed high-order epistasis from experimental genotype-fitness maps containing all binary combinations of five mutations. We then compared trajectories through maps both with and without high-order epistasis. We found that high-order epistasis strongly shapes the accessibility and probability of evolutionary trajectories. A closer analysis revealed that the magnitude of epistasis, not its order, predicts is effects on evolutionary trajectories. We further find that high-order epistasis makes it impossible to predict evolutionary trajectories from the individual and paired effects of mutations. We therefore conclude that high-order epistasis profoundly shapes evolutionary trajectories through genotype-fitness maps.

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Citations

Oct 21, 2017·Reports on Progress in Physics·Uri ObolskiLilach Hadany
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Zachary R Sailer, Michael J Harms
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Software Mentioned

scipy
Python
jupyter
learn
scikit
matplotlib
numpy

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