Interactions between epistasis and pleiotropy in generic models of complex traits
- 1Harvard University
Abstract
Evolution in fluctuating environments depends critically on epistatic interactions between mutations and the pleiotropic effects these mutations have on fitness across multiple conditions. However, while these effects of epistasis and pleiotropy have been extensively studied individually, the interactions between them are less well understood. In this study, we analyze how genetic background shapes the effects of mutations across multiple environmental conditions in generic models of complex traits. We show that when epistasis is widespread and random, systematic patterns of cross-environment pleiotropy can emerge naturally. Specifically we outline two regimes, widespread random epistasis (WRE) and structured pleiotropy (SP), in which patterns of global epistasis in one environment can be predicted from those in other conditions. We outline these predictions in several classes of generic null models, and test these predictions in laboratory budding yeast by measuring the fitness effects of a large set of mutations across many genetic backgrounds in several growth environments. We find that only a subset of mutations fall within the WRE and SP regimes, but that in these cases two of our models provide accurate fits to the data. Finally, we use this framework to show how modular, pleiotropic architectures shape long-term evolutionary steady states in fluctuating environments, revealing how tradeoffs between environments can develop from the geometry of shared latent interaction structure.
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BibTeX
@misc{brooks2026interactions,
title = {{Interactions between epistasis and pleiotropy in generic models of complex traits}},
author = {C. Brooks and M. Gupta and G. Reddy and M. M. Desai},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755220},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755220v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Interactions between epistasis and pleiotropy in generic models of complex traits
AU - C. Brooks
AU - M. Gupta
AU - G. Reddy
AU - M. M. Desai
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755220
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755220v1
AB - Evolution in fluctuating environments depends critically on epistatic interactions between mutations and the pleiotropic effects these mutations have on fitness across multiple conditions. However, while these effects of epistasis and pleiotropy have been extensively studied individually, the interactions between them are less well understood. In this study, we analyze how genetic background shapes the effects of mutations across multiple environmental conditions in generic models of complex traits. We show that when epistasis is widespread and random, systematic patterns of cross-environment pleiotropy can emerge naturally. Specifically we outline two regimes, widespread random epistasis (WRE) and structured pleiotropy (SP), in which patterns of global epistasis in one environment can be predicted from those in other conditions. We outline these predictions in several classes of generic null models, and test these predictions in laboratory budding yeast by measuring the fitness effects of a large set of mutations across many genetic backgrounds in several growth environments. We find that only a subset of mutations fall within the WRE and SP regimes, but that in these cases two of our models provide accurate fits to the data. Finally, we use this framework to show how modular, pleiotropic architectures shape long-term evolutionary steady states in fluctuating environments, revealing how tradeoffs between environments can develop from the geometry of shared latent interaction structure.
ER -