More Than the Sum of Its Parts: A Complex Epistatic Network Underlies Natural Variation in Thermal Preference Behavior in Caenorhabditis elegans

Behavior is a complex trait that results from interactions among multiple genes and the environment. Both additive and nonadditive effects are expected to contribute to broad-sense heritability of complex phenotypes, although the relative contribution of each of these mechanisms is unknown. Here, we mapped genetic variation in the correlated phenotypes of thermal preference and isothermal dispersion in the nematode Caenorhabditis elegans. Genetic variation underlying these traits is characterized by a set of linked quantitative trait loci (QTL) that interact in a complex epistatic network. In particular, two loci located on the X chromosome interact with one another to generate extreme thermophilic behavior and are responsible for ∼50% of the total variation observed in a cross between two parental lines, even though these loci individually explain very little of the among-line variation. Our results demonstrate that simultaneously considering the influence of a quantitative trait locus (QTL) on multiple scales of behavior can inform the physiological mechanism of the QTL and show that epistasis can explain significant proportions of otherwise unattributed variance within populations.