Higher-Order Interactions in Biology: The Curious Case of Epistasis

Abstract

As with other arenas of complex systems, the biological world is driven by interactions between actors, parcels, and forces of various kinds. Higher-order interactions between these elements defines the complexity underlying many biological systems, from species interactions, the microbiota, to biomechanics and others. Here we explore higher-order interactions through a discussion of epistasis, a cutting-edge concept in population and evolutionary genetics. We examine the concept’s history and controversies, measure higher-order epistasis operating in a gene encoding an enzyme, and discuss the implications of higher-order interactions for contemporary conversations surrounding genetic modification and other technical challenges that require a more refined understanding of the relationship between genotype and phenotype.