A complex mechanism translating variation of a simple genetic architecture into alternative life-histories

Abstract

Linking genes to traits is a central goal in biology. Despite progress in discovering genes associated with trait differences, a poor understanding of the functional mechanisms underlying genetic associations leaves us critically far from connecting genetic and phenotypic variation. This knowledge-gap is particularly large in multifaceted phenotypes of ecological relevance such as life-history traits. Using a multiomic dissection of the genotype-phenotype association in a large-effect maturation age gene - the transcription cofactor vestigial-like 3 (vgll3) - in Atlantic salmon (Salmo salar), we show that vgll3 mediates concerted changes of distinct molecular phenotypes associated with puberty in male gonads. Vgll3 genotype conferring early maturity upregulates key genes controlling androgen production, cellular energy and adiposity, and TGF-{beta} signaling, among others, thereby increasing the likelihood of earlier pubertal initiation. Genotype-dependent developmental trajectories are produced through VGLL3 interaction with distinct transcription factors, thus coordinating differential activation of regulatory pathways. These results reveal a genetically simple, yet functionally complex, architecture underlying alternative life-histories where variation in a single major effect gene produces pleiotropic variation in a spectrum of cellular traits. Our results further suggest that evolution in correlated phenotypes such as exemplified by alternative life history strategies may be mediated by a surprisingly simple genetic architecture.