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

Understanding the processes that link genotype to phenotype is a central challenge in
biology. Despite progress in discovering genes associated with ecologically relevant traits,
a poor understanding of the processes and functions via which molecules mediate
evolutionary differences leaves us critically far from linking proximate and ultimate causes
of evolution. This knowledge-gap is particularly large in multifaceted phenotypes of
ecological relevance such as life-histories where multiple traits covary and influence
fitness. In Atlantic salmon (Salmo salar), variation in a key life-history trait, maturation
age, is linked to the transcription cofactor vestigial-like 3 (vgll3). Here we show that despite
this simple genetic architecture, vgll3 genotype influences maturation age through a
complex regulatory mechanism whereby it controls the expression of diverse pubertal
signaling pathways. Using a multiomic approach in salmon testes, we show that the vgll3
genotype conferring early maturity upregulates key genes controlling androgen
production, cellular energy and adiposity, and TGF-β signaling, thereby increasing the
likelihood of earlier pubertal initiation. By mapping VGLL3 regulatory elements we further
show its interaction with distinct transcription factors in a genotype-dependent manner,
thus coordinating differential activation of regulatory pathways. This study reveals the
proximate mechanisms through which a genetically simple association leads to functionally
complex molecular differences in a spectrum of cellular traits, thus explaining the
molecular basis of pleiotropy in a large-effect gene. Our results indicate that evolution in
correlated phenotypes, as exemplified by alternative life-history strategies, can be dictated
by the function of major life-history genes.