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 largely 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 up-regulates 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.

中文翻译：

---

一种将简单遗传结构的变异转化为替代生活史的复杂机制


了解将基因型与表型联系起来的过程是生物学的一个核心挑战。尽管在发现与生态相关特征相关的基因方面取得了进展，但对分子介导进化差异的过程和功能的理解不足，使我们严重无法将进化的直接原因和最终原因联系起来。这种知识差距在生态相关性的多方面表型中尤其大，例如多个性状协变并影响适应性的生活史。在大西洋鲑鱼 （ Salmo salar ） 中，关键生活史性状（成熟年龄）的变化在很大程度上与转录辅因子退化样 3 （vgll3） 有关。在这里，我们表明，尽管遗传结构简单，但 vgll3 基因型通过复杂的调节机制影响成熟年龄，从而控制不同青春期信号通路的表达。在鲑鱼睾丸中使用多组学方法，我们表明赋予早熟的 vgll3 基因型上调控制雄激素产生、细胞能量和肥胖以及 TGF β信号的关键基因，从而增加青春期提前开始的可能性。通过绘制 VGLL3 调节元件，我们进一步展示了它以基因型依赖性方式与不同转录因子的相互作用，从而协调调节途径的差异激活。这项研究揭示了遗传简单关联导致一系列细胞性状中功能复杂的分子差异的直接机制，从而解释了大效应基因中多效性的分子基础。 我们的结果表明，相关表型的进化，如替代生活史策略所举例，可以由主要生活史基因的功能决定。