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

• 成果类型: Article
• 署名作者: Verta, Jukka- Pekka; Moustakas-Verho, Jacqueline E.; Donner, Iikki; Frapin, Morgane; Ruokolainen, Annukka; Debes, Paul, V; Erkinaro, Jaakko; Primmer, Craig R.
• 署名单位: University of Helsinki; Nord University; Natural Resources Institute Finland (Luke); University of Helsinki
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12989
• DOI: 10.1073/pnas.2402386121
• 发表日期: 2024-11-26
• 关键词: rna-seq data; steroidogenic factor-1; transcription factors; knockout mice; locus; AGE; sticklebacks; expression; EVOLUTION; maturity

摘要

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-beta 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.