An Antagonistically Pleiotropic Gene Regulates Vertebrate Growth, Maturity and Aging

However, empirical evidence for these trade-offs in vertebrates remains scarce, particularly in the context of ecologically relevant life histories. Here, we identify vestigial-like 3 (vgll3), a transcription cofactor previously linked with age at maturity in humans and Atlantic salmon through GWAS studies, as an antagonistically pleiotropic gene in turquoise killifish (Nothobranchius furzeri).

By disrupting two conserved vgll3 isoforms, we show that reduction of vgll3, in an isoform- or dose-dependent manner, accelerated male growth and reproductive development. This indicates that vgll3 regulates male sexual maturity. However, early-life benefits come at a late-life cost, as older mutant males with a disrupted long isoform develop melanoma-like tumors, validated via transplantation into immunodeficient rag2 models, and exhibit increased age-related mortality rate.