Sex chromosome stability and turnover across vertebrates: a developmental gene regulatory network perspective

Abstract

Sex chromosomes have evolved repeatedly across the Tree of Life, yet their evolutionary fates differ strikingly. In sharp contrast to mammals and birds with degenerated, stable Y/W chromosomes, in most amphibians, teleosts, non avian reptiles and flowering plants, sex chromosomes remain largely homomorphic and undergo frequently turnover. Explanations such as the evolutionary trap hypothesis, sexually antagonistic selection, mutation load, genetic drift and selfish genetic elements, focus on population genetic processes and do not fully explain this pattern. Here we propose the developmental gene regulatory network (GRN) lock in hypothesis. We compile case studies of turnover across vertebrates, synthesise comparative developmental data on sex determination and dosage regulation (DC). In mammals and birds, sex is determined by an early, initiation by somatic cells, fully penetrant master signal acting within a narrow, thermally buffered embryonic window. This signal operates within highly canalised GRNs, coupled to chromosome scale dosage compensation, with alternative splicing events playing little or no causal role in primary sex determination. This configuration makes it difficult for new master sex determining loci to invade without generating deleterious intermediate states. By contrast, many ectothermic vertebrates possess flexible, integrative threshold GRNs in which genetic, germ cells and environmental inputs interact over a prolonged sensitive embryonic period, with absent or largely gene-by-gene based DC and environmentally responsive splicing near key regulatory nodes, providing many entry points for sex determining loci to evolve. We outline empirical predictions and highlight how integrating developmental biology, molecular mechanisms and population genetics can yield testable models for when sex chromosomes become evolutionarily locked-in versus repeated turnover.