Loss of conserved noncoding elements likely shaped the evolution of regressed phenotypes in cavefish

The Mexican cavefish, Astyanax mexicanus, is a captivating model for probing cave adaptations, showcasing pronounced divergence in traits like vision, brain morphology, behaviour, pigmentation, metabolism and hypoxia tolerance compared to its surface-dwelling counterpart. However, only a small number of protein-coding variants have been found in cave-morphs, leaving the vast phenotypic gap between the two morphs largely unexplained. We aligned the genomes of five closely related teleosts and identified 46914 conserved noncoding elements (CNEs), of which 473 were specifically lost in cave-morphs. These CNEs, confirmed in Zebrafish, displayed activating histone modifications, possessed binding sites of neuronal transcription factors and interacted with cognate genes through chromatin loops. Genes crucial for eye and nervous system development were located adjacent to CNEs lost in cave morphs. Notably, the flanking genes were gradually downregulated during embryonic development of cave-morphs, contrasting with surface morphs. These insights underscore how dampened developmental pathways, stemming from the loss of distal regulatory elements, may have contributed to the evolutionary regression of phenotypes in cave morphs.