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

Abstract

The Mexican cavefish, Astyanax mexicanus, is a captivating model for probing cave adaptations, showcasing pronounced divergence in traits like vision, brain morphology, behaviour, pigmentation, and hypoxia tolerance compared to its surface-dwelling counterpart. Very few protein-coding variants are identified in cave-morphs, and the vast phenotypic gap between the two morphs remains inadequately explained. We investigated the noncoding genomes of teleosts and found that 3,343 conserved non-coding elements (CNEs) were independently lost in cave-morphs. These CNEs, confirmed in Zebrafish, displayed enhancer-associated 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, these flanking genes were gradually downregulated during embryonic development of cave-morphs, contrasting with surface morphs. These insights underscore how compromised developmental pathways, stemming from the loss of distal regulatory elements, contribute to the regression of phenotypes in cave morphs. Article SummaryDespite availability of genome sequences and allied datasets, the genetic underpinning of regressed traits of cavefish remains enigmatic. By aligning the genome sequences of teleosts, we identified thousands of noncoding elements specifically lost in cavefish, exhibited enhancer-associated hallmarks, and were enriched with the binding sites of neuronal transcription factors. Their cognate genes were associated with eye and nervous system development, and exhibited developmental downregulation in cavefish. This study highlights how the loss of regulatory elements impacted the cavefish evolution and adaptation.