Comparative Genomic Screening Identifies Developmental Constraint Loci Underscoring the Phenotypic Evolution of Syngnathids.

Seahorses and their relatives (syngnathids) exhibit remarkable diversity in morphology and function, characterized by their distinctive body shapes and specialized feeding mechanisms. Despite recent advances in uncovering the genetic basis of some traits, the genotype-phenotype map in syngnathids remains incomplete. In this study, we employed forward-genomic approaches and developed a method to enrich for human disease amino acid loci at a genomic scale. Our aim was to identify genetic loci associated with fin size reduction, tooth loss, and spinal curvature in syngnathids. Intriguingly, we identified a convergent amino acid change in the lat4a gene shared by syngnathids and some flying fishes, with in vitro analysis confirming its role in fin size evolution in both lineages. While genes critical for tooth development are conserved in syngnathids, the absence of key regulatory elements, such as pitx2, likely contributes to tooth loss. Additionally, we implicated col6a3 in spinal curvature development in seadragons. These findings reveal novel genetic signatures and developmental constraints underlying syngnathid diversity, demonstrating the utility of comparative genomics and targeted gene enrichment in exploring vertebrate evolution.