Project description:<p><strong>BACKGROUND:</strong> Reptiles exhibit a wide variety of skin colors, which serve essential roles in survival and reproduction. However, the molecular basis of these conspicuous colors remains unresolved.</p><p><strong>RESULTS:</strong> We investigate color morph-enriched Asian vine snakes (<em>Ahaetulla prasina</em>), to explore the mechanism underpinning color variations. Transmission electron microscopy imaging and metabolomics analysis indicates that chromatophore morphology (mainly iridophores) is the main basis for differences in skin color. Additionally, we assemble a 1.77 Gb high-quality chromosome-anchored genome of the snake. Genome-wide association study and RNA sequencing reveal a conservative amino acid substitution (p.P20S) in <em>SMARCE1</em>, which may be involved in the regulation of chromatophore development initiated from neural crest cells. <em>SMARCE1</em> knockdown in zebrafish and immunofluorescence verify the interactions among <em>SMARCE1</em>, iridophores, and <em>tfec</em>, which may determine color variations in the Asian vine snake.</p><p><strong>CONCLUSIONS:</strong> This study reveals the genetic associations of color variation in Asian vine snakes, providing insights and important resources for a deeper understanding of the molecular and genetic mechanisms related to reptilian coloration.</p>