Abstract
BACKGROUND: Body size is a critical trait that influences an animal's physiology, behavior, and ecology. However, the molecular mechanisms underlying its evolution remain poorly understood, particularly in snakes. Snakes exhibit an extremely wide range of body sizes and strong ecological adaptability. Among snake species, the maximum body mass exceeds the minimum by over 200,000-fold, while the maximum body length surpasses the minimum by more than 110-fold. RESULTS: Through phylogenomic and comparative genomic analyses of 26 snake genomes, we identified 77 body size-associated genes (BSAGs) related to body length or body mass, highlighting key genetic drivers of body size evolution. Functional enrichment analyses revealed that metabolic pathways, particularly fatty acid metabolism and oxidoreductase activity, underwent significant expansion and positive selection, suggesting metabolic adaptations crucial for meeting the energetic demands of increased body size. Immune system-related genes, including those involved in antigen processing and presentation, similarly showed signatures of expansion and adaptive evolution, highlighting strengthened immune defenses in large-bodied snakes. Additionally, key candidate genes, such as YAP1, PLAG1, MGAT1 and SPRY1, exhibited both strong selection signals and correlation signals, and are functionally involved in developmental pathways critical for growth regulation. CONCLUSIONS: Our findings reveal a complex interplay of sensory, immune, metabolic, and growth-related genetic adaptations driving large body size evolution in snakes. This study provides novel insights into the molecular underpinnings of snake body size diversification and advances our understanding of their evolutionary history.