Comparative genomics reveals candidate genomic signatures of multi-lineage convergent adaptation in semi-aquatic mammals

Secondary aquatic adaptation is an important topic in the study of adaptive evolution in animals. Semi-aquatic mammals have arisen independently multiple times within Mammalia. They have retained some traits associated with terrestrial life while also evolving morphological, physiological, and behavioral traits related to aquatic habitats. They therefore provide an ideal model for exploring the molecular mechanisms underlying adaptation during complex ecological transitions. Previous studies have provided important insights into the genomic basis of adaptation in several semi-aquatic mammals and related semi-aquatic lineages. However, a genome-wide framework for systematically comparing shared adaptive signatures across multiple independently evolved semi-aquatic mammalian lineages remains relatively limited. We performed a genome-wide comparative analysis of high quality genomes from 31 mammalian species representing 18 orders, including nine semi-aquatic taxa from five orders. Gene family analyses showed that expanded gene families associated with semi-aquatic lineages were recurrently enriched for immune related functions across multiple independent orders. We further identified 24 positively selected genes, 122 rapidly evolving genes, 17 semi-aquatic lifestyle associated genes, and 1 convergent amino acid substitution site. These candidate genomic signals were mainly related to sensory and nervous processes, energy metabolism and thermoregulation, hypoxia response and DNA repair, and immune function. Representative candidates included SCN11A , CRB2 , and NEUROD1 , which are associated with sensory and neural processes, LEP , CKMT2 , and SLC25A25 , which are involved in energy metabolism and thermoregulation, ADORA2B , CYBB , and BRCA1 , which are related to hypoxia response, oxidative stress, and DNA repair, and MHC-DMB , CD3D , and IL4R , which are associated with immune processes. Our study identified candidate genomic signals associated with the semi-aquatic lifestyle across multiple functional systems, including sensory and neural processes, energy metabolism and thermoregulation, hypoxia response and DNA repair, and immune function. Similarities among independently evolved semi-aquatic lineages were observed in amino acid substitution, gene evolutionary rates, and recurrent functional enrichment patterns across orders. These findings provide genome-wide hypotheses regarding potentially shared molecular processes involved in semi-aquatic adaptation, although the biological roles of the identified candidates and functional processes require further validation.