Discovery and classification of new reptile cathelicidins by genome mining: study of their structure and genomic organization in Testudines and Squamata

Cathelicidins, a diverse family of host defence peptides (HDPs) in vertebrates, are recognized for their potential in combating resistant microorganisms and their varied biological functions. While extensive studies have focused on mammalian cathelicidins, those in reptiles remain largely unexplored. In this study, we conducted a genome mining analysis that identified 287 cathelicidin genes across reptilian orders Testudines and Squamata. Of these genes, we identified 219 complete cathelicidin protein sequences and 68 cathelicidin-like gene copies that appear to be pseudogenes or gene fragments lacking intact open reading frames. We established for the first time a classification for reptile cathelicidins of the cited orders based on their sequence and structure, observing six types for Testudines and six for Squamata, suggesting a common ancestral lineage. Furthermore, we investigated the genomic arrangement of these cathelicidin genes, uncovering that they are grouped into clusters with variability in the gene number and in their organization. Cathelicidin derived mature peptides were classified into nine groups based on their sequences and physicochemical properties. This comprehensive study enhances the understanding of the cathelicidin family in reptiles, clarifying their genomic organization and describing the different types present. These classifications pave the way for future studies on the functions and specialization of each identified cathelicidin group. Moreover, they enable potential structure-activity studies of the peptides, establishing a foundation for differentiating their key features.