Cathelicidins Revisited: Molecular Evolution, Structure and Functional Implications

Pavlopoulou A.

International Journal of Systems Biology and Biomedical Technologies (IJSBBT), vol.2, no.2, pp.8-32, 2013 (Peer-Reviewed Journal)


Cathelicidins constitute important antimicrobial peptides of innate immunity. In order to elucidate the evolutionary history of cathelicidins, the author performed comprehensive phylogenetic analyses of cathelicidin homologs in all available genomes including those completed recently. The organization of cathelicidin genes, as well as the secondary and tertiary structures of the inferred proteins are conserved. Based on integrated genomic, structural, and functional data, the author identified the last common ancestor of the cathelicidin family in lampreys, thus tracing the evolutionary origin of cathelicidins 550 million years ago. The author’s data suggest that cathelicidins arose concordantly with the adaptive immune system, a new organismal function first acquired in lampreys. The appearance of cathelicidins at the junction of innate and adaptive immunity may explain their dual roles as signal transducing molecules and as antimicrobial peptide precursors. Conserved regulatory elements associated with functions of the immune system were identified in cathelicidin gene promoter sequences invariably from fishes to humans.