Antimicrobial peptides (AMPs) are a diverse group of molecules with potent, broad-spectrum activities against microbes. AMPs are found in a wide range of invertebrate and vertebrate organisms, representing an ancient form of innate immunity. Defensins and cathelicidins are two major families of AMPs in birds. With a key role in host defense against rapidly evolving pathogens, defensins and cathelicidins provide an ideal system for studying adaptive molecular evolution. Recent release of whole-genome sequences for various bird species enabled us to perform a comprehensive evolutionary analysis of avian AMPs across multiple bird lineages.
We mined 53 avian genomes representing 32 orders and identified 758 AMP genes, including 714 β-defensins and 44 cathelicidins. Both gene families form a generally conserved gene cluster in avian genomes, with certain genes being more prone to duplication or pseudogenisation events. Intense negative selection was detected in most of examined gene domains, likely accounting for the conservation of certain amino acid residues that are essential for the functioning of β-defensins and cathelicidins in birds. Episodic positive selection also played an important role in driving the diversification of certain peptide residues, contributing to high variability of gene sequences and electrostatic property of the peptides. Our results also revealed that selection may have acted on cathelicidins to maintain a balanced charge between the propiece and mature peptide domains, so that the high cationicity of the mature peptide is neutralised by the negative charge of the propiece before peptide secretion.
These findings greatly improved our understanding of the molecular evolution of avian AMPs and will be useful for understanding their role in the avian immune system. Additionally, the large dataset of defensin and cathelicidin peptides also provides a valuable resource for translational research and development of novel antimicrobial agents in the future.