Aerolysins and actinoporins are interesting representatives of toxins that form membrane pores. They are most prevalent in bacteria but are also found in vertebrates. A large increase in the number of genes that encode aerolysins and actinoporins has occurred in lampreys. The causes and mechanisms for such gene expansion, their evolution and diversity are not yet known. Using a variety of bioinformatics tools and phylogenomic analysis, I have obtained gene and protein sequences of aerolysins and actinoporins in lampreys and related organisms. Aerolysins and actinoporins underwent a large increase in the number of genes only in lampreys. Hagfishes, the closest relatives of lampreys have lost genes for aerolysins and actinoporins. Aerolysin genes are extremely conserved in lampreys (> 90\% nucleotide identity) and are quite similar to the zebrafish aerolysin Dln1. The mechanisms of their tandem duplications was gene duplication followed by concerted evolution and gene conversion. Increased number of aerosolysin genes in lampreys results in increased production of encoded proteins, which participate in the immune response and are cytolytic. I also analyzed the possible role of penelope retroelements on tandem duplications of aerolysins and found that they had no effect since they are not present in the vicinity of the aerolysin genes. In contrast to aerolysins, actinoporins are very divergent in lampreys and originated by numerous gene duplications followed by functional diversification. Due to their diversity, they are likely to act on different targets. By homologous modeling of 3D protein structures, I found that the lamprey aerolysins are structurally very similar to the zebrafish aerolysin Dln1 and probably have a similar mechanism of action. 3D structural models of actinoporins from lampreys and sea anemones, where actinoporines were first found, are very different, and also have a modified P-[WYF]-D membrane binding site. Analysis of aerolysin and actinoporin gene families in lampreys has provided a new insight on the origin, diversity and the biological role of the increased number of genes encoding these toxins in the oldest vertebrate lineage.
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