Fig 2. Diverse evolutionary dynamics of CLCA genes.
In chicken and mammals, all CLCA genes are conserved in a single locus, flanked by the ODF2L and SH3GBL1 genes (upper panel). In chickens, only two CLCA genes, CLCA1 and CLCA2, are found within this locus with no other CLCA-related genes throughout the genome. According to the phylogenetic pattern, CLCA2 seems highly conserved, with a single intact representative in each mammal examined. In contrast, the ancestor of another vertebrate CLCA gene has apparently undergone two independent duplications in early mammalian evolution, resulting in CLCA1, CLCA3, and CLCA4, but it remained as a single copy in chicken. While CLCA1 is present as a single intact copy in all mammalian species examined and chicken, CLCA3 and CLCA4 underwent further duplication or inactivation (*) events in select mammalian branches (lower panel). As the nomenclature of CLCA genes is still inconsistent, in particular for duplicated genes, we followed the current designations used in the GenBank database with the exception of bovine unidentified gene LOC784768 which we here termed CLCAx for the ease of understanding (S1 Table).