Dynamic evolution of the MutS family in animals: multiple losses of MSH paralogues and gain of a viral MutS homologue in octocorals

MutS is a key component of the Mismatch Repair (MMR) pathway. Members of the MutS family of proteins are present in bacteria, archaea, eukaryotes, and viruses. Six MutS homologues (MSH1-6), have been identified in yeast, three of which function in nuclear MMR, while MSH1 has been associated with mitochondrial DNA repair. MSH1 is believed to be lacking in animals, potentially reflecting the loss of MMR in animal mitochondria, and correlated with higher rates of mitochondrial sequence evolution. An intriguing exception has been found in octocorals, a group of marine animals from phylum Cnidaria, which encode a MutS-homologue (mtMutS) in their mitochondrial genome. It has been suggested that this protein functions in mitochondrial DNA repair, which would explain some of the lowest rates of mitochondrial sequence evolution observed in this group. To place the acquisition of mtMutS in a functional context, we investigated the evolution of the whole MutS family in animals. Our study confirmed the acquisition of octocoral mtMutS by horizontal gene transfer from a giant virus. Surprisingly, we found orthologues of yeast MSH1 in all hexacorals (the sister group of octocorals) and several sponges and placozoans. By contrast, MSH1 orthologues were lacking in octocorals, medusozoan cnidarians, ctenophores, and bilaterian animals. Furthermore, while we were able to identify MSH2 and MSH6 in all animals, MSH4, MSH5, and, especially, MSH3 were missing in multiple species. Overall, our analysis reveals a dynamic evolution of MSH family in animals, with multiple losses of MSH1, MSH3, some losses of MSH4 and MSH5, and a gain of octocoral mtMutS.