Insights into the evolution and domain structure of Ataxin-2 proteins across eukaryotes

Ataxin-2 is an evolutionarily conserved protein first identified in humans as responsible for spinocerebellar ataxia type 2 (SCA2). The molecular basis of SCA2 is the expansion of a polyglutamine tract in Ataxin-2, encoding a Lsm domain that may bind RNA and a PAM2 motif that enables interaction with the poly (A) binding protein. Although the association with SCA2 has been verified, a detailed molecular function for Ataxin-2 has not been established.

We have undertaken a survey of Ataxin-2 proteins across all eukaryotic domains. In eukaryotes, except for vertebrates and land plants, a single ortholog was identified. Notably, with the exception of birds, two Ataxin-2 genes exist in vertebrates. Expansion was observed in land plants and a novel class lacking the LsmAD domain was identified. Large polyQ tracts appear limited to primates and insects of the orders Hymenoptera and Diptera. A common feature across Ataxin-2 orthologs is the presence of proline-rich motifs, formerly described in the human protein.

Our analysis provides valuable information on the evolution and domain structure of Ataxin-2 proteins. Proline-rich motifs that may mediate protein interactions are widespread in Ataxin-2 proteins, but expansion of polyglutamine tracts associated with spinocerebellar ataxia type 2, is present only in primates, as well as some insects. Our analysis of Ataxin-2 proteins provides also a source to examine orthologs in a number of different species.