Members of the FET protein family (FUS, EWS and TAF15) are RNA- and DNA-binding proteins that have several roles in cells. They regulate gene expression at many levels, maintain mRNA stability and form stress granules. Primarily, FET proteins can be found in the nucleus, but they can also be transported into the cytoplasm. All FET proteins have the same domain architecture and previous bioinformatic analyses showed that they all possess a prion-like domain. Mutations in FET proteins have been linked to some neurodegenerative diseases, making them an important research topic. The most common pathology seen in patients are cytoplasmic protein aggregates, which can result in a toxic gain of function or loss of FET proteins' normal function. In this work we analysed the FET protein family with different bioinformatic tools. Phylogenetic analyses revealed how the proteins had evolved in mammals and we compared the results with the evolution of mammalian species. We showed that the phylogenetic relationships of individual FUS, EWS and TAF15 mostly match the evolution of mammalian species. We tried to expand the evolution analysis of FUS to vertebrates, however the bootstrap values were too low to allow reliable interpretation of the evolutionary relationships. We discovered that the genes encoding FET proteins had duplicated prior to diversification of mammalian species. We also analysed the conservation of the EWS QGSY domain within vertebrates and confirmed that tyrosine is the most conserved compared to other amino acids of similar frequency within the domain. Along with tyrosine, glutamine was shown to also be frequently conserved. The analysis of amino acid conservation within the QGSY domain could be further expanded to include the other proteins of the FET family.
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