Molecular evolution and functional divergence of eukaryotic translation initiation factor 2-alpha kinases

Eukaryotic translation initiation factor 2-alpha kinase (EIF2AK) proteins inhibit protein synthesis at translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock, and heat shock. Origin and functional diversification of EIF2AK sequences remain ambiguous. Here we determine the origin and molecular evolution of EIF2AK proteins in lower eukaryotes and studied the molecular basis of divergence among sub-family sequences. Present work emphasized primitive origin of EIF2AK4 sub-family gene in lower eukaryotes of protozoan lineage. Phylogenetic analysis supported common origin and sub-family based classification of EIF2AKs. Functional divergence studies across sub-families revealed several putative amino acid sites, which assist in altered protein interactions of kinase domains. The data can facilitate designing site-directed experimental studies aiming at elucidating diverse functional aspects of kinase domains regarding down-regulation of protein synthesis.