title: Assessing functional divergence in EF-1alpha and its paralogs in eukaryotes and archaebacteria.
abstract: A number of methods have recently been published that use phylogenetic information extracted from large multiple sequence alignments to detect sites that have changed properties in related protein families. In this study we use such methods to assess functional divergence between eukaryotic EF-1alpha (eEF-1alpha), archaebacterial EF-1alpha (aEF-1alpha) and two eukaryote-specific EF-1alpha paralogs-eukaryotic release factor 3 (eRF3) and Hsp70 subfamily B suppressor 1 (HBS1). Overall, the evolutionary modes of aEF-1alpha, HBS1 and eRF3 appear to significantly differ from that of eEF-1alpha. However, functionally divergent (FD) sites detected between aEF-1alpha and eEF-1alpha only weakly overlap with sites implicated as putative EF-1beta or aminoacyl-tRNA (aa-tRNA) binding residues in EF-1alpha, as expected based on the shared ancestral primary translational functions of these two orthologs. In contrast, FD sites detected between eEF-1alpha and its paralogs significantly overlap with the putative EF-1beta and/or aa-tRNA binding sites in EF-1alpha. In eRF3 and HBS1, these sites appear to be released from functional constraints, indicating that they bind neither eEF-1beta nor aa-tRNA. These results are consistent with experimental observations that eRF3 does not bind to aa-tRNA, but do not support the 'EF-1alpha-like' function recently proposed for HBS1. We re-assess the available genetic data for HBS1 in light of our analyses, and propose that this protein may function in stop codon-independent peptide release.
authors.affiliation: Program in Evolutionary Biology, Canadian Institute for Advanced Research and Genome Atlantic, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada. yinagai@dal.ca
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Christian
authors.initials: C
authors.lastname: Blouin
authors.forename: Edward
authors.initials: E
authors.lastname: Susko
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001105:Archaea / Q000235:genetics; D001419:Bacteria / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004023:Dictyostelium / Q000235:genetics; D016828:Diplomonadida / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D014644:Genetic Variation; D016829:Giardia lamblia / Q000235:genetics; D008969:Molecular Sequence Data; D020648:Peptide Elongation Factor 1 / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014246:Trichomonas vaginalis / Q000235:genetics; D014346:Trypanosoma brucei brucei / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D016054:DNA, Protozoan; D020648:Peptide Elongation Factor 1