Universally conserved translation initiation factors

Abstract

The process by which translation is initiated has long been considered similar in Bacteria and Eukarya but accomplished by a different unrelated set of factors in the two cases. This not only implies separate evolutionary histories for the two but also implies that at the universal ancestor stage, a translation initiation mechanism either did not exist or was of a different nature than the extant processes. We demonstrate herein that (i) the "analogous" translation initiation factors IF-1 and eIF-1A are actually related in sequence, (ii) the "eukaryotic" translation factor SUI1 is universal in distribution, and (iii) the eukaryotic/archaeal translation factor eIF-5A is homologous to the bacterial translation factor EF-P. Thus, the rudiments of translation initiation would seem to have been present in the universal ancestor stage. However, significant development and refinement subsequently occurred independently on both the bacterial lineage and on the archaeal/eukaryotic line.

Figure 1

Multiple sequence alignment of bacterial IF-1, eukaryotic eIF-1A, and their archaeal homologs (aIF-1A). Positions in which sequence conservation is >50% identity are highlighted in black. The last line is a consensus of the six S1 motifs found in E. coli ribosomal protein S1: highlighted uppercase type denotes those residues that are also highly conserved in the IF-1/eIF-1A/aIF-1A family, whereas highlighted lowercase type denotes the residues for which a related amino acid occurs in the family. (Dots denote nonconserved positions in the S1 consensus, and dashes denote gaps/insertions of more than one residue.) The horizontal arrows display the positions of the β-strands according to the three-dimensional structure (33). Protein names (and accession number—when different) are as follows: IF1_ECOLI, E. coli IF-1; IF1-SYNEC, Synechocystis sp. IF-1 (EMBL:D90905_47); IF1_BACSU, Bacillus subtilis IF-1; IF1-DEIRA, unpublished ORF from Deinococcus radiodurans; IF1A_METJA, Methanococcus jannaschii aIF-1A; IF1A-METTH, Methanobacterium thermoautotrophicum unpublished ORF; IF1A-ARCFU, Archaeoglobus fulgidus unpublished ORF; YRP2_THEAC, Thermoplasma acidophilum hypothetical protein; IF1A_WHEAT, Triticum aestivum eIF-1A; IF1A_HUMAN, human eIF-1A; IF1A_RABIT, Oryctolagus cuniculus eIF-1A; IF1A_YEAST, Saccharomyces cerevisiae eIF-1A.

Figure 2

Multiple sequence alignment of the eukaryotic SUI1/eIF-1 protein family with their archaeal and bacterial homologs. Protein names (and accession number—when different) are as follows: YCIH_ECOLI, E. coli hypothetical protein; YCIH_SALTY, Salmonella typhimurium hypothetical protein; YCIH_HAEIN, Haemophilus influenzae hypothetical protein; YCIH-SYNEC, Synechocystis sp. hypothetical protein (European Molecular Biology Laboratory accession no. D64003_48); SUI1-METJA, M. jannaschii hypothetical ORF MJ0463 (Protein Information Resource accession no. G64357); YRP1_METVA, Methanococcus vannielii hypothetical protein; SUI1-METTH, M. thermoautotrophicum unpublished ORF; SUI1-ARCFU, A. fulgidus unpublished ORF; SUI1_HUMAN, human SUI1; SUI1_ANOGA, Anopheles gambiae SUI1; SUI1_YEAST, Saccharomyces cerevisiae SUI1; SUI1_ARATH, Arabidopsis thaliana SUI1.

Figure 3

Multiple sequence alignment of the eukaryotic translation initiation eIF-5A protein family with their archaeal homologs and the bacterial translation elongation EF-P family. The minimum domain of eukaryotic IF-5A needed for hypusine modification (51) is boxed; the asterisk denotes the lysine residue that is posttranslationally modified to hypusine. Protein names (and accession number—when different) are as follows: IF5A_METJA, M. jannaschii aIF-5A; IF5A-METTH, M. thermoautotrophicum unpublished ORF; IF5A-ARCFU, A. fulgidus unpublished ORF; IF5A_SULAC, Sulfolobus acidocaldarius aIF-5A; IF5A_HUMAN, human eIF-5A; IF5A_DICDI, Dictyostelium discoideum eIF-5A; IF51_YEAST, S. cerevisiae eIF-5A; IF52_CAEEL, Caenorhabditis elegans eIF-5A; EFP_BACSU, B. subtilis EF-P; EFP_SYNY3, Synechocystis sp. EF-P; EFP_ECOLI, E. coli EF-P; EFP_HELPY, Helicobacter pylori EF-P.