Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Evolution of the Translational GTPase Superfamily
The ancient translational GTPase (trGTPase) superfamily includes a number of essential proteins, some of which originated before the last common ancestor of all life (LUCA). These GTP hydrolyzing enzymes function in a variety of cellular processes including core roles in the four stages of protein synthesis: initiation, elongation, termination, and ribosome recycling. Bioinformatic analyses of trGTPases have shed light on their evolution at a variety of levels, providing a framework for understanding the functional evolution of these proteins.
All trGTPases are defined by the presence of a highly conserved GTPase (G) domain together with one or more family- and/or subfamily-specific domains. This shared G domain allows the phylogenetic relationships among diverse GTPases to be estimated. Previous analyses of P-loop GTPases and ATPases identified four universal and therefore pre-LUCA families in the trGTPase class: EF1, EF2, SelB, and IF2 (1). We have conducted in depth phylogenetic analyses of these trGTPases, using a universal alignment of the G domain from a broad sampling of organisms across the tree of life. Within this, we have identified 27 distinct trGTPase subfamilies that group together into three major families: IF2, EF2, and EF1S (comprising EF1 and SelB) based on phylogenies, domain architecture, and conserved indels (Fig. 1). The superfamily phylogeny has been used to organize a relational database of trGTPases and their attributes, publicly accessible via an online interface (www.trGTPbase.org.uk).
The database and superfamily phylogeny have been used as a starting point for finer scale analyses of various subfamilies. Phylogenetic and genomic context analyses of the elongation factor EF-G subfamily reveal multiple forms that exist in parallel to the slowly evolving form found in most bacteria and encoded in the str operon (strEFG) (2). Surprisingly, the two mitochondrial EF-Gs are deep paralogs that associate with EF-Gs from a sporadic taxonomic distribution of bacteria, being found in spirochetes, delta-proteobacteria, and planctomycetes. This suggests that the genes encoding these proteins may have experienced multiple lateral transfers, including to the bacterial lineage that gave rise to mitochondria. Unusual patterns are also found for the EF-G of the other endosymbiotic eukaryotic organelle, the chloroplast, which apparently uses an alpha-proteobacterial derived EF-G rather than the expected cyanobacterial form. The persistence of EF-G duplicates suggests subfunctionalization, whereby paralogs perform only partially overlapping subsets of "canonical" EF-G activities (2).
Other trGTPases, specifically eRF3, Hbs1p, and Ski7p, play central roles in various mRNA surveillance mechanisms. These are nonsense mediated decay (NMD, eRF3), no-go decay (NGD, Hbs1p) and non-stop decay (NSD, Ski7p). We have analyzed the phylogenetic distribution and sequence conservation of these proteins and, in the case of eRF3 and Hbs1p, their binding partners, eRF1 and Dom34p, respectively. These analyses show that eRF1/Dom34p are universal in eukaryotes and archaea, while eRF3 and Hbs1p are restricted to, and almost universal in eukaryotes (the only exception being the absence of Hbs1p in some Apicomplexa). The Hbs1p paralog Ski7p appears to be limited to a subset of Saccharomyces species, derived from a duplication of Hbs1p in the Ascomycete lineage. This has allowed reconstruction of the evolution of these novel eukaryotic mRNA decay processes from translation termination mechanisms that were present in the common ancestor of eukaryotes and archaea (3).
Figure 1: Schematic diagram of the phylogenetic relationships among the major families of trGTPases. Subfamily names are coded by their taxonomic distribution as follows; green and underlined: bacteria, red and italic: eukaryotes, blue with names prefixed with e/a: subfamilies present in both eukaryotes and archaea.
References and Footnotes
Department of Systematic Biology