TFAM detects co-evolution of tRNA identity rules with lateral transfer of histidyl-tRNA synthetase

Abstract

We present TFAM, an automated, statistical method to classify the identity of tRNAs. TFAM, currently optimized for bacteria, classifies initiator tRNAs and predicts the charging identity of both typical and atypical tRNAs such as suppressors with high confidence. We show statistical evidence for extensive variation in tRNA identity determinants among bacterial genomes due to variation in overall tDNA base content. With TFAM we have detected the first case of eukaryotic-like tRNA identity rules in bacteria. An α-proteobacterial clade encompassing Rhizobiales, Caulobacter crescentus and Silicibacter pomeroyi, unlike a sister clade containing the Rickettsiales, Zymomonas mobilis and Gluconobacter oxydans, uses the eukaryotic identity element A73 instead of the highly conserved prokaryotic element C73. We confirm divergence of bacterial histidylation rules by demonstrating perfect covariation of α-proteobacterial tRNAHis acceptor stems and residues in the motif IIb tRNA-binding pocket of their histidyl-tRNA synthetases (HisRS). Phylogenomic analysis supports lateral transfer of a eukaryotic-like HisRS into the α-proteobacteria followed by in situ adaptation of the bacterial tDNAHis and identity rule divergence. Our results demonstrate that TFAM is an effective tool for the bioinformatics, comparative genomics and evolutionary study of tRNA identity.

The requirement for the highly conserved G−1 residue of Saccharomyces cerevisiae tRNAHis can be circumvented by overexpression of tRNAHis and its synthetase

“…Since the G À1 residue is unique to tRNA His , there would be strong evolutionary pressure to maintain this recognition element once it had evolved. The other mechanism occurs in the clade of alphaproteobacteria in which the G À1 residue is not found, and in which the HisRS requires other recognition elements for tRNA charging (Ardell and Andersson 2006;Wang et al 2007). However, it remains possible that the G À1 residue has another role in the cell, and that recognition of this G À1 residue by HisRS evolved subsequently.…”

On the Evolution and Expression of Chlamydomonas reinhardtii Nucleus-Encoded Transfer RNA Genes

“…ac.jp/ and http:/ /dictybase.org/, respectively). For each amino acid type, duplicated sequences were removed and alignments of tRNA sequences were done using the TFAM package (Ardell and Andersson 2006). Only the COVEMF program was used: this program aligns a set of sequences to an existing alignment and takes into account both primary and secondary tRNA structures.…”

Initiator tRNA Genes Template the 3’CCA End at High Frequencies in Bacteria

“…We spotchecked several of these aberrant tRNA gene complements by examining their score distributions with TFAM 0.4 to verify that there were no viable candidates for initiator tRNA genes according to our models. All of the tRNA genes in these gene complements that we checked scored inside of the normal background distribution for the initiator tFAM model [10,12]. We believe that initiator tRNA genes may simply be missing from the genome annotations that were aggregated in tRNAdb-CE v.8.…”

“…However, currently available tRNA genefinders annotate all three classes as elongator tRNA Met genes [9]. The TFAM tRNA functional classifier, which uses profile-based models of whole tRNA sequences [10,11], can differentiate all three tRNA functional classes with generally high specificity and sensitivity (uniformly greater than 98% depending on data and models used) [12]. However, the tRNA Ile CAU class evolves more rapidly than other classes, so that even though the TFAM 1.4 proteobacterial-specific model generalizes well to some other bacterial phyla, this model does not generalize well to all [13].…”