title: Error compensation of tRNA misacylation by codon-anticodon mismatch prevents translational amino acid misinsertion.
abstract: Codon-anticodon mismatches and tRNA misloadings cause translational amino acid misinsertions, producing dysfunctional proteins. Here I explore the original hypothesis whether mismatches tend to compensate misacylation, so as to insert the amino acid coded by the codon. This error compensation is promoted by the fact that codon-anticodon mismatch stabilities increase with tRNA misacylation potentials (predicted by 'tfam') by non-cognate amino acids coded by the mismatched codons for most tRNAs examined. Error compensation is independent of preferential misacylation by non-cognate amino acids physico-chemically similar to cognate amino acids, a phenomenon that decreases misinsertion impacts. Error compensation correlates negatively with (a) codon/anticodon abundance (in human mitochondria and Escherichia coli); (b) developmental instability (estimated by fluctuating asymmetry in bilateral counts of subdigital lamellae, in each of two lizard genera, Anolis and Sceloporus); and (c) pathogenicity of human mitochondrial tRNA polymorphisms. Patterns described here suggest that tRNA misacylation is sometimes compensated by codon-anticodon mismatches. Hence translation inserts the amino acid coded by the mismatched codon, despite mismatch and misloading. Results suggest that this phenomenon is sufficiently important to affect whole organism phenotypes, as shown by correlations with pathologies and morphological estimates of developmental stability.
authors.affiliation: Department of Evolution, Ecology & Behavior, The Hebrew University of Jerusalem, Israel. herves@bio.uio.no
authors.forename: Hervé
authors.initials: H
authors.lastname: Seligmann
mesh_terms: D000215:Acylation; D000818:Animals; D000926:Anticodon / Q000235:genetics*; D020137:Base Pair Mismatch; D003062:Codon / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic; D012323:RNA Processing, Post-Transcriptional; D012343:RNA, Transfer / Q000378:metabolism*
chemical_list: D000926:Anticodon; D003062:Codon; D012343:RNA, Transfer