Translational selection is ubiquitous in prokaryotes

• Published in: PLoS genetics Vol. 6; no. 6; p. e1001004
• Main Authors: Supek, Fran, Skunca, Nives, Repar, Jelena, Vlahovicek, Kristian, Smuc, Tomislav
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-05-2010; Public Library of Science (PLoS)
• Subjects: Archaea; Archaea - genetics; Bacteria; Bacteria - genetics; Bias; Biochemistry/Molecular Evolution; Biochemistry/Transcription and Translation; Cell Biology/Microbial Physiology and Metabolism; Codon; Computational Biology/Genomics; Computational Biology/Systems Biology; Computer Science/Applications; DNA; Ecology/Environmental Microbiology; Escherichia coli; Evolutionary Biology/Microbial Evolution and Genomics; Gene Expression Regulation; Genes; Genetic aspects; Genetic translation; Genetics; Genetics and Genomics/Comparative Genomics; Genetics and Genomics/Functional Genomics; Genetics and Genomics/Gene Expression; Genome; Genomes; Intergenic DNA; Microbiology; Models, Genetic; Ontology; Physiological aspects; Preferences; Prokaryotes; Prokaryotic Cells - metabolism; Protein Biosynthesis; Proteins; Ribosomal Proteins - genetics; Norway; Croatia
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1001004

Codon usage bias in prokaryotic genomes is largely a consequence of background substitution patterns in DNA, but highly expressed genes may show a preference towards codons that enable more efficient and/or accurate translation. We introduce a novel approach based on supervised machine learning that detects effects of translational selection on genes, while controlling for local variation in nucleotide substitution patterns represented as sequence composition of intergenic DNA. A cornerstone of our method is a Random Forest classifier that outperformed previous distance measure-based approaches, such as the codon adaptation index, in the task of discerning the (highly expressed) ribosomal protein genes by their codon frequencies. Unlike previous reports, we show evidence that translational selection in prokaryotes is practically universal: in 460 of 461 examined microbial genomes, we find that a subset of genes shows a higher codon usage similarity to the ribosomal proteins than would be expected from the local sequence composition. These genes constitute a substantial part of the genome--between 5% and 33%, depending on genome size--while also exhibiting higher experimentally measured mRNA abundances and tending toward codons that match tRNA anticodons by canonical base pairing. Certain gene functional categories are generally enriched with, or depleted of codon-optimized genes, the trends of enrichment/depletion being conserved between Archaea and Bacteria. Prominent exceptions from these trends might indicate genes with alternative physiological roles; we speculate on specific examples related to detoxication of oxygen radicals and ammonia and to possible misannotations of asparaginyl-tRNA synthetases. Since the presence of codon optimizations on genes is a valid proxy for expression levels in fully sequenced genomes, we provide an example of an "adaptome" by highlighting gene functions with expression levels elevated specifically in thermophilic Bacteria and Archaea.