title: Comparative Analyses of Selection Operating on Nontranslated Intergenic Regions of Diverse Bacterial Species.
abstract: Nontranslated intergenic regions (IGRs) compose 10-15% of bacterial genomes, and contain many regulatory elements with key functions. Despite this, there are few systematic studies on the strength and direction of selection operating on IGRs in bacteria using whole-genome sequence data sets. Here we exploit representative whole-genome data sets from six diverse bacterial species:Staphylococcus aureus,Streptococcus pneumoniae,Mycobacterium tuberculosis,Salmonella enterica,Klebsiella pneumoniae, andEscherichia coliWe compare patterns of selection operating on IGRs using two independent methods: the proportion of singleton mutations and thedI/dSratio, wheredIis the number of intergenic SNPs per intergenic site. We find that the strength of purifying selection operating over all intergenic sites is consistently intermediate between that operating on synonymous and nonsynonymous sites. Ribosome binding sites and noncoding RNAs tend to be under stronger selective constraint than promoters and Rho-independent terminators. Strikingly, a clear signal of purifying selection remains even when all these major categories of regulatory elements are excluded, and this constraint is highest immediately upstream of genes. While a paucity of variation means that the data forM. tuberculosisare more equivocal than for the other species, we find strong evidence for positive selection within promoters of this species. This points to a key adaptive role for regulatory changes in this important pathogen. Our study underlines the feasibility and utility of gauging the selective forces operating on bacterial IGRs from whole-genome sequence data, and suggests that our current understanding of the functionality of these sequences is far from complete.
authors.affiliation: Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, BA2 7AY, United Kingdom.
authors.forename: Harry A
authors.identifier: 0000-0001-5895-3232
authors.initials: HA
authors.lastname: Thorpe
authors.affiliation: Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, BA2 7AY, United Kingdom.
authors.forename: Sion C
authors.identifier: 0000-0002-5997-2002
authors.initials: SC
authors.lastname: Bayliss
authors.affiliation: Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, BA2 7AY, United Kingdom.
authors.forename: Laurence D
authors.identifier: 0000-0001-6952-6797
authors.initials: LD
authors.lastname: Hurst
authors.affiliation: Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, BA2 7AY, United Kingdom e.feil@bath.ac.uk.
authors.forename: Edward J
authors.identifier: 0000-0003-1446-6744
authors.initials: EJ
authors.lastname: Feil
mesh_terms: D017124:Conserved Sequence / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D007711:Klebsiella pneumoniae / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000235:genetics; D019779:Salmonella enterica / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000235:genetics
chemical_list: D021901:DNA, Intergenic; D022661:RNA, Untranslated
keywords: bacterial genomics; intergenic regions (IGRs); purifying selection; whole-genome sequencing