{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:27:30Z","timestamp":1792146450635,"version":"4.4.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"30","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,7,28]]},"abstract":"<jats:p>\n                    Core genes comprising the ubiquitous backbone of bacterial genomes are not subject to frequent horizontal transfer and generally are not thought to contribute to the adaptive evolution of bacterial pathogens. We determined, however, that at least one-third and possibly more than one-half of the core genes in\n                    <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n                    genomes are targeted by repeated replacement substitutions in the same amino acid positions\u2014hotspot mutations. Occurrence of hotspot mutations is driven by positive selection, as their rate is significantly higher than expected by random chance alone, and neither intragenic recombination nor increased mutability can explain the observed patterns. Also, commensal\n                    <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n                    strains have a significantly lower frequency of mutated genes and mutations per genome than pathogenic strains.\n                    <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n                    strains causing extra-intestinal infections accumulate hotspot mutations at the highest rate, whereas the highest total number of mutated genes has been found among\n                    <jats:italic>Shigella<\/jats:italic>\n                    isolates, suggesting the pathoadaptive nature of such mutations. The vast majority of hotspot mutations are of recent evolutionary origin, implying short-term positive selection, where adaptive mutations emerge repeatedly but are not sustained in natural circulation for long. Such pattern of dynamics is consistent with source-sink model of virulence evolution.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0906217106","type":"journal-article","created":{"date-parts":[[2009,7,15]],"date-time":"2009-07-15T21:45:58Z","timestamp":1247694358000},"page":"12412-12417","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":99,"title":["High frequency of hotspot mutations in core genes of Escherichia coli due to short-term positive selection"],"prefix":"10.1073","volume":"106","author":[{"given":"Sujay","family":"Chattopadhyay","sequence":"first","affiliation":[{"name":"Department of Microbiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Weissman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir N.","family":"Minin","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Washington, Seattle, WA 98195;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Russo","sequence":"additional","affiliation":[{"name":"Veterans Administration Western New York Healthcare System,"},{"name":"Department of Medicine, and"},{"name":"Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Dykhuizen","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolution, University at Stony Brook, State University of New York, Stony Brook, NY 11794"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeni V.","family":"Sokurenko","sequence":"additional","affiliation":[{"name":"Department of Microbiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,7,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-4539-z"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04239"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-007-0200-z"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507415102"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro884"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(99)01493-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.130000"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00619-08"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252529799"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603038103"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01744-06"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600938103"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6254707"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/123.3.585"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/133.3.693"},{"key":"e_1_3_3_16_2","first-page":"418","article-title":"Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions","volume":"3","author":"Nei M","year":"1986","unstructured":"M Nei, T Gojobori, Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. 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