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In this work, we interrogate the International Pseudomonas Consortium Database (IPCD) to ask the question of whether CF-associated isolates display different patterns of evolutionary selection compared with environmental isolates. We do this by analysing dN\/dS for each open reading frame (ORF) in the CF-associated and environmental IPCD isolates. Most ORFs displayed a pronounced signature of negative selection (i.e. the ORFs were strongly conserved). However, 373 ORFs displayed non-negative selection, and of these, 206 manifested differential signatures of selection in the CF-derived and environmental isolates. Functional analysis of the ORFs under selection pressure in the CF airways revealed a statistically significant enrichment of enzymes catalysing reactions at metabolic branchpoints. More fine-grained analyses revealed niche-specific selection pressures in individual domains and protein surfaces. Finally, we show that gene loss in the psl biosynthetic gene cluster correlates with the presence of loss-of-function mutations in the mucoidy regulator, mucA. We speculate that elevated alginate production due to these mucA mutations compensates for the loss of Psl production in these isolates.<\/jats:p>","DOI":"10.1093\/narmme\/ugaf040","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:04:45Z","timestamp":1764248685000},"source":"Crossref","is-referenced-by-count":1,"title":["Genome-wide evolutionary selection pressures acting on\n                    <i>Pseudomonas aeruginosa<\/i>\n                    residing in different environments"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5565-1415","authenticated-orcid":false,"given":"Pok-Man","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Cambridge , Tennis Court Road, Cambridge , CB2 1QW,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahan Rudland","family":"Nazeer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge , Tennis Court Road, Cambridge , CB2 1QW,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3646-1733","authenticated-orcid":false,"given":"Martin","family":"Welch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge , Tennis Court Road, Cambridge , CB2 1QW,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"2025123107465725600_B1","doi-asserted-by":"publisher","first-page":"102328","DOI":"10.1016\/j.coi.2023.102328","article-title":"Microevolution of Pseudomonas aeruginosa in the airways of people with cystic fibrosis","volume":"83","author":"Cramer","year":"2023","journal-title":"Curr Opin 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