title: Refined analyses suggest that recombination is a minor source of genomic diversity inPseudomonas aeruginosachronic cystic fibrosis infections.
abstract: Chronic bacterial airway infections in people with cystic fibrosis (CF) are often caused byPseudomonas aeruginosa, typically showing high phenotypic diversity amongst co-isolates from the same sputum sample. Whilst adaptive evolution during chronic infections has been reported, the genetic mechanisms underlying the observed rapid within-population diversification are not well understood. Two recent conflicting reports described very high and low rates of homologous recombination in two closely relatedP. aeruginosapopulations from the lungs of different chronically infected CF patients. To investigate the underlying cause of these contrasting observations, we combined the short read datasets from both studies and applied a new comparative analysis. We inferred low rates of recombination in both populations. The discrepancy in the findings of the two previous studies can be explained by differences in the application of variant calling techniques. Two novel algorithms were developed that filter false-positive variants. The first algorithm filters variants on the basis of ambiguity within duplications in the reference genome. The second omits probable false-positive variants at regions of non-homology between reference and sample caused by structural rearrangements. As gains and losses of prophage or genomic islands are frequent causes of chromosomal rearrangements within microbial populations, this filter has broad appeal for mitigating false-positive variant calls. Both algorithms are available in a Python package.
authors.affiliation: 1​Institute of Integrative Biology, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.affiliation: 1​Institute of Integrative Biology, Biosciences Building, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Paterson
authors.affiliation: 2​Department of Biology, University of York, Wentworth Way, York YO10 5DD, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brockhurst
authors.affiliation: 3​Clinical Infection, Microbiology & Immunology, Institute of Infection & Global Health, University of Liverpool, 8 West Derby Street, Liverpool L69 7BE, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Winstanley
mesh_terms: D000465:Algorithms; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications*; D014644:Genetic Variation / Q000235:genetics; D023281:Genomics; D006801:Humans; D011552:Pseudomonas Infections / Q000209:etiology* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*
keywords: BAGA; Pseudomonas aeruginosa; cystic fibrosis; genomic diversity; recombination