title: Evolutionary dynamics of bacteria in a human host environment.
abstract: Laboratory evolution experiments have led to important findings relating organism adaptation and genomic evolution. However, continuous monitoring of long-term evolution has been lacking for natural systems, limiting our understanding of these processes in situ. Here we characterize the evolutionary dynamics of a lineage of a clinically important opportunistic bacterial pathogen, Pseudomonas aeruginosa, as it adapts to the airways of several individual cystic fibrosis patients over 200,000 bacterial generations, and provide estimates of mutation rates of bacteria in a natural environment. In contrast to predictions based on in vitro evolution experiments, we document limited diversification of the evolving lineage despite a highly structured and complex host environment. Notably, the lineage went through an initial period of rapid adaptation caused by a small number of mutations with pleiotropic effects, followed by a period of genetic drift with limited phenotypic change and a genomic signature of negative selection, suggesting that the evolving lineage has reached a major adaptive peak in the fitness landscape. This contrasts with previous findings of continued positive selection from long-term in vitro evolution experiments. The evolved phenotype of the infecting bacteria further suggests that the opportunistic pathogen has transitioned to become a primary pathogen for cystic fibrosis patients.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Lars
authors.initials: L
authors.lastname: Jelsbak
authors.forename: Rasmus Lykke
authors.initials: RL
authors.lastname: Marvig
authors.forename: Søren
authors.initials: S
authors.lastname: Damkiær
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.forename: Martin Holm
authors.initials: MH
authors.lastname: Rau
authors.forename: Susse Kirkelund
authors.initials: SK
authors.lastname: Hansen
authors.forename: Anders
authors.initials: A
authors.lastname: Folkesson
authors.forename: Helle Krogh
authors.initials: HK
authors.lastname: Johansen
authors.forename: Oana
authors.initials: O
authors.lastname: Ciofu
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.forename: Morten O A
authors.initials: MO
authors.lastname: Sommer
authors.forename: Søren
authors.initials: S
authors.lastname: Molin
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D003550:Cystic Fibrosis / Q000382:microbiology*; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D040961:Genetic Drift; D058685:Genetic Pleiotropy / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers