TY - JOUR

T1 - Evolutionary dynamics of bacteria in a human host environment

AU - Yang, Lei

AU - Jelsbak, Lars

AU - Marvig, Rasmus Lykke

AU - Damkiær, Søren

AU - Workman, Christopher

AU - Rau, Martin Holm

AU - Hansen, Susse Kirkelund

AU - Folkesson, Anders

AU - Johansen, Helle Krogh

AU - Ciofu, Oana

AU - Høiby, Niels

AU - Sommer, Morten

AU - Molin, Søren

PY - 2011/5/3

Y1 - 2011/5/3

N2 - 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.

AB - 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.

KW - Adaptation, Biological

KW - Base Sequence

KW - Biological Evolution

KW - Cystic Fibrosis

KW - DNA Primers

KW - Gene Expression Profiling

KW - Genetic Drift

KW - Genetic Pleiotropy

KW - Genetic Variation

KW - Genome, Bacterial

KW - Humans

KW - Molecular Sequence Data

KW - Oligonucleotide Array Sequence Analysis

KW - Phenotype

KW - Phylogeny

KW - Polymorphism, Single Nucleotide

KW - Pseudomonas aeruginosa

KW - Selection, Genetic

KW - Sequence Analysis, DNA

U2 - 10.1073/pnas.1018249108

DO - 10.1073/pnas.1018249108

M3 - Journal article

C2 - 21518885

VL - 108

SP - 7481

EP - 7486

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -