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Genetics. 2012 Jul 30. [Epub ahead of print]
Clonal Interference in the Evolution of Influenza.
Strelkowa N, L?ssig M.
Source
Universit?t zu K?ln;
Abstract
The seasonal influenza A virus undergoes rapid evolution to escape human immune response. Adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral haemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the haemagglutinin coding sequence are observed about every 4 years. Here, we show that influenza A (H3N2) evolves by strong clonal interference. This mode of evolution is a red queen race between viral strains with different beneficial mutations. Clonal interference explains and quantifies the observed sweep pattern: We find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average. The inference of selection and clonal interference is based on frequency time-series of single-nucleotide polymorphisms, which are obtained from a sample of influenza genome sequences over 39 years. Our results imply that mode and speed of influenza evolution are governed not only by positive selection within, but also by background selection outside antigenic epitopes: immune adaptation and conservation of other viral functions interfere with each other. Hence, adapting viral proteins are predicted to be particularly brittle. We conclude that a quantitative understanding of influenza's evolutionary and epidemiological dynamics must be based on all genomic domains and functions coupled by clonal interference.
PMID:
22851649
[PubMed - as supplied by publisher]
Free full text
Clonal Interference in the Evolution of Influenza.
Strelkowa N, L?ssig M.
Source
Universit?t zu K?ln;
Abstract
The seasonal influenza A virus undergoes rapid evolution to escape human immune response. Adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral haemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the haemagglutinin coding sequence are observed about every 4 years. Here, we show that influenza A (H3N2) evolves by strong clonal interference. This mode of evolution is a red queen race between viral strains with different beneficial mutations. Clonal interference explains and quantifies the observed sweep pattern: We find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average. The inference of selection and clonal interference is based on frequency time-series of single-nucleotide polymorphisms, which are obtained from a sample of influenza genome sequences over 39 years. Our results imply that mode and speed of influenza evolution are governed not only by positive selection within, but also by background selection outside antigenic epitopes: immune adaptation and conservation of other viral functions interfere with each other. Hence, adapting viral proteins are predicted to be particularly brittle. We conclude that a quantitative understanding of influenza's evolutionary and epidemiological dynamics must be based on all genomic domains and functions coupled by clonal interference.
PMID:
22851649
[PubMed - as supplied by publisher]
Free full text
