Universität zu Köln

Strelkowa, Natalja and Laessig, Michael (2012). Clonal Interference in the Evolution of Influenza. Genetics, 192 (2). S. 671 - 701. BETHESDA: GENETICS SOCIETY AMERICA. ISSN 1943-2631

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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 hemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the hemagglutinin 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Strelkowa, Natalja UNSPECIFIED UNSPECIFIED UNSPECIFIED Laessig, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482413
DOI:	10.1534/genetics.112.143396
Journal or Publication Title:	Genetics
Volume:	192
Number:	2
Page Range:	S. 671 - 701
Date:	2012
Publisher:	GENETICS SOCIETY AMERICA
Place of Publication:	BETHESDA
ISSN:	1943-2631
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ADAPTIVE PROTEIN EVOLUTION; BENEFICIAL MUTATIONS; POPULATION-DYNAMICS; A H3N2; ADAPTATION; SELECTION; FITNESS; MODEL; HEMAGGLUTININ; SUBSTITUTIONS Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48241