Components of selection in the evolution of the influenza virus: linkage effects beat inherent selection

Andino, R., Illingworth, C. J.R. and Mustonen, V. (2012) Components of selection in the evolution of the influenza virus: linkage effects beat inherent selection. PLoS Pathogens, 8(12), e1003091. (doi: 10.1371/journal.ppat.1003091) (PMID:23300444) (PMCID:PMC3531508)

Abstract

The influenza virus is an important human pathogen, with a rapid rate of evolution in the human population. The rate of homologous recombination within genes of influenza is essentially zero. As such, where two alleles within the same gene are in linkage disequilibrium, interference between alleles will occur, whereby selection acting upon one allele has an influence upon the frequency of the other. We here measured the relative importance of selection and interference effects upon the evolution of influenza. We considered time-resolved allele frequency data from the global evolutionary history of the haemagglutinin gene of human influenza A/H3N2, conducting an in-depth analysis of sequences collected since 1996. Using a model that accounts for selection-caused interference between alleles in linkage disequilibrium, we estimated the inherent selective benefit of individual polymorphisms in the viral population. These inherent selection coefficients were in turn used to calculate the total selective effect of interference acting upon each polymorphism, considering the effect of the initial background upon which a mutation arose, and the subsequent effect of interference from other alleles that were under selection. Viewing events in retrospect, we estimated the influence of each of these components in determining whether a mutant allele eventually fixed or died in the global viral population. Our inherent selection coefficients, when combined across different regions of the protein, were consistent with previous measurements of dN/dS for the same system. Alleles going on to fix in the global population tended to be under more positive selection, to arise on more beneficial backgrounds, and to avoid strong negative interference from other alleles under selection. However, on average, the fate of a polymorphism was determined more by the combined influence of interference effects than by its inherent selection coefficient.

• Item Type: Articles
• Additional Information: This work was supported by the Wellcome Trust under grant reference 098051. This research was supported in part by the National Science Foundation under Grant No. NSF PHY05-51164 during a visit at the Kavli Institute of Theoretical Physics (KITP, Santa Barbara, CA).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Andino, R., Illingworth, C. J.R., and Mustonen, V.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in PLoS Pathogens 8(12):e1003091
• Publisher Policy: Reproduced under a Creative Commons License