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Coordinated Evolution of Influenza A Surface Proteins


The fitness of an organism depends on the coordinated function of many genes. Thus, how a mutation in one gene affects fitness often depends on what mutations are present in other genes. This dependence is called “genetic interaction” or “epistasis”. The prevalence and type of such interactions are not well understood. Epistasis can be inferred from time-series sequencing data when a mutation in one gene is observed to facilitate the spread of a mutation in another gene. However, the situation is much more complicated when new combinations of genes are formed by processes such as recombination or reassortment. In such cases, deducing the time and order of genetic changes is difficult. Here, we devise a method to infer pairs of mutations in different genes which closely follow one another in the presence of reassortment. We apply it to evolution of two surface proteins of influenza A virus, hemagglutinin and neuraminidase, which are important targets for the human immune system and drugs. We show that mutations in one of these proteins are often facilitated by prior mutations, or compensated by subsequent mutations, in the other protein. In particular, drug-resistance mutations in neuraminidase were likely made possible by prior mutation in hemagglutinin. Knowledge of such interactions is necessary to fully understand and predict evolution.


Vyšlo v časopise: Coordinated Evolution of Influenza A Surface Proteins. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005404
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005404

Souhrn

The fitness of an organism depends on the coordinated function of many genes. Thus, how a mutation in one gene affects fitness often depends on what mutations are present in other genes. This dependence is called “genetic interaction” or “epistasis”. The prevalence and type of such interactions are not well understood. Epistasis can be inferred from time-series sequencing data when a mutation in one gene is observed to facilitate the spread of a mutation in another gene. However, the situation is much more complicated when new combinations of genes are formed by processes such as recombination or reassortment. In such cases, deducing the time and order of genetic changes is difficult. Here, we devise a method to infer pairs of mutations in different genes which closely follow one another in the presence of reassortment. We apply it to evolution of two surface proteins of influenza A virus, hemagglutinin and neuraminidase, which are important targets for the human immune system and drugs. We show that mutations in one of these proteins are often facilitated by prior mutations, or compensated by subsequent mutations, in the other protein. In particular, drug-resistance mutations in neuraminidase were likely made possible by prior mutation in hemagglutinin. Knowledge of such interactions is necessary to fully understand and predict evolution.


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