Parallel evolution in the emergence of highly pathogenic avian influenza A viruses

Marina Escalera-Zamudio,Julien ThéZé,Jeremy Russell Keown,Bernardo GutiéRrez,Loic Carrique,Oliver G Pybus,Thomas A Bowden,Michael Golden,Bernardo Gutiérrez,Julien Thézé

doi:10.1038/s41467-020-19364-x

Marina Escalera-Zamudio, Julien ThéZé + Show 8 more

Open Access

https://doi.org/10.1038/s41467-020-19364-x

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Abstract

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here, we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs evolve independently from low-pathogenic ancestors via acquisition of polybasic cleavage sites. Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the viral genome. We combine phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein structure. Our resulting mutational panel may help to reveal new links between virulence evolution and other traits, and raises the possibility of predicting aspects of AIV evolution.

Highlights

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses
We further investigated if HAPMs that are significantly associated with the highly pathogenic (HP) phenotype are present in HP sequences that were not used in the subsampled alignments (Supplementary Data 3)
The occurrence of HAPMs in avian influenza viruses (AIV) genomes can be used as a starting point for the identification of circulating variants associated with the HP phenotype

Summary

Introduction

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. RNA viruses exhibit high rates of mutation (i.e. the rate at which errors are made during the virus genome replication), large population sizes, high replication rates, consistently varying environments, and strong selective pressures These factors, combined with small genome sizes, may restrict the number of mutational pathways that can lead to a given genotype, and may result in parallel molecular evolution being common in RNA viruses[16]. We hypothesise that the parallel evolution of the HP genotype from LP ancestors in AIV subtypes H5 and H7 may have a genetic basis, and may be associated with permissive or compensatory secondary mutations occurring elsewhere in the AIV genome Such mutations could arise prior to, or immediately after, the emergence of a pCS, perhaps to compensate for mutations with antagonistic pleiotropy, or which have detrimental effects on protein structure or folding stability[17,18]. Little is known about the genetic predisposition of AIV to acquire a pCS (except for the role of RNA structure at the cleavage site region itself19), nor about the role of mutations elsewhere in the virus genome that might favour the evolution of the HP phenotype

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