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Open Access Highly Accessed Research article

Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

Emily HM Wong1, David K Smith2*, Raul Rabadan3, Malik Peiris1 and Leo LM Poon1*

Author Affiliations

1 Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, China

2 Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China

3 Department of Biomedical Informatics and Center for Computational Biology and Bioinformatics, Columbia University College of Physicians and Surgeons, New York, USA

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BMC Evolutionary Biology 2010, 10:253  doi:10.1186/1471-2148-10-253

Published: 19 August 2010

Abstract

Background

The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.

Results

Relative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus.

Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.

Conclusions

Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.