Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus

Proceedings of the National Academy of Sciences of the United States of America - Tập 100 Số 12 - Trang 7152-7157 - 2003
Joshua B. Plotkin1, Jonathan Dushoff1
1Institute for Advanced Study, Olden Lane, Princeton, NJ 08540; and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08540

Tóm tắt

Although the surface proteins of human influenza A virus evolve rapidly and continually produce antigenic variants, the internal viral genes acquire mutations very gradually. In this paper, we analyze the sequence evolution of three influenza A genes over the past two decades. We study codon usage as a discriminating signature of gene- and even residue-specific diversifying and purifying selection. Nonrandom codon choice can increase or decrease the effective local substitution rate. We demonstrate that the codons of hemagglutinin, particularly those in the antibody-combining regions, are significantly biased toward substitutional point mutations relative to the codons of other influenza virus genes. We discuss the evolutionary interpretation and implications of these biases for hemagglutinin's antigenic evolution. We also introduce information-theoretic methods that use sequence data to detect regions of recent positive selection and potential protein conformational changes.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 100 Số 12

7152-7157

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