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Stability-mediated epistasis constrains the evolution of an influenza protein

Open access
Gong, Lizhi Ian, Suchard, Marc A, Bloom, Jesse D·2013·eLife

Abstract

John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value.

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Metadata

Authors
Gong, L. I., Suchard, M. A., & Bloom, J. D.
Venue
eLife
Published
2013-05-14
Volume
2
Pages
e00631-e00631
ISSN
2050-084X (ISSN-L)
OpenAlex
W2113557726
Cited by
336
References
6
FWCI
19.02
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Stability-mediated epistasis constrains the evolution of an influenza protein. https://app.cochat.ai/papers/10.7554/elife.00631
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Gong, L. I., Suchard, M. A., & Bloom, J. D. (2013). Stability-mediated epistasis constrains the evolution of an influenza protein. eLife. https://doi.org/10.7554/elife.00631

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