Stability-mediated epistasis constrains the evolution of an influenza protein
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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/00631 |
| _version_ | 1828382897710563328 |
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| author | Lizhi Ian Gong Marc A Suchard Jesse D Bloom |
| author_facet | Lizhi Ian Gong Marc A Suchard Jesse D Bloom |
| author_sort | Lizhi Ian Gong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T04:39:17Z |
| format | Article |
| id | doaj.art-0fe644f1302b4ee1b3de180f910a0c83 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:39:17Z |
| publishDate | 2013-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0fe644f1302b4ee1b3de180f910a0c832022-12-22T02:01:55ZengeLife Sciences Publications LtdeLife2050-084X2013-05-01210.7554/eLife.00631Stability-mediated epistasis constrains the evolution of an influenza proteinLizhi Ian Gong0Marc A Suchard1Jesse D Bloom2Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartments of Biomathematics, Biostatistics, and Human Genetics, University of California, Los Angeles, Los Angeles, United StatesDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States; Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, United StatesJohn 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.https://elifesciences.org/articles/00631epistasisprotein evolutioninfluenzaprotein stability |
| spellingShingle | Lizhi Ian Gong Marc A Suchard Jesse D Bloom Stability-mediated epistasis constrains the evolution of an influenza protein eLife epistasis protein evolution influenza protein stability |
| title | Stability-mediated epistasis constrains the evolution of an influenza protein |
| title_full | Stability-mediated epistasis constrains the evolution of an influenza protein |
| title_fullStr | Stability-mediated epistasis constrains the evolution of an influenza protein |
| title_full_unstemmed | Stability-mediated epistasis constrains the evolution of an influenza protein |
| title_short | Stability-mediated epistasis constrains the evolution of an influenza protein |
| title_sort | stability mediated epistasis constrains the evolution of an influenza protein |
| topic | epistasis protein evolution influenza protein stability |
| url | https://elifesciences.org/articles/00631 |
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