Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution
Abstract Enzyme evolution is characterized by constant alterations of the intramolecular residue networks supporting their functions. The rewiring of these network interactions can give rise to epistasis. As mutations accumulate, the epistasis observed across diverse genotypes may appear idiosyncrat...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44333-5 |
| _version_ | 1797376946047287296 |
|---|---|
| author | Karol Buda Charlotte M. Miton Nobuhiko Tokuriki |
| author_facet | Karol Buda Charlotte M. Miton Nobuhiko Tokuriki |
| author_sort | Karol Buda |
| collection | DOAJ |
| description | Abstract Enzyme evolution is characterized by constant alterations of the intramolecular residue networks supporting their functions. The rewiring of these network interactions can give rise to epistasis. As mutations accumulate, the epistasis observed across diverse genotypes may appear idiosyncratic, that is, exhibit unique effects in different genetic backgrounds. Here, we unveil a quantitative picture of the prevalence and patterns of epistasis in enzyme evolution by analyzing 41 fitness landscapes generated from seven enzymes. We show that >94% of all mutational and epistatic effects appear highly idiosyncratic, which greatly distorted the functional prediction of the evolved enzymes. By examining seemingly idiosyncratic changes in epistasis along adaptive trajectories, we expose several instances of higher-order, intramolecular rewiring. Using complementary structural data, we outline putative molecular mechanisms explaining higher-order epistasis along two enzyme trajectories. Our work emphasizes the prevalence of epistasis and provides an approach to exploring this phenomenon through a molecular lens. |
| first_indexed | 2024-03-08T19:45:55Z |
| format | Article |
| id | doaj.art-ed9c301639f8490585260f0c6db1f941 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T19:45:55Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-ed9c301639f8490585260f0c6db1f9412023-12-24T12:24:20ZengNature PortfolioNature Communications2041-17232023-12-0114111210.1038/s41467-023-44333-5Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolutionKarol Buda0Charlotte M. Miton1Nobuhiko Tokuriki2Michael Smith Laboratories, University of British ColumbiaMichael Smith Laboratories, University of British ColumbiaMichael Smith Laboratories, University of British ColumbiaAbstract Enzyme evolution is characterized by constant alterations of the intramolecular residue networks supporting their functions. The rewiring of these network interactions can give rise to epistasis. As mutations accumulate, the epistasis observed across diverse genotypes may appear idiosyncratic, that is, exhibit unique effects in different genetic backgrounds. Here, we unveil a quantitative picture of the prevalence and patterns of epistasis in enzyme evolution by analyzing 41 fitness landscapes generated from seven enzymes. We show that >94% of all mutational and epistatic effects appear highly idiosyncratic, which greatly distorted the functional prediction of the evolved enzymes. By examining seemingly idiosyncratic changes in epistasis along adaptive trajectories, we expose several instances of higher-order, intramolecular rewiring. Using complementary structural data, we outline putative molecular mechanisms explaining higher-order epistasis along two enzyme trajectories. Our work emphasizes the prevalence of epistasis and provides an approach to exploring this phenomenon through a molecular lens.https://doi.org/10.1038/s41467-023-44333-5 |
| spellingShingle | Karol Buda Charlotte M. Miton Nobuhiko Tokuriki Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution Nature Communications |
| title | Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution |
| title_full | Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution |
| title_fullStr | Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution |
| title_full_unstemmed | Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution |
| title_short | Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution |
| title_sort | pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution |
| url | https://doi.org/10.1038/s41467-023-44333-5 |
| work_keys_str_mv | AT karolbuda pervasiveepistasisexposesintramolecularnetworksinadaptiveenzymeevolution AT charlottemmiton pervasiveepistasisexposesintramolecularnetworksinadaptiveenzymeevolution AT nobuhikotokuriki pervasiveepistasisexposesintramolecularnetworksinadaptiveenzymeevolution |