Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites
Complexes of specifically interacting molecules, such as transcription factor proteins (TFs) and the DNA response elements (REs) they recognize, control most biological processes, but little is known concerning the functional and evolutionary effects of epistatic interactions across molecular interf...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/07864 |
| _version_ | 1811236806055690240 |
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| author | Dave W Anderson Alesia N McKeown Joseph W Thornton |
| author_facet | Dave W Anderson Alesia N McKeown Joseph W Thornton |
| author_sort | Dave W Anderson |
| collection | DOAJ |
| description | Complexes of specifically interacting molecules, such as transcription factor proteins (TFs) and the DNA response elements (REs) they recognize, control most biological processes, but little is known concerning the functional and evolutionary effects of epistatic interactions across molecular interfaces. We experimentally characterized all combinations of genotypes in the joint protein-DNA sequence space defined by an historical transition in TF-RE specificity that occurred some 500 million years ago in the DNA-binding domain of an ancient steroid hormone receptor. We found that rampant epistasis within and between the two molecules was essential to specific TF-RE recognition and to the evolution of a novel TF-RE complex with unique derived specificity. Permissive and restrictive epistatic mutations across the TF-RE interface opened and closed potential evolutionary paths accessible by the other, making the evolution of each molecule contingent on its partner's history and allowing a molecular complex with novel specificity to evolve. |
| first_indexed | 2024-04-12T12:14:25Z |
| format | Article |
| id | doaj.art-5189ae9b95f047f5a8cd1a86ea03eebf |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:14:25Z |
| publishDate | 2015-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5189ae9b95f047f5a8cd1a86ea03eebf2022-12-22T03:33:28ZengeLife Sciences Publications LtdeLife2050-084X2015-06-01410.7554/eLife.07864Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sitesDave W Anderson0Alesia N McKeown1Joseph W Thornton2Institute of Ecology and Evolution, University of Oregon, Eugene, United StatesInstitute of Ecology and Evolution, University of Oregon, Eugene, United StatesDepartment of Ecology and Evolution, University of Chicago, Chicago, United States; Department of Human Genetics, University of Chicago, Chicago, United StatesComplexes of specifically interacting molecules, such as transcription factor proteins (TFs) and the DNA response elements (REs) they recognize, control most biological processes, but little is known concerning the functional and evolutionary effects of epistatic interactions across molecular interfaces. We experimentally characterized all combinations of genotypes in the joint protein-DNA sequence space defined by an historical transition in TF-RE specificity that occurred some 500 million years ago in the DNA-binding domain of an ancient steroid hormone receptor. We found that rampant epistasis within and between the two molecules was essential to specific TF-RE recognition and to the evolution of a novel TF-RE complex with unique derived specificity. Permissive and restrictive epistatic mutations across the TF-RE interface opened and closed potential evolutionary paths accessible by the other, making the evolution of each molecule contingent on its partner's history and allowing a molecular complex with novel specificity to evolve.https://elifesciences.org/articles/07864evolutionbiochemistryepistasissequence spacetranscription factorpermissive mutation |
| spellingShingle | Dave W Anderson Alesia N McKeown Joseph W Thornton Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites eLife evolution biochemistry epistasis sequence space transcription factor permissive mutation |
| title | Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites |
| title_full | Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites |
| title_fullStr | Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites |
| title_full_unstemmed | Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites |
| title_short | Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites |
| title_sort | intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its dna binding sites |
| topic | evolution biochemistry epistasis sequence space transcription factor permissive mutation |
| url | https://elifesciences.org/articles/07864 |
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