An incoherent feedforward loop facilitates adaptive tuning of gene expression
We studied adaptive evolution of gene expression using long-term experimental evolution of Saccharomyces cerevisiae in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32323 |
| _version_ | 1828375856369631232 |
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| author | Jungeui Hong Nathan Brandt Farah Abdul-Rahman Ally Yang Tim Hughes David Gresham |
| author_facet | Jungeui Hong Nathan Brandt Farah Abdul-Rahman Ally Yang Tim Hughes David Gresham |
| author_sort | Jungeui Hong |
| collection | DOAJ |
| description | We studied adaptive evolution of gene expression using long-term experimental evolution of Saccharomyces cerevisiae in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repressor, DAL80 in an incoherent type-1 feedforward loop (I1-FFL) to control expression of the high affinity ammonium transporter gene, MEP2. Missense mutations in the DNA binding domain of GAT1 reduce its binding to the GATAA consensus sequence. However, we show experimentally, and using mathematical modeling, that decreases in GAT1 binding result in increased expression of MEP2 as a consequence of properties of I1-FFLs. Our results show that I1-FFLs, one of the most commonly occurring network motifs in transcriptional networks, can facilitate adaptive tuning of gene expression through modulation of transcription factor binding affinities. Our findings highlight the importance of gene regulatory architectures in the evolution of gene expression. |
| first_indexed | 2024-04-14T07:52:49Z |
| format | Article |
| id | doaj.art-70b162886c734dc89f37eaa37fc40ab4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:52:49Z |
| publishDate | 2018-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-70b162886c734dc89f37eaa37fc40ab42022-12-22T02:05:09ZengeLife Sciences Publications LtdeLife2050-084X2018-04-01710.7554/eLife.32323An incoherent feedforward loop facilitates adaptive tuning of gene expressionJungeui Hong0Nathan Brandt1Farah Abdul-Rahman2Ally Yang3Tim Hughes4David Gresham5https://orcid.org/0000-0002-4028-0364Department of Biology, Center for Genomics and Systems Biology, New York University, New York, United States; Memorial Sloan Kettering Cancer Center, New York, United StatesDepartment of Biology, Center for Genomics and Systems Biology, New York University, New York, United StatesDepartment of Biology, Center for Genomics and Systems Biology, New York University, New York, United StatesBanting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, CanadaBanting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, CanadaDepartment of Biology, Center for Genomics and Systems Biology, New York University, New York, United StatesWe studied adaptive evolution of gene expression using long-term experimental evolution of Saccharomyces cerevisiae in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repressor, DAL80 in an incoherent type-1 feedforward loop (I1-FFL) to control expression of the high affinity ammonium transporter gene, MEP2. Missense mutations in the DNA binding domain of GAT1 reduce its binding to the GATAA consensus sequence. However, we show experimentally, and using mathematical modeling, that decreases in GAT1 binding result in increased expression of MEP2 as a consequence of properties of I1-FFLs. Our results show that I1-FFLs, one of the most commonly occurring network motifs in transcriptional networks, can facilitate adaptive tuning of gene expression through modulation of transcription factor binding affinities. Our findings highlight the importance of gene regulatory architectures in the evolution of gene expression.https://elifesciences.org/articles/32323transcription factorsexperimental evolutiongene expression |
| spellingShingle | Jungeui Hong Nathan Brandt Farah Abdul-Rahman Ally Yang Tim Hughes David Gresham An incoherent feedforward loop facilitates adaptive tuning of gene expression eLife transcription factors experimental evolution gene expression |
| title | An incoherent feedforward loop facilitates adaptive tuning of gene expression |
| title_full | An incoherent feedforward loop facilitates adaptive tuning of gene expression |
| title_fullStr | An incoherent feedforward loop facilitates adaptive tuning of gene expression |
| title_full_unstemmed | An incoherent feedforward loop facilitates adaptive tuning of gene expression |
| title_short | An incoherent feedforward loop facilitates adaptive tuning of gene expression |
| title_sort | incoherent feedforward loop facilitates adaptive tuning of gene expression |
| topic | transcription factors experimental evolution gene expression |
| url | https://elifesciences.org/articles/32323 |
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