Frequent gain and loss of functional transcription factor binding sites.
Cis-regulatory sequences are not always conserved across species. Divergence within cis-regulatory sequences may result from the evolution of species-specific patterns of gene expression or the flexible nature of the cis-regulatory code. The identification of functional divergence in cis-regulatory...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-05-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC1876492?pdf=render |
| _version_ | 1829137715784843264 |
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| author | Scott W Doniger Justin C Fay |
| author_facet | Scott W Doniger Justin C Fay |
| author_sort | Scott W Doniger |
| collection | DOAJ |
| description | Cis-regulatory sequences are not always conserved across species. Divergence within cis-regulatory sequences may result from the evolution of species-specific patterns of gene expression or the flexible nature of the cis-regulatory code. The identification of functional divergence in cis-regulatory sequences is therefore important for both understanding the role of gene regulation in evolution and annotating regulatory elements. We have developed an evolutionary model to detect the loss of constraint on individual transcription factor binding sites (TFBSs). We find that a significant fraction of functionally constrained binding sites have been lost in a lineage-specific manner among three closely related yeast species. Binding site loss has previously been explained by turnover, where the concurrent gain and loss of a binding site maintains gene regulation. We estimate that nearly half of all loss events cannot be explained by binding site turnover. Recreating the mutations that led to binding site loss confirms that these sequence changes affect gene expression in some cases. We also estimate that there is a high rate of binding site gain, as more than half of experimentally identified S. cerevisiae binding sites are not conserved across species. The frequent gain and loss of TFBSs implies that cis-regulatory sequences are labile and, in the absence of turnover, may contribute to species-specific patterns of gene expression. |
| first_indexed | 2024-12-14T19:03:06Z |
| format | Article |
| id | doaj.art-a379c382f65140adabb6397a4e90e556 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-14T19:03:06Z |
| publishDate | 2007-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-a379c382f65140adabb6397a4e90e5562022-12-21T22:50:54ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582007-05-0135e9910.1371/journal.pcbi.0030099Frequent gain and loss of functional transcription factor binding sites.Scott W DonigerJustin C FayCis-regulatory sequences are not always conserved across species. Divergence within cis-regulatory sequences may result from the evolution of species-specific patterns of gene expression or the flexible nature of the cis-regulatory code. The identification of functional divergence in cis-regulatory sequences is therefore important for both understanding the role of gene regulation in evolution and annotating regulatory elements. We have developed an evolutionary model to detect the loss of constraint on individual transcription factor binding sites (TFBSs). We find that a significant fraction of functionally constrained binding sites have been lost in a lineage-specific manner among three closely related yeast species. Binding site loss has previously been explained by turnover, where the concurrent gain and loss of a binding site maintains gene regulation. We estimate that nearly half of all loss events cannot be explained by binding site turnover. Recreating the mutations that led to binding site loss confirms that these sequence changes affect gene expression in some cases. We also estimate that there is a high rate of binding site gain, as more than half of experimentally identified S. cerevisiae binding sites are not conserved across species. The frequent gain and loss of TFBSs implies that cis-regulatory sequences are labile and, in the absence of turnover, may contribute to species-specific patterns of gene expression.http://europepmc.org/articles/PMC1876492?pdf=render |
| spellingShingle | Scott W Doniger Justin C Fay Frequent gain and loss of functional transcription factor binding sites. PLoS Computational Biology |
| title | Frequent gain and loss of functional transcription factor binding sites. |
| title_full | Frequent gain and loss of functional transcription factor binding sites. |
| title_fullStr | Frequent gain and loss of functional transcription factor binding sites. |
| title_full_unstemmed | Frequent gain and loss of functional transcription factor binding sites. |
| title_short | Frequent gain and loss of functional transcription factor binding sites. |
| title_sort | frequent gain and loss of functional transcription factor binding sites |
| url | http://europepmc.org/articles/PMC1876492?pdf=render |
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