Position specific variation in the rate of evolution in transcription factor binding sites
Background: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Software |
| Language: | English |
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BioMed Central Ltd
2010
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| Online Access: | http://hdl.handle.net/1721.1/59308 |
| _version_ | 1826199902709874688 |
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| author | Kellis, Manolis Moses, Alan M. Chiang, Derek Y. Eisen, Michael B. Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kellis, Manolis Moses, Alan M. Chiang, Derek Y. Eisen, Michael B. Lander, Eric Steven |
| author_sort | Kellis, Manolis |
| collection | MIT |
| description | Background: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Results: Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. Conclusion: As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA. |
| first_indexed | 2024-09-23T11:27:38Z |
| format | Software |
| id | mit-1721.1/59308 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:27:38Z |
| publishDate | 2010 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/593082022-09-27T19:40:42Z Position specific variation in the rate of evolution in transcription factor binding sites Kellis, Manolis Moses, Alan M. Chiang, Derek Y. Eisen, Michael B. Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Laboratory for Computer Science Kellis, Manolis Lander, Eric S. Artifacts Base composition Base sequence Binding sites, genetics Computational biology, methods Computational biology, statistics & numerical data Conserved sequence Evolution, molecular Gene expression regulation, fungal Genetic variation Genome, fungal Mutagenesis Predictive value of tests Promoter regions, genetic Promoter regions, genetic, physiology Saccharomyces, genetics Saccharomyces cerevisiae, genetics Transcription factors, genetics Transcription factors, metabolism Transcription, genetic Background: The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Results: Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. Conclusion: As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the effective use of comparative sequence data in the identification of transcription factor binding sites and is an important step toward understanding the evolution of functional non-coding DNA. United States. Dept. of Energy (contract no. ED-AC03-76SF00098) 2010-10-14T12:33:24Z 2010-10-14T12:33:24Z 2003-08 2003-05 2010-09-03T16:06:53Z Software http://purl.org/eprint/type/JournalArticle 1471-2148 http://hdl.handle.net/1721.1/59308 Moses, Alan M., Derek Y. Chiang, Manolis Kellis, Eric S. Lander, and Michael B. Eisen (2003). Position specific variation in the rate of evolution in transcription factor binding sites. BMC evolutionary biology 3:19/1-13. 12946282 en http://dx.doi.org/10.1186/1471-2148-3-19 BMC Evolutionary Biology Creative Commons Attribution Moses et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Artifacts Base composition Base sequence Binding sites, genetics Computational biology, methods Computational biology, statistics & numerical data Conserved sequence Evolution, molecular Gene expression regulation, fungal Genetic variation Genome, fungal Mutagenesis Predictive value of tests Promoter regions, genetic Promoter regions, genetic, physiology Saccharomyces, genetics Saccharomyces cerevisiae, genetics Transcription factors, genetics Transcription factors, metabolism Transcription, genetic Kellis, Manolis Moses, Alan M. Chiang, Derek Y. Eisen, Michael B. Lander, Eric Steven Position specific variation in the rate of evolution in transcription factor binding sites |
| title | Position specific variation in the rate of evolution in transcription factor binding sites |
| title_full | Position specific variation in the rate of evolution in transcription factor binding sites |
| title_fullStr | Position specific variation in the rate of evolution in transcription factor binding sites |
| title_full_unstemmed | Position specific variation in the rate of evolution in transcription factor binding sites |
| title_short | Position specific variation in the rate of evolution in transcription factor binding sites |
| title_sort | position specific variation in the rate of evolution in transcription factor binding sites |
| topic | Artifacts Base composition Base sequence Binding sites, genetics Computational biology, methods Computational biology, statistics & numerical data Conserved sequence Evolution, molecular Gene expression regulation, fungal Genetic variation Genome, fungal Mutagenesis Predictive value of tests Promoter regions, genetic Promoter regions, genetic, physiology Saccharomyces, genetics Saccharomyces cerevisiae, genetics Transcription factors, genetics Transcription factors, metabolism Transcription, genetic |
| url | http://hdl.handle.net/1721.1/59308 |
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