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dc.contributor.authorKellis, Manolis
dc.contributor.authorMoses, Alan M.
dc.contributor.authorChiang, Derek Y.
dc.contributor.authorEisen, Michael B.
dc.contributor.authorLander, Eric Steven
dc.date.accessioned2010-10-14T12:33:24Z
dc.date.available2010-10-14T12:33:24Z
dc.date.issued2003-08
dc.date.submitted2003-05
dc.identifier.issn1471-2148
dc.identifier.urihttp://hdl.handle.net/1721.1/59308
dc.description.abstractBackground: 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.en_US
dc.description.sponsorshipUnited States. Dept. of Energy (contract no. ED-AC03-76SF00098)en_US
dc.publisherBioMed Central Ltden_US
dc.relation.isversionofhttp://dx.doi.org/10.1186/1471-2148-3-19en_US
dc.rightsCreative Commons Attributionen_US
dc.sourceBioMed Central Ltden_US
dc.subjectArtifactsen_US
dc.subjectBase compositionen_US
dc.subjectBase sequenceen_US
dc.subjectBinding sites, geneticsen_US
dc.subjectComputational biology, methodsen_US
dc.subjectComputational biology, statistics & numerical dataen_US
dc.subjectConserved sequenceen_US
dc.subjectEvolution, molecularen_US
dc.subjectGene expression regulation, fungalen_US
dc.subjectGenetic variationen_US
dc.subjectGenome, fungalen_US
dc.subjectMutagenesisen_US
dc.subjectPredictive value of testsen_US
dc.subjectPromoter regions, geneticen_US
dc.subjectPromoter regions, genetic, physiologyen_US
dc.subjectSaccharomyces, geneticsen_US
dc.subjectSaccharomyces cerevisiae, geneticsen_US
dc.subjectTranscription factors, geneticsen_US
dc.subjectTranscription factors, metabolismen_US
dc.subjectTranscription, geneticen_US
dc.titlePosition specific variation in the rate of evolution in transcription factor binding sitesen_US
dc.typeSoftwareen_US
dc.identifier.citationMoses, 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.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Laboratory for Computer Scienceen_US
dc.contributor.mitauthorKellis, Manolis
dc.contributor.mitauthorLander, Eric S.
dc.relation.journalBMC Evolutionary Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.identifier.pmid12946282
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2010-09-03T16:06:53Z
dc.language.rfc3066en
dc.rights.holderMoses et al.; licensee BioMed Central Ltd.
dspace.orderedauthorsMoses, Alan M; Chiang, Derek Y; Kellis, Manolis; Lander, Eric S; Eisen, Michael Ben
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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