Evolution of Regulatory Sequences in 12 Drosophila Species 英文参考文献.docVIP

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2017-05-11 发布于上海
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Evolution of Regulatory Sequences in 12 Drosophila Species 英文参考文献.doc

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Evolution of Regulatory Sequences in 12 Drosophila Species 英文参考文献

EvolutionofRegulatorySequencesin12Drosophila Species JaebumKim.,XinHe.,SaurabhSinha* DepartmentofComputerScience,UniversityofIllinoisatUrbana-Champaign,Urbana,Illinois,UnitedStatesofAmerica Abstract Characterizationoftheevolutionaryconstraintsactingoncis-regulatorysequencesiscrucialtocomparativegenomicsand provideskeyinsightsontheevolutionoforganismaldiversity.Westudytherelationshipsamongorthologouscis-regulatory modules(CRMs)in12Drosophilaspecies,especiallywithrespecttotheevolutionoftranscriptionfactorbindingsites,and report statistical evidence in favor of key evolutionary hypotheses. Binding sites are found to have position-specific substitutionrates.However,theselectiveforcesatdifferentpositionsofasitedonotactindependently,andtheevidence suggeststhatconstraintsonsitesareoftenbasedontheirexactbindingaffinities.Bindingsitelossisseentoconformtoa molecularclockhypothesis.Therateofsitelossistranscriptionfactor–specificanddependsonthestrengthofbindingand, in some cases, the presence of other binding sites in close proximity. Our analysis is based on a novel computational method for aligning orthologous CRMs on a tree, which rigorously accounts for alignment uncertainties and exploits binding site predictions through a unified probabilistic framework. Finally, we report weak purifying selection on short deletions, providingimportant clues about overallspatial constraintson CRMs. Ourresults present a complexpicture of regulatorysequenceevolution,withsubstantialplasticitythatdependsonanumberoffactors.Theinsightsgainedinthis studywillhelpustounderstandthecombinatorialcontrolofgeneregulationandhowitevolves.Theywillpavethewayfor theoreticalmodelsthatarecognizantoftheimportantdeterminantsofregulatorysequenceevolutionandwillbecriticalin genome-wideidentificationofnon-codingsequencesunderpurifyingorpositiveselection. Citation:KimJ,HeX,SinhaS(2009)EvolutionofRegulatorySequencesin12DrosophilaSpecies.PLoSGenet5(1):e1000330.doi:10.1371/journal.pgen.1000330 Editor:TakashiGojobori,N