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Adaptive Evolution of Conserved Noncoding Elements in Mammals 英文参考文献
AdaptiveEvolutionofConserved
NoncodingElementsinMammals
SuYeon Kim1*,Jonathan K. Pritchard2*
1Department ofStatistics, TheUniversityofChicago, Chicago, Illinois,United States ofAmerica, 2Department ofHuman Genetics,TheUniversity ofChicago,Chicago,
Illinois,UnitedStatesofAmerica
Conservednoncodingelements(CNCs)areanabundantfeatureofvertebrategenomes.SomeCNCshavebeenshown
toactascis-regulatorymodules,butthefunctionofmostCNCsremainsunclear.TostudytheevolutionofCNCs,we
havedevelopedastatisticalmethodcalledthe‘‘sharedratestest’’toidentifyCNCsthatshowsignificantvariationin
substitutionratesacrossbranchesofaphylogenetictree.Wereportanapplicationofthismethodtoalignmentsof
98,910 CNCs from the human, chimpanzee, dog, mouse, and rat genomes. We find that ;68% of CNCs evolve
accordingtoanullmodelwhere,foreachCNC,asingleparametermodelsthelevelofconstraintactingthroughoutthe
phylogenylinkingthesefivespecies.Theremaining;32%ofCNCsshowdeparturesfromthebasicmodelincluding
speed-upsandslow-downsonparticularbranchesandoccasionallymultipleratechangesondifferentbranches.We
findthatasubsetofthesignificantCNCshaveevolvedsignificantlyfasterthanthelocalneutralrateonaparticular
branch, providing strong evidence for adaptive evolution in these CNCs. The distribution of these signals on the
phylogeny suggests that adaptive evolution of CNCs occurs in occasional short bursts of evolution. Our analyses
suggestalargesetofpromisingtargetsforfuturefunctionalstudiesofadaptation.
Citation:KimSY,PritchardJK(2007)Adaptiveevolutionofconservednoncodingelementsinmammals.PLoSGenet3(9):e147.doi:10.1371/journal.pgen.0030147
manyserveashighlyconservedregulatorsofthesefunction-
allyconservedgenes[13].
Introduction
Phenotypicevolutionproceedsbothbychangesinprotein
coding sequences and by changes in gene expression that
determine when, where, and how much genes are expressed
[1–3]. Although recent genome-wide studies have begun the
process of identifying genes that show signals of adaptive
evolutionincodin
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