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Non-Silent Story on Synonymous Sites in Voltage-Gated Ion Channel Genes 英文参考文献
Non-SilentStoryonSynonymousSitesinVoltage-Gated
IonChannelGenes
TongZhou1,2.,EunA.Ko3.,WanjunGu4,InjaLim5,HyoweonBang5,Jae-HongKo5*
1InstituteforPersonalizedRespiratoryMedicine,UniversityofIllinoisatChicago,Chicago,Illinois,UnitedStatesofAmerica,2SectionofPulmonary,CriticalCare,Sleep
Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America, 3Department of Medicine, University of California San
Francisco,SanFrancisco,California,UnitedStatesofAmerica,4KeyLaboratoryofChildDevelopmentandLearningScienceofMinistryofEducationofChina,Southeast
University,Nanjing,Jiangsu,China,5DepartmentofPhysiology,CollegeofMedicine,Chung-AngUniversity,Seoul,SouthKorea
Abstract
Synonymousmutationsareusuallyreferredtoas‘‘silent’’,butincreasingevidenceshowsthattheyarenotneutralinawide
rangeoforganisms.Welookedintotherelationshipbetweensynonymouscodonusagebiasandresidueimportanceof
voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are
associatedwithtransmembraneorchannel-formingregions,i.e.,thesitesthatareparticularlylikelytobeinvolvedinthe
closingandopeningofanionchannel.Ourhypothesisisthattranslationallyoptimalcodonsarepreferredatthesiteswithin
transmembranedomainsorchannel-formingregionsinvoltage-gatedionchannelgenestoavoidmistranslation-induced
proteinmisfoldingorloss-of-function.UsingtheMantel-Haenszelprocedure,whichappliestocategoricaldata,wefound
that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in
channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is
significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in
voltage-gatedionchannelgenesarenotneutral.Silentmutationsatchannel-relatedsitesmayleadtodysfunctionofthe
ionchannel.
Citation:ZhouT,KoEA,GuW,LimI,BangH,etal.(2012)Non-SilentStoryonSynonym
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