Oscillating Evolution of a Mammalian Locus with Overlapping Reading Frames An XLαsALEX Relay 英文参考文献.docVIP

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Oscillating Evolution of a Mammalian Locus with Overlapping Reading Frames An XLαsALEX Relay 英文参考文献.doc

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Oscillating Evolution of a Mammalian Locus with Overlapping Reading Frames An XLαsALEX Relay 英文参考文献

OscillatingEvolutionofaMammalianLocus withOverlappingReadingFrames: AnXLas/ALEXRelay Anton Nekrutenko1,2,3*,Samir Wadhawan1,2,3,Paula Goetting-Minesky2,4,Kateryna D.Makova4 1 Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America 2 Center for Comparative GenomicsandBioinformatics,PennsylvaniaStateUniversity,UniversityPark,Pennsylvania,UnitedStatesofAmerica3TheHuckInstitutesforLifeSciences,Pennsylvania StateUniversity,UniversityPark,Pennsylvania,UnitedStatesofAmerica4DepartmentofBiology,PennsylvaniaStateUniversity,UniversityPark,Pennsylvania,UnitedStates ofAmerica XLasandALEXarestructurallyunrelatedmammalianproteinstranslatedfromalternativeoverlappingreadingframes ofasingletranscript.Notonlyaretheyencodedbythesamelocus,butaspecificXLas/ALEXinteractionisessentialfor G-protein signaling in neuroendocrine cells. A disruption of this interaction leads to abnormal human phenotypes, includingmentalretardationandgrowthdeficiency.Theregionofoverlapbetweenthetworeadingframesevolvesat aremarkablespeed:thedivergencebetweenhumanandmouseALEXpolypeptidesmakesthemvirtuallyunalignable. Totracetheevolutionofthispuzzlinglocus,wesequenceditinapes,OldWorldmonkeys,andaNewWorldmonkey. Weshowthattheoverlapbetweenthetworeadingframesandthephysicalinteractionbetweenthetwoproteinsforce thelocustoevolveinanunprecedentedway.Namely,tomaintaintwooverlappingprotein-codingregionsthelocusis forcedtohavehighGCcontent,whichsignificantlyelevatesitsintrinsicevolutionaryrate.However,thetwoencoded proteinscannot afford to changetooquickly relative toeach otherasthis mayimpairtheir interaction andlead to severephysiologicalconsequences.AsaresultXLasandALEXevolveinanoscillatingfashionconstantlybalancingthe ratesofaminoacidreplacements.Thisisthefirstexampleofarapidlyevolvinglocusencodinginteractingproteinsvia overlappingreadingframes,withapossiblelinktotheoriginofspecies-specificneurologicaldifferences. Citation:Nekrutenko