Experimental Relocation of the Mitochondrial ATP9 Gene to the Nucleus Reveals Forces Underlying Mitochondrial Genome Evolution 英文参考文献.docVIP

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Experimental Relocation of the Mitochondrial ATP9 Gene to the Nucleus Reveals Forces Underlying Mitochondrial Genome Evolution 英文参考文献.doc

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Experimental Relocation of the Mitochondrial ATP9 Gene to the Nucleus Reveals Forces Underlying Mitochondrial Genome Evolution 英文参考文献

ExperimentalRelocationoftheMitochondrialATP9Gene totheNucleusRevealsForcesUnderlyingMitochondrial GenomeEvolution Ma?¨lisBietenhader1,2.,AlexandreMartos1,2.,EmmanuelTetaud1,2.,RaekaS.Aiyar3.,CaroleH.Sellem4, RozaKucharczyk1,2,SandraClauder-Mu¨nster3,Marie-FranceGiraud1,2,Franc?oisGodard1,2 Be′ne′dicteSalin1,2,IsabelleSagot1,2,JulienGagneur3,MichelleDe′quard-Chablat5,6, , Ve′roniqueContamine5,6,SylvieHermann-LeDenmat5,6,7,AnnieSainsard-Chanet4,LarsM.Steinmetz3*, Jean-PauldiRago1,2 * 1Universite′ Bordeaux,IBGC,UMR5095CNRS,Bordeaux,France,2CNRS,IBGC,UMR5095CNRS,Bordeaux,France,3GenomeBiologyUnit,EuropeanMolecularBiology Laboratory(EMBL),Heidelberg,Germany,4Universite′ Paris-Sud,CentredeGe′ne′tiqueMole′culaire, UPR3404,CNRS,Gif-sur-Yvette,France,5Universite′ Paris-Sud,Institut deGe′ne′tiqueetMicrobiologie,UMR8621,Orsay,France,6CNRS,Orsay,France,7EcoleNormaleSupe′rieure,Paris,France Abstract Only a few genes remain in the mitochondrial genome retained by every eukaryotic organism that carry out essential functions and are implicated in severe diseases. Experimentally relocating these few genes to the nucleus therefore has boththerapeuticandevolutionaryimplications.Numerousunproductiveattemptshavebeenmadetodoso,withatotalof only 5 successes across all organisms. We have taken a novel approach to relocating mitochondrial genes that utilizes naturallynuclearversionsfromotherorganisms.Wedemonstratethisapproachonsubunit9/cofATPsynthase,successfully relocating this gene for the first time in any organism by expressing the ATP9 genes from Podospora anserina in Saccharomycescerevisiae.Thisstudysubstantiatestheroleofproteinstructureinmitochondrialgenetransfer:expressionof chimeric constructs reveals that the P. anserina proteins can be correctly imported into mitochondria due to reduced hydrophobicityofthefirsttransmembranesegment.NuclearexpressionofATP9,whilepermittingalmostfullyfunctional oxidativephosphorylation,perturbsmanycellularproperties,includingcellularmorphology