Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes 英文参考文献.docVIP

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Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes 英文参考文献.doc

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Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes 英文参考文献

DissectingtheGeneNetworkofDietaryRestrictionto IdentifyEvolutionarilyConservedPathwaysandNew FunctionalGenes DanielWuttke1,RichardConnor2,ChintanVora1,ThomasCraig1,YangLi1¤,ShonaWood1,OlgaVasieva3, RobertShmooklerReis4,5,FushengTang2*,Joa?oPedrodeMagalha?es1* 1Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom, 2Department of Biology, University of Arkansas,LittleRock,Arkansas,UnitedStatesofAmerica,3InstituteofIntegrativeBiology,UniversityofLiverpool,Liverpool,UnitedKingdom,4CentralArkansasVeterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America, 5Department of Geriatrics and Department of BiochemistryandMolecularBiology,UniversityofArkansasforMedicalSciences,LittleRock,Arkansas,UnitedStatesofAmerica Abstract Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extendslifespaninmultipleorganisms.Theconservedlife-extendingeffectofDRsuggeststheinvolvementoffundamental mechanisms,althoughtheseremainasubjectofdebate.Tohelpdecipherthelife-extendingmechanismsofDR,wefirst compiledalistofgenesthatifgeneticallyaltereddisruptorpreventthelife-extendingeffectsofDR.WecalledtheseDR– essentialgenesandidentifiedmorethan100inmodelorganismssuchasyeast,worms,flies,andmice.Inorderforother researcherstobenefitfromthisfirstcuratedlistofgenesessentialforDR,weestablishedanonlinedatabasecalledGenDR (/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extendingmechanisms,wethenusedavarietyofnetworkandsystemsbiologyapproachestoanalyzethegene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR– essential genes. In budding yeast, we predicted nine genes related to vacuolar functi