Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction 英文参考文献.docVIP

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Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction 英文参考文献.doc

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Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction 英文参考文献

EvolutionaryPressureonMitochondrialCytochromebIs ConsistentwithaRoleofCytbI7TAffectingLongevity duringCaloricRestriction WesleyA.Beckstead1¤a,MarkT.W.Ebbert1¤b,MarkJ.Rowe2,DavidA.McClellan1¤c* 1Department of Biology, Brigham Young University, Provo, Utah, United States of America, 2Department of Nutrition, Dietetics, and Food Science, Brigham Young University,Provo,Utah,UnitedStatesofAmerica Abstract Background:Metabolismofenergynutrientsbythemitochondrialelectrontransportchain(ETC)isimplicatedintheaging process.PolymorphismsincoreETCproteinsmayhaveaneffectonlongevity.Hereweinvestigatethecytochromeb(cytb) polymorphismataminoacid7(cytbI7T)thatdistinguisheshumanmitochondrialhaplogroupHfromhaplogroupU. PrincipalFindings:Wecomparedlongevityofindividualsinthesetwohaplogroupsduringhistoricalextremesofcaloric intake.HaplogroupHexhibitssignificantlyincreasedlongevityduringhistoricalcaloricrestrictioncomparedtohaplogroup U (p=0.02) while during caloric abundance they are not different. The historical effects of natural selection on the cytb protein were estimated with the software TreeSAAP using a phylogenetic reconstruction for 107 mammal taxa from all major mammalian lineages using 13 complete protein-coding mitochondrial gene sequences. With this framework, we comparedthebiochemicalshiftsproducedbycytbI7Twithhistoricalevolutionarypressureonandnearthispolymorphic site throughout mammalian evolution to characterize the role cytbI7T had on the ETC during times of restricted caloric intake. Significance: Our results suggest the relationship between caloric restriction and increased longevity in human mitochondrialhaplogroupHisdeterminedbycytbI7TwhichlikelyenhancestheabilityofwatertoreplenishtheQibinding siteanddecreasesthetimeubisemiquinoneisattheQosite,resultinginadecreaseintheaverageproductionrateofradical oxygenspecies(ROS). Citation:BecksteadWA,EbbertMTW,RoweMJ,McClellanDA(2009)EvolutionaryPressureonMitochondrialCytochromebIsConsistentwithaRoleofCytbI7T AffectingLongev