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1、BasicScienceforCliniciansEvolutionaryGeneticsofCoronaryHeartDiseaseKeyueDing,PhD;IftikharJ.Kullo,MDNothinginbiologymakessenseexceptinthelightofmaybeaffectedbynaturalselection16;conversely,regionsoftheevolution.1humangenomeundernaturalselection17arelike
2、lytoharbor—TheodosiusDobzhanksy,1973functionalloci(genecodingandregulatoryregions18)thatmayinfluencediseasesusceptibility.Inferencesaboutnaturalselec-Nobiologicalproblemissolveduntilboththeprox-tionmaythereforehelpidentifydiseasesusceptibilitylociinima
3、teandtheevolutionarycausationhasbeeneluci-humansandfacilitatediseasemappingstudies.19dated.Furthermore,thestudyofevolutionarycausesInthisreview,wediscussthecurrenthypothesesandisaslegitimateapartofbiologyasisthestudyoftheknowledgeabouttheevolutionaryge
4、neticsofseveralriskusuallyphysico-chemicalproximatecauses.2factorsforCHD,includinghypertension,dyslipidemia,and—ErnstW.Mayr,1982themetabolicsyndrome.Severalcandidategenesinpathwaysofbloodpressure,glucoseandlipidmetabolism,bloodSusceptibilitytocommondis
5、easessuchascoronaryheartcoagulation,andinflammationthatmaybeundernaturaldisease(CHD)mayinpartreflecthistoricalorevolutionaryselectionareenumerated.Anevolutionaryperspectivemightlegacies,3,4andinterestinstudyingevolutionarybiologytoexplainwhycontemporar
6、yhumansareathighriskforCHDandgainnovelinsightsintohumanhealthanddiseaseisincreas-alsohelpstobetterunderstandvariationindiseasesusceptibility.ing.TheevolutionaryhistoryofthehumanspeciesmayprovidevaluableinsightsintotheoriginofcommondiseasesNaturalSelect
7、ionbeyondwhatispossiblebyinvestigatingonlythemostNaturalselectionistheinevitableconsequenceofinheritedimmediateor“proximal”causesofdisease.Thepotentialrolevariationinfitness,whichisdefinedastherelativeabilityofofevolutionarybiologyinexplainingdiseaseca
8、usationwasanorganismtosurviveandtransmititsgenestothenexthighlightedbyWilliamsandNesse3andisoftenreferredtoasgeneration.20Undernaturalselection,individualswithadvan-darwinianmedicine.Althoughtherelevanceofanevolution-tageousor“adaptive”