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1、RishishwarandJordanBMCGenomics(2017)18:140DOI10.1186/s12864-017-3539-3RESEARCHARTICLEOpenAccessImplicationsofhumanevolutionandadmixtureformitochondrialreplacementtherapy1,2,31,2,3*LavanyaRishishwarandI.KingJordanAbstractBackground:Mitochondrialreplacement(MR)therapyisanewassisted
2、reproductivetechnologythatallowswomenwithmitochondrialdisorderstogivebirthtohealthychildrenbycombiningtheirnucleiwithmitochondriafromunaffectedeggdonors.EvolutionarybiologistshaveraisedconcernsaboutthesafetyofMRtherapybasedontheextenttowhichnuclearandmitochondrialgenomesareobserv
3、edtoco-evolvewithinnaturalpopulations,i.e.thenuclear-mitochondrialmismatchhypothesis.Insupportofthishypothesis,anumberofpreviousstudiesonmodelorganismshaveprovidedevidenceforincompatibilitybetweennuclearandmitochondrialgenomesfromdivergentpopulationsofthesamespecies.Results:Wetes
4、tedthenuclear-mitochondrialmismatchhypothesisforhumansbyobservingtheextentofnaturallyoccurringnuclear-mitochondrialmismatchseenfor2,504individualsacross26populations,from5continentalpopulationsgroups,characterizedaspartofthe1000GenomesProject(1KGP).Wealsoperformedareplicationanal
5、ysisonmitochondrialDNA(mtDNA)haplotypesfor1,043individualsfrom58populations,characterizedaspartoftheHumanGenomeDiversityProject(HGDP).NuclearDNA(nDNA)andmtDNAsequencesfromthe1KGPweredirectlycomparedwithinandbetweenpopulations,andthepopulationdistributionsofmtDNAhaplotypesderivedf
6、rombothsequence(1KGP)andgenotype(HGDP)datawereevaluated.LevelsofnDNAandmtDNApairwisesequencedivergencearehighlycorrelated,consistentwiththeirco-evolutionamonghumanpopulations.However,therearenumerouscasesofco-occurrenceofnuclearandmitochondrialgenomesfromdivergentpopulationswithi
7、nindividualhumans.Furthermore,pairsofindividualswithcloselyrelatednucleargenomescanhavehighlydivergentmtDNAhaplotypes.Supposedlymismatchednuclear-mitochondrialgenomecombinationsarefoundnotonlywithinindividualsfrompopulationsknowntobeadmixed,wheretheymaybeexpected,butalsofrompopul
8、ationswithlowoveralllevelsofobservedadmi
