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Copyright2017HeatherAllen DepartmentofBiologicalSciencesSeminarBlog SeminarDate:2/17/17 Speaker:Dr.VaughnCooper,UniversityofPittsburgh Title:“Whymutationratesvaryamongspeciesandwithingenomes.” LOCATIONMATTERS:THEPRESERVATIONOFIMPORTANT BACTERIALGENESINRAPIDLYMUTATINGCHROMOSOMES By:HeatherAllen(BiologyPhDStudent) Dr.VaughnCooperisarelativelyrecentadditiontotheUniversityof Pittsburgh,havingjoinedtheDepartmentofMicrobiologyand MolecularGeneticsinthefallof2015fromtheUniversityofNew Hampshire.Hislabstudies“evolutioninaction”bylookingat adaptationsofdifferentbacterialpopulations,especiallyinthe formationofbiofilmsandthedevelopmentofmulticellularityin bacterialcommunities.AlthoughDr.Cooperoftenpresentshisresearch intheareaofbiofilms,hewasexcitedtodiscusshisworkonthe differentialevolutionrateofgenomeregionsinstead.Theoverallgoal ofstudyingdifferentialmutationratesistobeabletopredictwhat causesthesemutationsandhowtheyhappen.Understandingthis evolutionofbacterialgenomeswillhopefullyallowforbettertreatment ofthediseasestheycauseaswellasgiveusanewangletounderstand evolution. AftermeetingDr.Cooperoverlunch,itwasnosurprisethathis dynamicpersonalitycarriedoverintohistalk.ThoughIamnotusually muchofamicrobiologypersonwhogetsexcitedaboutbacteria,itwas hardnottogetcaughtupintheexcitementheexudedashediscussed thedifferentialmutationratesacrossspeciesofbacteriaandeven withinbacteriabutacrosschromosomes.Hisworkiscenteredaround performingevolutionaryexperiments,suchasmutationaccumulation, indifferentstrainsofbacteriawithmultiplechromosomesand Copyright2017HeatherAllen comparingthemutationratesbetweenstrains.Mutationaccumulation experimentsinvolvegrowingbacteriaandallowingthemtomutateand evolve,selectingthenewmutantsandtransferringthemtonewmedia inordertoallowthemtogrowandmutateagain.Thisprocessiscarried outrepeatedlyuntilallmutationsareexhaustedandthebacteria ceasestogeneratenewmutations.Eachnewmutantcanthenbe sequencedinordertoidentifythespecificmutationsgainedbetween eachstep.Iamnostrangertothetediumofbacterialevolution experiments,asIhavespentmyspringrotationprojecthereat Duquesnedoingtheexactsamething!ThoughIhaven’tquitereached thestagewhereIcarryoutmutationaccumulationexperimentsfor multiplebacterialstrainsandsequencethegenomeofeveryoneofthe hundredsofmutantsIgenerateandcomparethemyet,ofcourse. Althoughnewtome,itisalreadywellknownthatinbacterialspecies withmultiplechromosomes,theprimarychromosomeislargerand carriesmostoftheessentialgenesthatarewellconservedwhereasthe secondaryoneissmallerandcontainsfewerconservedgenes. Additionally,replicationiscoordinatedsothatbothchromosomes terminatereplicationatthesametime,meaningthatreplicationofthe secondarychromosomeisinitiatedaftertheinitiationoftheprimary chromosome.Itturnsoutthat‘latereplicated’genesineither chromosomemutatemorerapidly,whereasonesclosertotheoriginof replicationarebetterpreserved.Itseemsthatthegenesclosertothe originareamongthemostvitaltocellsurvivalandproliferation, perhapsexplainingtheirtendencytobesowellconserved.Dr.Cooper’s hopewastodiscoveriftherewerechromosomalbiasesbetween primaryandsecondarychromosomesinmutationrates,andevenif therewasregionalvariationofmutationrateswithinchromosomes. Themutationaccumulationprojectfoundthatnotonlydomutation ratesvaryacrossthethreedifferentspeciestested(Burkholderia cenocepacia,Vibriocholerae,andVibriofischeri),butitalsovaries Copyright2017HeatherAllen betweenchromosomeswithinthesamespecies.Evidencesuggested thatmutationratesmaybeperiodic-themutationsseemedtohappen inthesamespotsoneithersideofthebi-directionallyreplicating circularchromosome.Furthermore,thesecondarychromosomes showedthesamepatternofperiodicmutations.Whattheseperiodic mutationratesmean,though,isnotyetclear.Secondarychromosomes asawholehaveamuchhigherrateofmutation,butyetagainthe reasonisnotsolidlydefined.Perhapssecondarychromosomesare predisposedtoevolvemorequicklybecausetheycontaingenesthat naturallyevolvemorequickly(i.e.fewerhousekeepinggenes).Or maybetheyevolvemorequicklybecausesimplybecausethereisa fluctuationineitherfidelityorrepairrelatedtoreplicationtiming. Eitherway,itisobviousthatlocationmatters:differentgenomeregions evolveatdifferentrates,anditislikelythatgenesarecompeting evolutionarilyforoptimalregionsinordertobehighlyexpressedand avoidmutations. Mutationratesamongchromosomesandadaptationsinbiofilmsare notDr.Cooper’sonlyscientificinterests,though.Inspeakingtohim bothatlunchandatthesocialafterseminar,histruepassion,it seemed,ishiscommunityoutreachprogram,EvolvingSTEM.The programinvolvesusingbacteriatoteachevolutionarybiologyinhigh schools.Inthecourseofjustoveraweek,highschoolersareableto carryoutabacterialevolutionexperimentthatshowsobservable evolutionhappeninginrealtime.Dr.Cooper’sprogramnotonly introduceshighschoolerstoperformingrealscience,butithasalso beenshowntoimprovetestscoresassessingtheirunderstanding evolution.Doinggreatscienceandpublishinginhighimpactjournalsis allwellandgood,butIfeellikebeingagoodscientistnowdays requiresmore.Communicatingyourscienceisimportant,yes,buteven moreimportantisusingyoursciencetomakeadifference,whetherit’s workingtoeducateascientificallyinexperiencedpublic,lobbyingto politiciansresponsibleformakinglawsbasedonscientificknowledge, Copyright2017HeatherAllen orbringingtheexcitementofscienceanddiscoverytostudentsand encouragingthemstartthinkingscientifically.