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Transcript
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.