01 an introduction to genetic analysis.docx
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01anintroductiontogeneticanalysis
Chapter1
GeneticsandtheOrganism
KeyConcepts
ThehereditarymaterialisDNA.
DNAisadoublehelixcomposedoftwointertwinednucleotidechainsorientedinoppositedirections.
InthecopyingofDNA,thechainsseparateandserveasmoldsformakingtwoidenticaldaughterDNAmolecules.
ThefunctionalunitsofDNAaregenes.
AgeneisasegmentofDNAthatcanbecopiedtomakeRNA.
ThenucleotidesequenceinRNAistranslatedintotheaminoacidsequenceofaprotein.
Proteinsarethemaindeterminantsofthebasicstructuralandphysiologicalpropertiesofanorganism.
Thecharacteristicsofaspeciesareencodedbyitsgenes.
Variationwithinaspeciesmaybefromhereditaryvariation,environmentalvariation,orboth.
Hereditaryvariationiscausedbyvariantformsofgenes(alleles).
Introduction
Whystudygenetics?
Therearetwobasicreasons.First,geneticsoccupiesapivotalpositionintheentiresubjectofbiology.Therefore,foranyseriousstudentofplant,animal,ormicrobiallife,anunderstandingofgeneticsisessential.Second,genetics,likenootherscientificdiscipline,iscentraltonumerousaspectsofhumanaffairs.Ittouchesourhumanityinmanydifferentways.Indeed,geneticissuesseemtosurfacedailyinourlives,andnothinkingpersoncanaffordtobeignorantofitsdiscoveries.Inthischapter,wetakeanoverviewofthescienceofgenetics,showinghowithascometooccupyitscrucialposition.Inaddition,weprovideaperspectivefromwhichtoviewthesubsequentchapters.
First,weneedtodefinewhatgeneticsis.Somedefineitasthestudyofheredity,buthereditaryphenomenawereofinteresttohumanslongbeforebiologyorgeneticsexistedasthescientificdisciplinesthatweknowtoday.Ancientpeopleswereimprovingplantcropsanddomesticatedanimalsbyselectingdesirableindividualsforbreeding.Theyalsomusthavepuzzledabouttheinheritanceofindividualityinhumansandaskedsuchquestionsas,“Whydochildrenresembletheirparents?
”and“Howcanvariousdiseasesruninfamilies?
”Butthesepeoplecouldnotbecalledgeneticists.Geneticsasasetofprinciplesandanalyticalproceduresdidnotbeginuntilthe1860s,whenanAugustinianmonknamedGregorMendel(Figure1-1)performedasetofexperimentsthatpointedtotheexistenceofbiologicalelementsthatwenowcallgenes.Thewordgeneticscomesfromtheword“gene,”andgenesarethefocusofthesubject.Whethergeneticistsstudyatthemolecular,cellular,organismal,family,population,orevolutionarylevel,genesarealwayscentralintheirstudies.Simplystated,geneticsisthestudyofgenes.
Whatisagene?
Ageneisasectionofathreadlikedoublehelicalmoleculecalleddeoxyribonucleicacid,abbreviatedDNA.Thediscoveryofgenesandunderstandingtheirmolecularstructureandfunctionhavebeensourcesofprofoundinsightintotwoofthebiggestmysteriesofbiology:
1.Whatmakesaspecieswhatitis?
Weknowthatcatsalwayshavekittensandpeoplealwayshavebabies.Thiscommon-senseobservationnaturallyleadstoquestionsaboutthedeterminationofthepropertiesofaspecies.Thedeterminationmustbehereditarybecause,forexample,theabilitytohavekittensisinheritedbyeverygenerationofcats.
2.Whatcausesvariationwithinaspecies?
Wecandistinguisheachotheraswellasourownpetcatfromothercats.Suchdifferenceswithinaspeciesrequireexplanation.Someofthesedistinguishingfeaturesareclearlyfamilial;forexample,animalsofacertainuniquecoloroftenhaveoffspringwiththesamecolor,and,inhumanfamilies,certainfeaturessuchastheshapeofthenosedefinitely“runinthefamily.”Hencewemightsuspectthatahereditarycomponentexplainsatleastsomeofthevariationwithinaspecies.
Theanswertothefirstquestionisthatgenesdictatetheinherentpropertiesofaspecies.Theproductsofmostgenesarespecificproteins.Proteinsarethemainmacromoleculesofanorganism.Whenyoulookatanorganism,whatyouseeiseitherproteinorsomethingthathasbeenmadebyaprotein.Theaminoacidsequenceofaproteinisencodedinagene.Thetimingandrateofproductionofproteinsandothercellularcomponentsareafunctionbothofthegeneswithinthecellsandoftheenvironmentinwhichtheorganismisdevelopingandfunctioning.
Theanswertothesecondquestionisthatanyonegenecanexistinseveralformsthatdifferfromeachother,generallyinsmallways.Theseformsofagenearecalledalleles.Allelicvariationcauseshereditaryvariationwithinaspecies.Attheproteinlevel,allelicvariationbecomesproteinvariation.
Thenexttwosectionsshowhowgenesinfluencetheinherentpropertiesofaspeciesandhowallelicvariationcontributestovariationwithinaspecies.Thesesectionsareanoverview;mostofthedetailswillbepresentedinlaterchapters.
Genesasdeterminantsoftheinherentpropertiesofspecies
Whatisthenatureofgenes,andhowdotheyperformtheirbiologicalroles?
ThreefundamentalpropertiesarerequiredofgenesandtheDNAofwhichtheyarecomposed.
1.Replication.Hereditarymoleculesmustbecapableofbeingcopiedattwokeystagesofthelifecycle(Figure1-2).Thefirststageistheproductionofthecelltypethatwillensurethecontinuationofaspeciesfromonegenerationtothenext.Inplantsandanimals,thesecellsarethegametes:
eggandsperm.Theotherstageiswhenthefirstcellofaneworganismundergoesmultipleroundsofdivisiontoproduceamulticellularorganism.Inplantsandanimals,thisisthestageatwhichthefertilizedegg,thezygote,dividesrepeatedlytoproducethecomplexorganismalappearancethatwerecognize.
2.Generationofform.Theworkingstructuresthatmakeupanorganismcanbethoughtofasformorsubstance.Lookedatinthisway,DNAhasessential“information”;inotherwords,“thatwhichisneededtogiveform.”
3.Mutation.Agenethathaschangedfromoneallelicformintoanotherhasundergonemutation–aneventthathappensrarelybutregularly.Mutationisnotonlyabasisforvariationwithinaspecies,but,overthelongterm,alsotherawmaterialforevolution.
DNAanditsreplication
Anorganism'sbasiccomplementofDNAiscalleditsgenome.Thebodycellsofmostplantsandanimalscontaintwogenomes(Figure1-3).Theseorganismsarediploid.Thecellsofmostfungi,algae,andbacteriacontainjustonegenome.Theseorganismsarehaploid.ThegenomeitselfismadeupofoneormoreextremelylongmoleculesofDNAthatareorganizedintochromosomes.Forinstance,humanbodycellscontaintwosetsof23chromosomes,foratotalof46.GenesaresimplythefunctionalregionsofchromosomalDNA.Eachchromosomeinthegenomecarriesadifferentarrayofgenes.Indiploidcells,eachchromosomeanditscomponentgenesarepresenttwice.Twochromosomeswiththesamegenearrayaresaidtobehomologous.Whenacelldivides,allthechromosomes(oneortwogenomes)arereplicated;soeachdaughtercellcontainsthefullcomplement.Therefore,theunitofreplicationisthechromosome;whenachromosomeisreplicated,allthegenesofthatchromosomeareautomaticallyreplicatedalongwithit.
Tounderstandreplication,weneedtounderstandthebasicnatureofDNA.DNAisalinear,double-helicalstructurelookingratherlikeamolecularspiralstaircase.Thedoublehelixiscomposedoftwointertwinedchainsofbuildingblockscallednucleotides.Eachnucleotideconsistsofaphosphategroup,adeoxyribosesugarmolecule,andoneoffourdifferentnitrogenousbaseseitheradenine,guanine,cytosine,orthymine.Eachofthefournucleotidesisusuallydesignatedbythefirstletterofthebasethatitcontains:
A,G,C,orT.ThefournucleotidesareshowninFigure1-4aandb.Thecarbonsinthedeoxyribosesugargroupareassignednumbersfollowedbyaprime(1′,2′,andsoforth)todistinguishthemfromthenumberingoftheatomsinthebases.InDNA,thenucleotidesareconnectedtoeachotheratthe3′and5′positions,asshowninFigure1-4(c);henceeachchainissaidtohavepolarity,withoneendhavinga5′phosphategroupandtheothera3′OHgroup.Theconnectingbondsbetweentherepeatingsugarandphosphategroupsarecalledphosphodiesterbonds.
Thepolaritiesofthetwointertwinednucleotidechainsareinoppositedirections;thechainsaresaidtobeantiparallel.Thetwonucleotidechainsareheldtogetherbyweakbondscalledhydrogenbonds,betweenbases.Hydrogenbondingisveryspecificbecauseofa“lock-and-key”fitbetweentheshapeandatomicchargeofthebases.Adeninepairsonlywiththymine,andguaninepairsonlywithcytosine.Thebasesthatformbasepairsaresaidtobecomplementary.HenceashortsegmentofDNAdrawnwitharbitrarynucleotidesequencemightbe
ThesamestructureisdepictedinmoredetailinFigure1-5.Althoughhydrogenbondsareweakindividually,theircombinedbondingholdsthetwochainstogetherinastablemanner.Furthermore,itisimportantthatthebondsbetweenthebasesberelativelyweakbecause,asweshallsee,thetwochainshavetobepulledaparttoallowthereplicationprocesstowork.Thebasepairs,whichrundownthecenterofthedoublehelix,areflathydrophobicstructuresthathaveatendencytostackowingtotheexclusionofwatermolecules.ThisstackingdrawsthetwointertwinedstrandsofDNAintoitshelicalstructure(Figure1-6).
Forreplicationtotakeplace,thetwostrandsofthedoublehelixmustunwindinonedirection,ratherliketheopeningofazipper.Thetwoexposednucleotidechainsthenactasalignmentguides,ortemplates,forthedepositionoffreenucleotides.Thesenucleotideshavebeensynthesizedinsidethecellanda