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Lecture3
Gene+cs
BIOL335
Pleasesignana*endancesheet
Classstartsat4pmsharp!
WeeklyScienceWri9ng
Onepagehandwri(ensummaryanddiscussion(cool?
bogus?why?)ofalaypressscien9ficar9clepublishedin2016
DueeveryMondaystar9ngSept19th(nextMonday)
-checkedforcomple+on,spot-checkedforaccuracy
-includesource9tle,author,nameofwebsite,publica9ondate
Iwillconsideronly"legit"highqualityar9clespublishedby:
NYTimes,WallStJournal,TheAtlan9c,WashingtonPost,NPR/WNYC,
TheGuardian,BBC,Scien9ficAmerican,Slate,Wired,Cell,Nature,
TechnologyReview,Discover,Na9onalGeographic,Science,Vox,
TheEconomist,CurrentBiology,TheNewYorker,FiveThirtyEight
Mosttopicsfine,exceptforar9clesprimarilydealingwithbusiness
aspects,orar9clesaboutnutri9on(baconcuresbaldness,etc,since
mostofthesestudiesareunderpowered)
-Abitofhistory
-Physicalstructureofchromosomes
-Mitosis–soma9ccelldivision
-Meiosis–gamete/germcellproduc9on
-Whysexisimportant
Inthemid-late1800's,whileMendel
wasbeingforgo*en...
Peoplewereusingnewlydevelopedstainsto
visualizepreviouslyinvisiblemicroscopicobjects
Onionskinviewedwith
brigheieldlightmicroscope
WaltherFlemming,1879
Lookedatlivesalamander
tailfincells
Flemmingstainedcellswith
adyeandfoundthat
somethinginsidethe
nucleusstainedvigorously.
aprocesswiththreads=mitosis
Hecalledit“chroma5n”
(“stainablematerial”).
Discovered“Mitosis”–
"aprocesswiththreads"
WenowcallFlemming’s
“threads” “chromosomes.”
5
TheodorBoveri(1895)andE.B.Wilson(1896)
removednucleifromseaurchineggsand
replacedthemwithtransplantednuclei
Nevergrewtoadulthoodbutsome9meseggswith
transplantednucleiwereabletohatchintolarvae!
–Suggeststhatsomethinginthenuclei(chromosomes)are
requiredforcrea9nganorganism
6
WalterSu*on(1903)
-AKansasfarmboy,playedbasketballatUKansas,
coachedbyJamesNaismith(inventedthegame)
-Performedhispioneeringcytologystudieson
grasshopper9ssuesasanengineering
-
undergradandmastersstudentat
UKansasandColumbia
-Publishedtwoclassicpapers,butnevercompleted
histhesis!(droppedouttoworkonanoilfield)
-Laterbecameasurgeon,andpioneeredappendectomies
andtheuseofthethennew"X-rays"toguidesurgeries
-Diedatage39,ironically,fromappendici9s
ChromosomesinSexualReproduc9on
germcellsaka
gametes
(sperm&egg)
producedby
meiosis
Fer5liza5on:fusionof
gametestoformzygote
Zygotewith46
chromosomes
Eggwith23
chromosomes
Halfthenumber
ofchromosomes
(haploid)
Spermwith23
chromosomes
Zygotehasfullcomplement
ofchromosomes(diploid)
Producessoma5ccellsby
mitosistodevelopintoadult
Key
Haploid (n)
Diploid (2n)
Haploid gametes (n = 23)
Egg (n)
Sperm (n)
MEIOSIS
Ovary
FERTILIZATION
Testis
Diploid
zygote
(2n = 46)
Mitosis and
development
Multicellular diploid
adults (2n = 46)
Su*on'smicroscopyofrealchromosomes
Mendel'sabstractgenes
1.Discoveredthatchromosomescomeinpairs.
a.Anindividualhastwoallelesforeachgene.
2.Viameiosis,eachgametegetsasinglemember
ofachromosomepair.
b.Allelesareseparatedduringgameteforma:on.
3.Surmisedthatduringfer9liza9on,theeggand
spermeachcontributeamemberofachromosome
pair,regenera9ngthefullnumberofchromosomes.
c.Anindividualgetsoneallelefromeachparent.
Homologous
chromosomes,
onefromeach
parent
Thegene9cmaterial(DNA)ofanorganismis
splitupintomul9plechromosomepairs
Dad
Mom
Thenumberofchromosomesinagenome
variesconsiderably,evenamongrelatedspecies
Eukaryo9cChromosomes/CellDivision
•  Eukaryo9ccelldivisionconsistsof:
–  Mitosis,divisionofthegene9cmaterialinnucleus
–  Cytokinesis,divisionofthecytoplasm
•  Developmentfromafer9lizedegg-cyclesofmitosis
andcytokinesistoproduceafullydeveloped
mul9cellularhumanmadeupof200trillioncells
•  Meiosis–produc9onofgametesorgermcells
(spermandegg)
Duringcelldivision,chromosomescondenseto
formthestructuresseenbyFlemming
Onioncellsatvariousstatesofcelldivision
KaryotypewithGiemsastainingduringmitosis
canbeusedtoiden9fychromosomes
Eachchromosomehasacharacteris9cbandingpa*ern
Chromosomes,chroma:ds,centromere
Iden+cal
Sister
chroma+ds
Centromere
0.5µm
•  Beforecelldivision,DNAisreplicated&chromosomes
condense
•  Eachduplicatedchromosomehasiden9cal2sister
chroma5ds(joinedcopiesoftheoriginalchromosome),which
separateduringcelldivision
•  Centromere-narrow waist ofduplicatedchromosome,
wherethe2chroma9dsaremostcloselya*ached
Centromerejoining
iden9calduplicated
sisterchroma9ds
Chromosomescanbeiden9fiedbythe
loca9onofthecentromerethatjoinsiden9cal
sisterchroma9ds
Insidethecell,DNAispackagedintochromosomes
Bacterialchromosomes
Bacterialchromosomeisadouble-stranded,circularDNA
moleculeassociatedwithasmallamountofprotein
TheDNAis
supercoiled andfoundinaregionofthecell
calledthenucleoid
Ecolicellsurrounded
byitsun-compactedDNA
BinaryFission
ofbacteria
1 Chromosome
replica+on
begins.
2 Replica+on
con+nues.
3 Replica+on
finishes.
4 Twodaughter
cellsresult.
Originof
replica+on
E.colicell
Cellwall
Plasmamembrane
Bacterialchromosome
Twocopies
oforigin
Origin
Origin
twodaughter
chromosomes
ac9velymoveapart
Chromosomeultrastructure
Eukaryo9cchromosomeshavelinearDNAmolecules
associatedwithalargeamountofprotein
Chroma5n,acomplexofDNAandprotein,isfoundin
thenucleusofeukaryo9ccells
Chromosomesfitintothenucleusthroughan
elaborate,mul9levelsystemofpacking
Eukaryotechromosomesarea
nucleoproteincomplex
-146bpofDNAwrappedaround
histoneproteinoctamers(8subunits)
-Wrappingandunwrappingishighlyregulated
-Spacingbetweenbeadsisalsohighlyregulated
Duringcelldivision,chroma9ncondensesto
formthestructuresseenbyFlemming
(interphase,noteasilyvisible)
(mitosis,easilyvisible)
Summaryof
celldivision
Chromosomal
DNAmolecules
Chromosomes
1
Centromere
Chromosome
arm
Chromosomeduplica+on
(includingDNAreplica+on)
andcondensa+on
ReplicateDNA
2
Sister
chroma+ds
Giveeachnew
cellacopy
Separa+onofsister
chroma+dsinto
twochromosomes
3
CellCycle
•  Thecellcycleconsistsof:
–  Mito+c(M)phase(mitosisandcytokinesis)
–  Interphase(cellgrowthandcopyingofchromosomes
inprepara9onforcelldivision)
•  Interphase(about90%ofthecellcycle)canbe
dividedintosubphases –  G1phase( firstgap )
–  Sphase( synthesis )
–  G2phase( secondgap )
•  Thecellgrowsduringallthreephases,but
chromosomesareduplicatedonlyduringSphase
CellCycle
INTERPHASE
G1
S
(DNAsynthesis)
G2
MIT
(M) OTIC
PHA
SE
T ERPHASE
IN
CellCycle
Cytokinesis
Mitosis
G1
S
G2
MITOTIC(M)PHASE
Prophase
Telophaseand
Cytokinesis
Prometaphase
Anaphase
Metaphase
10µm
Mitosisisconven9onallydividedintofivephases
–  Prophase–chromosomesstar9ngtocondense,spindleforming
–  Prometaphase–chromosomescondensed,nuclearenvelope
breakdown
–  Metaphase–chromosomesmeetatthemiddle
–  Anaphase–chromosomesmoveapart
–  Telophase–cellsstartdividing;cytokinesis
Cytokinesisoverlapsthela*erstagesofmitosis
G2ofInterphase
Centrosomes
(withcentriolepairs)
Nucleolus
Nuclear
envelope
Chroma+n
(duplicated)
Plasma
membrane
Prophase
Earlymito+c
spindle
Aster
Prometaphase
Centromere
Chromosome,consis+ng
oftwosisterchroma+ds
Fragments
ofnuclear
envelope
Kinetochore
Metaphase
Nonkinetochore
microtubules
Kinetochore
microtubule
Anaphase
Metaphase
plate
Spindle
Centrosomeat
onespindlepole
TelophaseandCytokinesis
Cleavage
furrow
Daughter
chromosomes
Nuclear
envelope
forming
Nucleolus
forming
G2 of Interphase
Centrosomes
(with centriole
pairs)
Chromatin
(duplicated)
Prophase
Early mitotic
spindle
Plasma
membrane
Nucleolus
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
10 µm
Nuclear
envelope
Aster
Centromere
Prometaphase
G2 of Interphase
Prophase
Prometaphase
Metaphase
Anaphase
Metaphase
plate
Centrosome at
one spindle pole
Cleavage
furrow
Daughter
chromosomes
Nucleolus
forming
Nuclear
envelope
forming
10 µm
Spindle
Telophase and Cytokinesis
Metaphase
Anaphase
Telophase and Cytokinesis
MitosisinPlant(onion)cells
Chromosomeultrastructure
"Chromosome
pain9ng"tolabel
eachchromosome
Thoughinterphase
chromosomesarenot
condensed,theys9ll
occupyspecificrestricted
regionsinthenucleus
Interphase
Meiosis–
produc9onof
gametes
(sperm&egg)
red=maternalchromosome
blue=paternalchromosome
Pair of homologous
chromosomes in
diploid parent cell
Duplicated pair
of homologous
chromosomes
Sister
chromatids
Chromosomes
duplicate
Diploid cell with
duplicated
chromosomes
Meiosis I
1 Homologous
chromosomes separate
Haploid cells with
duplicated chromosomes
Meiosis II
2 Sister chromatids
separate
Haploid cells with unduplicated chromosomes
Meiosis–produc9onofgametes(sperm&egg)
•  Likemitosis,meiosisisprecededbythereplica9onof
chromosomes(SPhase–ONLYoccurs1:me)
•  Meiosistakesplacein2setsofcelldivisions,called
–  meiosisI(separa+onofhomologouschromosomes)
–  meiosisII(separa+onofsisterchroma+ds)
•  The2celldivisionsresultin4daughtercells,ratherthan
the2daughtercellsinmitosis
•  Eachdaughtercellhasonlyhalfasmanychromosomesas
theparentcell
TheVarietyofSexualLifeCycles
•  Thealterna9onofmeiosis&fer9liza9onis
commontoallorganismsthatreproducesexually
•  The3maintypesofsexuallifecyclesdifferinthe
9mingofmeiosis&fer9liza9on
Key
Haploid(n)
n
Gametes
n
Mitosis
n
MEIOSIS
n
FERTILIZATION
n
Diploid
mul+cellular
organism
(a)Animals
Zygote
2n
Mitosis
Diploid
mul+cellular
organism
(sporophyte)
Mitosis
n
n
Spores
Gametes
MEIOSIS
2n
Haploidunicellularor
mul+cellularorganism
Haploidmul+-
cellularorganism
(gametophyte)
Diploid(2n)
2n
Mitosis
n
n
n
n
n
Gametes
FERTILIZATION
FERTILIZATION
MEIOSIS
2n Zygote
Mitosis
(b)Plantsandsomealgae
Mitosis
2n
Zygote
(c)Mostfungiandsomepro+sts
n
Gametesaretheonly
Haploid (n)
haploidcellsin
Diploid (2n)
animals.
Gametes n
n
Producedbymeiosis
n
&undergonofurther
celldivisionsbefore
MEIOSIS
FERTILIZATION
fer9liza9on.
Zygote 2n
Gametesfusetoform
2n
adiploidzygotethat Diploid
Mitosis
dividesbymitosisto multicellular
organism
developintoa
mul9cellularorganism
Plants&somealgaeexhibitan
alterna+onofgenera+ons
Haploid(n)
Diploid(2n)
Lifecycleincludesbothdiploid&
Haploidmul+-
cellularorganism
haploidmul9cellularstages
(gametophyte)
Diploidorganism=sporophyte,
Mitosis
Mitosis
n
n makeshaploidsporesbymeiosis
n
n
n
Spores
Gametes
FERTILIZATION Eachsporegrowsbymitosisinto
MEIOSIS
ahaploidgametophyte
Agametophytemakes
2n
2n
Diploid
Zygote
haploidgametesbymitosis!!
mul+cellular
Mitosis
organism
(verydifferentfromanimals!)
(sporophyte)
Fer9liza9onofgametesresultsin
adiploidsporophyte
Haploid (n)
Diploid (2n)
Haploid unicellular or
multicellular organism
Mitosis
n
n
n
Mitosis
n
Gametes
MEIOSIS
n
FERTILIZATION
2n
Zygote
Inmostfungiandsomepro9sts,
theonlydiploidstageisthe
single-celledzygote;thereisno
mul9cellulardiploidstage
Zygoteproduceshaploidcells
bymeiosis
Eachhaploidcellgrowsby
mitosisintoahaploid
mul9cellularorganism
Haploidadultproducesgametes
bymitosis
Yeastlifecycle
ma9ngshmoos
ofoppositema9ng
typesfuseto
formdiploid
haploid
budding
diploid
budding
haploids
from
meiosis
TheVarietyofSexualLifeCycles
•  Dependingonthetypeoflifecycle,either
haploidordiploidcellscandividebymitosis
•  However,onlydiploidcellscanundergomeiosis
–whynothaploidcells?
•  Althoughthethreetypesofsexuallifecycles
differinthe9mingofmeiosisandfer9liza9on,
theyshareafundamentalresult:gene9c
varia9onamongoffspring(thereasonforsex)
MEIOSISI:Separateshomologouschromosomes
Prophase I
Centrosome
(with centriole pair)
Sister
chromatids
Chiasmata
Spindle
Telophase I and
Cytokinesis
Anaphase I
Metaphase I
Sister chromatids
remain attached
Centromere
(with kinetochore)
Metaphase
plate
Fragments
Homologous
chromosomes of nuclear
envelope
Homologous
chromosomes
separate
Microtubule
attached to
kinetochore
Cleavage
furrow
Each pair of homologous
chromosomes separates.
Chromosomes line up
Duplicated homologous
chromosomes (red and blue) by homologous pairs.
pair and exchange segments;
2n = 6 in this example.
Two haploid
cells form; each
chromosome
still consists
of two sister
chromatids.
Homologouschromosomescross-over
inProphaseI
Typicallyoccupies>90%of9me
requiredformeiosis
Synapsis-homologous
chromosomeslooselypairup,
F
alignedgenebygene
H
Crossingover-nonsister
chroma9dsexchangeDNA
segments
Eachpairofchromosomesforms
atetrad,agroupof4chroma9ds
–  Eachtetradusuallyhas1or
morechiasmata,X-shaped
Humaneggsremaininthisstageun:l
regionswherecrossingover
puberty,wheneachmonthoneegg
occurred
completesmeiosisIandisovulated.
Chiasmata–crossingover
twocopiesofthechromosomefromMom
twocopiesofthechromosomefromDad
crossingover:MomandDad
getscrambled
Recombina5onscramblesthealleleson
homologouschromosomesfromMomandDad,
resul9nginnewcombina9onsofalleles
Crossingover(recombina5on)isthereciprocal
exchangeofchromosomesegmentsat
correspondingsegmentsofthehomologous
chromosomes.
Crossingoveryieldsarecombinantchromosome.
Crossingovergeneratesdiversity
Atthemolecularlevel,
sec9onsofDNAstrands
arebeingswapped
betweenhomologous
chromosomesduring
prophaseIofmeiosis
DNAdouble-strand
break
Endschewedback
tocreatesinglestrandeds9ckyends
S9cky-endsinvade
intacthomologous
chromosome,
formingHoliday
junc5ons
DNAreplica9on
primedfrom
invading
s9cky-ends
Holidayjunc9ons
resolvedbybreaking
invadingstrandsandliga9ng
newlyreplicatedstrands
MEIOSISII:Separateschroma+ds
ProphaseII
MetaphaseII
AnaphaseII
TelophaseIIand
Cytokinesis
Duringanotherroundofcelldivision,thesisterchroma+dsfinallyseparate;
fourhaploiddaughtercellsresult,containingunduplicatedchromosomes.
Sisterchroma+ds
separate
Haploiddaughter
cellsforming
ProphaseII
•  UnlikeProphaseIorinmitosis,
NODNAreplica5on!!!
•  Spindleapparatusforms
•  Chromosomes(eachs9ll
composedof2chroma9ds)
movetowardmetaphaseplate
MetaphaseII
•  Sisterchroma9dsarearrangedat
metaphaseplate
•  Becauseofcrossingoverinmeiosis
I,the2sisterchroma9dsofeach
chromosomearenolonger
gene+callyiden+cal
•  Kinetochoresofsisterchroma9ds
a*achtomicrotubulesextending
fromoppositepoles
AnaphaseII
•  Sisterchroma9dsseparate
•  Sisterchroma9dsofeach
chromosomenowmoveas2
newlyindividualchromosomes
towardoppositepoles
TelophaseII&Cytokinesis
•  Chromosomesarriveatopposite
poles
•  Nucleiform&chromosomesbegin
decondensing
•  Cytokinesisseparatesthecytoplasm
•  Attheendofmeiosis:4daughter
cells,eachwithahaploidsetof
unreplicatedchromosomes
•  Eachdaughtercellisgene5cally
dis5nctfromtheothers&fromthe
parentcell
ComparisonofMitosisandMeiosis
•  Threeeventsareuniquetomeiosis,&allthree
occurinMeiosisl
–  Synapsis&crossingoverinprophaseI:Homologous
chromosomesphysicallyconnect&exchangegene5c
informa5on
–  Atthemetaphaseplate,therearepairedhomologous
chromosomes(tetrads),insteadofindividual
replicatedchromosomes
–  AtanaphaseI,itishomologouschromosomes,instead
ofsisterchroma9ds,thatseparate
Gene9cVaria9onandEvolu9on
Muta9ons
–  changesinanorganism sDNA
–  theoriginalsourceofgene9cdiversity
–  createdifferentversionsofgenes=alleles
Reshufflingofallelesduringsexualreproduc9on
producesgene5cvaria5on
Gene9cVaria9onandEvolu9on
Thebehaviorofchromosomesduringmeiosis&
fer9liza9onisresponsibleformostofthevaria9on
thatarisesineachgenera9on
Threemechanismscontributetogene9cvaria9on:
–  Independentassortmentofchromosomes
–  Randomfer9liza9on
–  Crossingover
IndependentAssortmentofChromosomes
Homologouspairsofchromosomesorientrandomlyat
metaphaseIofmeiosis
Inindependentassortment,eachpairofchromosomessorts
maternal&paternalhomologsintodaughtercells
independentlyoftheotherpairs
Thenumberofcombina9onspossiblewhenchromosomes
assortindependentlyintogametesis2n,wherenisthe
haploidnumber
Forhumans(n=23),thereare8.4million(223)possible
combina9onsofchromosomes
IndependentAssortmentof
Chromosomes
Possibility2
Possibility1
Twoequallyprobable
arrangementsof
chromosomesat
metaphaseI
MetaphaseII
Daughter
cells
Combina+on1
Combina+on2
Combina+on3
Combina+on4
RandomFer9liza9on
•  Randomfer+liza+onaddstogene9cvaria9on
becauseanyspermcanfusewithanyovum
(unfer9lizedegg)
•  Thefusionof2gametes(eachwith8.4million
possiblechromosomecombina9onsfrom
independentassortment)producesazygotewith
anyofabout70trilliondiploidcombina9ons
Crossing-overgeneratesevenmore
gene9cdiversity
•  Crossing-overproducesrecombinant
chromosomes,whichcombineDNAinheritedfrom
eachparent
•  Crossingovercontributestogene9cvaria9onby
combiningDNAfrom2parentsintoasingle
chromosome
•  Virtuallyguaranteeseachzygoteisunique
(unlessdealingwithclonal/inbredpopula9on)
Crossing-over
generateseven
moregene9c
diversity
ProphaseI
ofmeiosis
Pairofhomologs
Nonsisterchroma+ds
heldtogether
duringsynapsis
Chiasma
Centromere
AnaphaseI
AnaphaseII
Daughter
cells
Recombinantchromosomes
Evolu9onarySignificanceof
Gene9cVaria9on
Naturalselec9onresultsintheaccumula9onof
gene9cvaria9ons(adapta5on)favoredbythe
environment
Sexualreproduc9oncontributestothegene9c
varia5oninapopula9on,whichoriginatesfrom
muta9ons
Whysex(fromateleologicalperspec9ve)?
"Sex:thepleasureismomentary,theposi9on
ridiculous,andtheexpensedamnable."
- PhilipDormerStanhope,
4thEarlofChesterfield(1694-1773)
"...whynewbeingsshouldbeproducedbythe
unionofthetwosexualelements,insteadofbya
processofparthenogenesis...Thewholesubject
isasyethiddenindarkness."
-Darwin1862
TheRedQueenHypothesis
Sexisneededfortheunendingwarbetween
hostandparasite?
"Well,inourcountry,"saidAlice,s9llpan9ngali*le,"you'd
generallygettosomewhereelse—ifyouranveryfastfora
long9me,aswe'vebeendoing.”
"Aslowsortofcountry!"saidtheQueen."Now,here,yousee,
ittakesalltherunningyoucan
do,tokeepinthesameplace.
Ifyouwanttogetsomewhere
else,youmustrunatleast
twiceasfastasthat!"
-ThroughtheLooking-Glass,
andWhatAliceFoundThere
TheRedQueenHypothesisandSex
• Incontrolledexperiments,sexualpopula9onsare
be*erabletoavoidex5nc5onfromco-evolving
parasitesthanasexualpopula9ons
• Ma9ngpreferencesinrodents(andperhapsevenus!)
maybelinkedtoMHCgenesinvolvedinimmune
responses
Next9me:
Uni9nggene9csandchromosomemicroscopy:
T.H.Morgan,Drosophila,and
theFlyRoomBoys