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TheChromosomalBasisofInheritanceBIOL100

Ch.8

Overview:Loca8ngGenesAlongChromosomes•  Mendel’s“hereditaryfactors”weregenes

•  Notknownatthe>me

•  Todaywecanshowthatgenesarelocatedonchromosomes

•  Loca>onofapar>culargene

•  Canbeseenbytaggingisolatedchromosomeswithafluorescentdyethathighlightsthegene

Fig.15-2

P Generation Yellow-round seeds (YYRR)

Y

F1 Generation

Y

R R

R Y

× r r

r

y

y

y

Meiosis

Fertilization Gametes

Green-wrinkled seeds ( yyrr)

All F1 plants produce yellow-round seeds (YyRr)

R R

Y Y r r

y y

Meiosis

R R

Y Y

r r

y y

Metaphase I

Y Y

R R r r

y yAnaphase I

r r

y Y

Metaphase II R

Y

R

y

yyy

R R

Y Y r r r r

yY Y R R

yRYryrYR1/4 1/4 1/4 1/4

F2 Generation

Gametes

An F1 × F1 cross-fertilization

9 : 3 : 3 : 1

LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation.

LAW OF SEGREGATION The two alleles for each gene separate during gamete formation.

1

2

3 3

2

1

2

•  Inmammals

•  twokindsofsexchromosomes-largerX,smallerYchromosome

•  RegionsonendsofYchromosomearehomologouswiththeXchromosome

•  TheSRYgeneontheYchromosomecodesforthedevelopmentoftestes

•  Someotheranimalshavedifferentmethodsofsexdetermina>on

•  Birds,fish,somecrustaceans,someinsects

•  Female:ZW;MaleZZ

Sex-linkedinheritance

InheritanceofSex-LinkedGenes•  Sexchromosomes

•  Havegenesformanycharactersunrelatedtosex

•  Sex-linkedgene

•  Agenelocatedoneithersexchromosome

•  Inhumans,sex-linkedusuallyreferstoageneonthelargerXchromosome

•  CalledX-linked

•  Sex-linkedgenesfollowspecificpaVernsofinheritance

•  Forarecessivesex-linkedtraittobeexpressed

•  Afemaleneedstwocopiesoftheallele

•  Amaleneedsonlyonecopyoftheallele

•  Sex-linkedrecessivedisorders

•  Aremuchmorecommoninmalesthaninfemales

Sex-linkedinheritance

(a) (b) (c)

XNXN XnY XNXn × × XNY XNXn × XnY

Y Xn Sperm Y XN Sperm Y Xn Sperm

XNXn Eggs XN

XN XNXn

XNY

XNY

Eggs XN

Xn

XNXN

XnXN

XNY

XnY

Eggs XN

Xn

XNXn

XnXn

XNY

XnY

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•  CommonX-linkedcondi>ons-Duetorecessivealleles

•  Colorblindness

•  Red/greenmostcommon

•  Mayinclude19chromosomesand56genes

•  Duchennemusculardystrophy

•  MutantDystrophingeneXp21

•  Hemophilia-Failedbloodclo]ng

•  Threetypes

•  TwofoundonXchromosome

Sex-linkedinheritance

XInac8va8oninFemaleMammals•  Mammalianfemales

•  OneofthetwoXchromosomesineachcellisrandomlyinac>vatedduringembryonicdevelopment

•  Barrbody

•  Thecondensedinac>veX

•  Ifafemaleisheterozygousforapar>culargenelocatedontheXchromosome

•  Shewillbeamosaicforthatcharacter

X chromosomes

Early embryo:

Allele for orange fur

Allele for black fur

Cell division and X chromosome inactivation Two cell

populations in adult cat:

Active X Active X

Inactive X

Black fur Orange fur

•  Eachchromosome

•  hashundredsorthousandsofgenes

•  linkedgenes

•  Geneslocatedonthesamechromosomethattendtobeinheritedtogetherarecalled

LinkedGenes

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HowLinkageAffectsInheritance•  ThomasHuntMorgandidexperimentswithfruitflies

•  Toseehowlinkageaffectsinheritanceoftwocharacters

•  Crossedflies

•  Thatdifferedintraitsofbodycolorandwingsize

b+ vg+

Parents in testcross

Most offspring

b+ vg+

b vg

b vg

b vg

b vg

b vg

b vg

×

or

Fig.15-9-4

EXPERIMENT P Generation (homozygous)

RESULTS

Wild type (gray body, normal wings)

Double mutant (black body, vestigial wings) ×

b b vg vg

b b vg vg

Double mutant TESTCROSS

×

b+ b+ vg+ vg+

F1 dihybrid (wild type)

b+ b vg+ vg

Testcross offspring Eggs b+ vg+ b vg b+ vg b vg+

Black- normal

Gray- vestigial

Black- vestigial

Wild type (gray-normal)

b vg

Sperm

b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg PREDICTED RATIOS

If genes are located on different chromosomes:

If genes are located on the same chromosome and parental alleles are always inherited together:

1

1

1

1

1 1

0 0

965 944 206 185

:

:

:

:

:

:

:

:

:

•  Morganfoundthat

•  Bodycolorandwingsize

•  Areusuallyinheritedtogetherinspecificcombina>ons

•  FailedLawofSegrega>on

•  Reasonedthattheywereonthesamechromosome

•  Thereforelinked

•  Theclosertogetheronchromosome

•  Morelikelytobeinheritedtogether

Linkedinheritance

RESULTS

Testcross offspring Eggs b+ vg+ b vg b+ vg b vg+

Black- normal

Gray- vestigial

Black- vestigial

Wild type (gray-normal)

b vg

Sperm

b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg

PREDICTED RATIOS If genes are located on different chromosomes:

If genes are located on the same chromosome and parental alleles are always inherited together:

1

1

1

1

1 1

0 0

965 944 206 185

:

:

:

:

:

:

:

:

:

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•  Afewnon-parentalphenotypeswerealsoproduced

•  Gene8crecombina8on

•  Theproduc>onofoffspringwithcombina>onsoftraits

•  Differingfromeitherparent

•  Ienotgray/normalorblack/ves>gial

•  Butgray/ves>gialorblack/normal

Linkedinheritance

RESULTS

Testcross offspring Eggs b+ vg+ b vg b+ vg b vg+

Black- normal

Gray- vestigial

Black- vestigial

Wild type (gray-normal)

b vg

Sperm

b+ b vg+ vg b b vg vg b+ b vg vg b b vg+ vg

PREDICTED RATIOS If genes are located on different chromosomes:

If genes are located on the same chromosome and parental alleles are always inherited together:

1

1

1

1

1 1

0 0

965 944 206 185

:

:

:

:

:

:

:

:

:

IndependentAssortmentofChromosomes•  Mendel-Combina>onsoftraitsinsomeoffspringdifferfromeitherparent

•  Parentaltypes

•  Offspringwithaphenotypematchingoneoftheparentalphenotypes

•  Recombinants

•  Offspringwithnonparentalphenotypes

•  newcombina>onsoftraits

•  A50%frequencyofrecombina>onobservedforanytwogenesondiffchromosomes

•  Dueen>relytoindependentassortmentinmetaphase1

YyRr

Gametes from green- wrinkled homozygous recessive parent ( yyrr)

Gametes from yellow-round heterozygous parent (YyRr)

Parental- type

offspring

Recombinant offspring

yr

yyrr Yyrr yyRr

YR yr Yr yR

Recombina8onofLinkedGenes:CrossingOver•  Morgandiscoveredthatgenescanbelinked

•  Butthelinkagewasincomplete

•  Evidentfromrecombinantphenotypes

•  Proposedthatsomeprocessmustsome>mesbreakthephysicalconnec>onbetweengenesonthesamechromosome

•  crossingoverofhomologouschromosomeswasthatmechanism

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MappingtheDistanceBetweenGenes•  AlfredSturtevant

•  StudentofMorgan

•  Constructedagene8cmap

•  anorderedlistofthegene>cloci

alongapar>cularchromosome

•  Predictedthat

•  Thefartheraparttwogenesare

•  thehighertheprobabilitythatacrossoverwilloccurbetweenthem

•  andthereforethehighertherecombina;onfrequency

Recombination frequencies

Chromosome 9% 9.5%

17%

b cn vg

•  Linkagemap

•  gene>cmapofachromosomebasedonrecombina>onfrequencies

•  Mapunits

•  Expressionofdistancesbetweengenes

•  onemapunit,orcen>morgan,representsa1%recombina>onfrequency

•  Mapunitsindicaterela>vedistanceandorder,notpreciseloca>onsofgenes

LinkageMap

Meiosis I

Nondisjunction

(a) Nondisjunction of homologous chromosomes in meiosis I

(b) Nondisjunction of sister chromatids in meiosis II

Meiosis II

Nondisjunction

Gametes

Number of chromosomes

n + 1 n + 1 n + 1 n – 1 n – 1 n – 1 n n

Altera8onsofchromosomenumberorstructure•  Large-scalechromosomalaltera>ons

•  Odenleadtospontaneousabor>ons(miscarriages)

•  Orcauseavarietyofdevelopmentaldisorders

•  Nondisjunc8on

•  Pairsofhomologouschromosomesorsisterchroma;dsdonotseparatenormallyduringmeiosis

•  Asaresultonegametereceivestwoofthesametypeofchromosome

•  Andanothergametereceivesnocopy

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•  Aneuploidy

•  Resultsfromthefer>liza>onofgametesinwhichnondisjunc>onoccurred

•  Offspringwiththiscondi>onhaveanabnormalnumberofapar>cularchromosome

AbnormalChromosomeNumber

•  Monosomiczygote

•  hasonlyonecopyofapar>cularchromosome

•  Trisomiczygote

•  hasthreecopiesofapar>cularchromosome

AbnormalChromosomeNumber

•  Polyploidy

•  condi>oninwhichanorganismhasmorethantwocompletesetsofchromosomes

•  Triploidy(3n)isthreesetsofchromosomes

•  Tetraploidy(4n)isfoursetsofchromosomes

•  commoninplants

•  butnotanimals

•  Polyploidsaremorenormalinappearancethananeuploids

ChromosomeNumber

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Altera8onsofChromosomeStructure•  Breakageofachromosomecanleadtofourtypesofchangesinchromosome

structure:

•  Dele8onremovesachromosomalsegment

•  Duplica8onrepeatsasegment

•  Inversionreversesasegmentwithinachromosome

•  Transloca8onmovesasegmentfromonechromosometoanother

Deletion A B C D E F G H A B C E F G H (a)

(b)

(c)

(d)

Duplication

Inversion

Reciprocal translocation

A B C D E F G H

A B C D E F G H

A B C D E F G H

A B C B C D E F G H

A D C B E F G H

M N O C D E F G H

M N O P Q R A B P Q R

AneuploidyDownSyndrome(Trisomy21)•  Downsyndrome

•  Aneuploidcondi>onthatresultsfromthreecopiesofchromosome21

•  Affectsaboutoneoutofevery700children

•  IntheUnitedStates

•  ThefrequencyofDownsyndromeincreaseswiththeageofthemother

•  Acorrela>onthathasnotbeenexplained

AneuploidyofSexChromosomes•  Nondisjunc>onofsexchromosomes

•  Producesavarietyofaneuploidcondi>ons

•  Klinefeltersyndrome

•  XXYmale

•  Sterile,smalltestes,somefemalesecondarysexualcharacteris>cs

•  MonosomyX,Turnersyndrome

•  X0female

•  sterile

•  itistheonlyknownviablemonosomyinhumans

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StructurallyAlteredChromosomes•  criduchat(“cryofthecat”)

•  specificdele>oninchromosome5

•  mentalretarda>on

•  catlikecry

•  usuallydieininfancyorearlychildhood

•  Transloca>onsofchromosomes

•  Certaincancers,includingchronic

myelogenousleukemia(CML)

Normal chromosome 9

Normal chromosome 22

Reciprocal translocation Translocated chromosome 9

Translocated chromosome 22 (Philadelphia chromosome)

InheritanceofOrganelleGenes•  Extranucleargenes(orcytoplasmicgenes)

•  genesfoundinorganellesinthecytoplasm

•  Mitochondria,chloroplasts,andotherplantplas>dscarrysmallcircularDNAmolecules

•  Extranucleargenes

•  inheritedmaternally

•  zygote’scytoplasmcomesfromtheegg

•  Thefirstevidenceofextranucleargenes

•  camefromstudiesontheinheritanceofyelloworwhitepatchesonleaves

•  Variega>on

•  Somedefectsinmitochondrialgenes

•  PreventcellsfrommakingenoughATP

•  Andresultindiseasesthataffectthemuscularandnervoussystems

•  Forexample,mitochondrialmyopathyandLeber’shereditaryop>cneuropathy

•  Failureofoxida>vephosphoryla>on

InheritanceofOrganelleGenes

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Youshouldnowbeableto:

1.  Explainthechromosomaltheoryofinheritanceanditsdiscovery

2.  Explainwhysex-linkeddiseasesaremorecommoninhumanmalesthanfemales

3.  Dis>nguishbetweensex-linkedgenesandlinkedgenes

4.  Explainhowmeiosisaccountsforrecombinantphenotypes

6.  Explainhownondisjunc>oncanleadtoaneuploidy

7.  Definetrisomy,triploidy,andpolyploidy

8.  Dis>nguishamongdele>ons,duplica>ons,inversions,andtransloca>ons

9.  ExplainwhyextranucleargenesarenotinheritedinaMendelianfashion