overview: locating genes along chromosomes mendel’s “hereditary factors” were genes today we...

Overview: Locating Genes Along Overview: Locating Genes Along ChromosomesChromosomes

Mendel’s “hereditary factors” were genes

Today we can show that genes are located on chromosomes

The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

Figure 15.1Figure 15.1

CONCEPT 15.1: MENDELIAN CONCEPT 15.1: MENDELIAN

INHERITANCE HAS ITS PHYSICAL INHERITANCE HAS ITS PHYSICAL

BASIS IN THE BEHAVIOR OF BASIS IN THE BEHAVIOR OF

CHROMOSOMESCHROMOSOMES

Mendel and MeiosisMendel and MeiosisP Generation

F1 Generation

Yellow-roundseeds (YYRR)

Green-wrinkledseeds (yyrr)

Meiosis

Fertilization

Gametes

Y

YR R

YR

y

yr

y r

All F1 plants produceyellow-round seeds (YyRr).

Meiosis

Metaphase I

Anaphase I

Metaphase II

R R

R R

R R

R R

R R R R

r r

r r

r r

r r

r r r r

Y Y

Y Y

Y Y

Y Y

Y Y Y Y

y y

y y

y y

y y

yy y y

Gametes

LAW OF SEGREGATIONThe two alleles for eachgene separate duringgamete formation.

LAW OF INDEPENDENTASSORTMENT Alleles of geneson nonhomologous chromosomesassort independently duringgamete formation.

1

2 2

1

1/41/4

1/41/4YR yr Yr yR

F2 Generation

3 3Fertilization recombinesthe R and r alleles at random.

Fertilization results in the 9:3:3:1 phenotypic ratioin the F2 generation.

An F1 F1 cross-fertilization

9 : 3 : 3 : 1

r

P Generation Yellow-roundseeds (YYRR)

Green-wrinkledseeds (yyrr)

Meiosis

Fertilization

Gametes

Y

YR R

YR

y

yr

y r

r

Mendel and MeiosisMendel and Meiosis

Figure 15.2bFigure 15.2b

F1 Generation

All F1 plants produceyellow-round seeds (YyRr).

Meiosis

Metaphase I

Anaphase I

Metaphase II

R R

R R

R R

R R

R R R R

r r

r r

r r

r r

r r r r

Y Y

Y Y

Y Y

Y Y

Y Y Y Y

y y

y y

y y

y y

yy y y

Gametes

LAW OF SEGREGATIONThe two alleles for eachgene separate duringgamete formation.

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

1

2 2

1

1/41/4

1/41/4YR yr Yr yR

F2 Generation

3Fertilization recombines the R and r alleles at random.

Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation.

An F1 F1 cross-fertilization

9 : 3 : 3 : 1

LAW OF SEGREGATION LAW OF INDEPENDENTASSORTMENT

3

Mendel and MeiosisMendel and Meiosis

MorganMorgan’’s Experimental Evidence for s Experimental Evidence for MendelMendel

The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist

Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors

MorganMorgan’’s Choice of Experimental s Choice of Experimental OrganismOrganism

Several characteristics make fruit flies a convenient organism for genetic studies

◦ They produce many offspring ◦ A generation can be bred every two weeks◦ They have only four pairs of chromosomes

Morgan noted wild type, or normal, phenotypes that were common in the fly populations

Traits alternative to the wild type are called mutant phenotypes


All offspringhad red eyes.

PGeneration

F1

Generation

F2

Generation

F2

Generation

F1

Generation

PGeneration

Eggs

Eggs

Sperm

Sperm

XX

XY

w

w

ww w

w

ww w

w

w

w

w

w

ww w

RESULTS

EXPERIMENT

CONCLUSION

The F1 generation all had red eyes

The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes

Morgan determined that the white-eyed mutant allele must be located on the X chromosome

All offspringhad red eyes.

PGeneration

F1

Generation

F2

Generation

RESULTS

EXPERIMENT

F2

Generation

PGeneration

Eggs

Eggs

Sperm

Sperm

Xw

CONCLUSION

XX Y

w

ww w

w

ww w

w

w

w

w

w

ww w

F1

Generation

CONCEPT 15.2: SEX-CONCEPT 15.2: SEX-LINKED GENES EXHIBIT LINKED GENES EXHIBIT UNIQUE PATTERNS OF UNIQUE PATTERNS OF INHERITANCEINHERITANCE

In humans and some other animals, there is a chromosomal basis of sex determination

The Chromosomal Basis of SexThe Chromosomal Basis of Sex

Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome

The SRY gene on the Y codes for a protein that directs the development of male anatomical features

X

Y

Sex Sex Determination Determination

SystemsSystems

Parents

orSperm

or

Egg

Zygotes (offspring)

44 XY

44 XX

22 X

22 Y

22 X

44 XX

44 XY

22 XX

22 X

76 ZW

76 ZZ

32 (Diploid)

16 (Haploid)

(a) The X-Y system

(b) The X-0 system

(c) The Z-W system

(d) The haplo-diploid system

Human males are XYHuman females are XX

Other organisms use different systems!

Figure 15.6aFigure 15.6a

Parents

or

Sperm

or

Egg

Zygotes (offspring)

44 XY

44 XX

22 X

22 Y

22 X

44 XX

44 XY

22 XX

22 X

(a) The X-Y system

(b) The X-0 system

Figure 15.6bFigure 15.6b

76 ZW

76 ZZ

32 (Diploid)

16 (Haploid)

(c) The Z-W system

(d) The haplo-diploid system

Sex-LinkageSex-Linkage

A gene that is located on either sex chromosome is called a sex-linked gene

Genes on the Y = Y-linked genes; there are few of these

Genes on the X = X-linked genes

X-linked InheritanceX-linked InheritanceX chromosomes code for many genes not related to sex

Some disorders caused by recessive alleles on the X chromosome in humans

◦ Color blindness (mostly X-linked)◦ Duchenne muscular dystrophy◦ Hemophilia

Transmitting X-linked genes: ColorblindnessTransmitting X-linked genes: Colorblindness

Eggs Eggs Eggs

Sperm Sperm Sperm

(a) (b) (c)

XNXN XnY XNXn XNY XNXn XnY

Xn Y XN Y YXn

Xn Xn

XN

XN

XN XNXNXn XNY

XNY

XNY XNY

XnY XnYXNXn XNXn

XNXnXNXN

XnXn

X-linked recessive disorders are much more common in males than in females

For a recessive X-linked trait to be expressed◦ A female needs two copies of the allele (homozygous)◦ A male needs only one copy of the allele (hemizygous)

X Inactivation in Female X Inactivation in Female MammalsMammalsIn mammalian females, one

of the two X chromosomes in each cell is randomly inactivated during embryonic development

The inactive X condenses into a Barr body

If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

Early embryo:

X chromosomesAllele fororange fur

Allele forblack fur

Two cellpopulationsin adult cat:

Cell division andX chromosomeinactivation

Active XInactive X

Active X

Black fur Orange fur

Female Mosaics: Female Mosaics: X InactivationX Inactivation

CONCEPT 15.3: LINKED CONCEPT 15.3: LINKED GENES TEND TO BE GENES TEND TO BE INHERITED TOGETHER INHERITED TOGETHER BECAUSE OF LOCATIONBECAUSE OF LOCATION

Each chromosome has hundreds or thousands of genes (except the Y chromosome)Genes located on the same chromosome that tend to be inherited together are called linked genes

Gene LinkageGene Linkage

Linked genes assort together

How Linkage Affects InheritanceHow Linkage Affects InheritanceMorgan did other experiments with

fruit flies to see how linkage affects inheritance of two characters

Morgan crossed flies that differed in traits of body color and wing size

Wild type(gray body, normal wings)

Double mutant(black body,vestigial wings)

Figure 15.9-1Figure 15.9-1P Generation (homozygous)


b b vg vg b b vg vg


EXPERIMENT



F1 dihybrid(wild type)

TESTCROSS

b b vg vg

b b vg vg

b b vg vg

b b vg vg


Double mutant

EXPERIMENT




Testcrossoffspring

TESTCROSS

b b vg vg

b b vg vg

b b vg vg

b b vg vg


Double mutant

Eggs

Sperm

EXPERIMENT

Wild type(gray-normal)

Black-vestigial

Gray-vestigial

Black-normal

b vg b vg b vg b vg

b b vg vg b b vg vg b b vg vg b b vg vg

b vg




Testcrossoffspring

TESTCROSS

b b vg vg

b b vg vg

b b vg vg

b b vg vg


Double mutant

Eggs

Sperm

EXPERIMENT

RESULTS

PREDICTED RATIOS

Wild type(gray-normal)

Black-vestigial

Gray-vestigial

Black-normal

b vg b vg b vg b vg

b b vg vg b b vg vg b b vg vg b b vg vg

965 944 206 185

1

1

1

1

1

0

1

0

If genes are located on different chromosomes:

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

:

:

:

:

:

:

:

:

:

b vg

Most offspring

F1 dihybrid femaleand homozygousrecessive malein testcross

or

b+ vg+

b vg

b+ vg+

b vg

b vg

b vg

b vg

b vg

Morgan found body color and wing size are usually inherited together in specific combinations (parental phenotypes)

However, nonparental phenotypes were also produced

Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent

Genetic Recombination and Genetic Recombination and LinkageLinkageOffspring with a phenotype matching one of the parental phenotypes are called parental types

Offspring with nonparental phenotypes are called recombinant types, or recombinants

A 50% frequency of recombination is observed for any two genes on different chromosomes

Parental vs. Recombinant PhenotypesParental vs. Recombinant Phenotypes

Gametes from green-wrinkled homozygousrecessive parent (yyrr)

Gametes from yellow-rounddihybrid parent (YyRr)

Recombinant offspring

Parental-type

offspring

YR yr Yr yR

yr

YyRr yyrr Yyrr yyRr

Recombination of Linked Genes: Recombination of Linked Genes: Crossing OverCrossing OverMorgan discovered that

genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed

Some process must occasionally break the physical connection between genes on the same chromosome

Crossing Over Crossing Over and and

RecombinationRecombination

Testcrossparents

Replicationof chromosomes

Gray body, normal wings(F1 dihybrid)

Black body, vestigial wings(double mutant)

Replicationof chromosomes

Meiosis I

Meiosis II

Meiosis I and II

Recombinantchromosomes

Eggs

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

b vg

bvg b vgb vg b vg

Testcrossoffspring

965Wild type

(gray-normal)

944Black-

vestigial

206Gray-

vestigial

185Black-normal

Sperm

Parental-type offspring Recombinant offspring

Recombinationfrequency

391 recombinants2,300 total offspring

100 17%

b vg b vgb vgb vg

b vg b vg b vg b vg

b vg

Recombinant chromosomes bring alleles together in new combinations in gametes

Genetic variation drives evolution!

Chromosome

Recombinationfrequencies

9% 9.5%

17%

b cn vg

Mapping Distance Between Genes Using Mapping Distance Between Genes Using Recombination DataRecombination Data

A linkage map is a genetic map of a chromosome based on recombination frequencies

The farther apart two genes are, the higher the probability crossover will occur and therefore the higher the recombination frequency

Distances between genes can be expressed as map units.

1 map unit = 1% recombination frequency

Genes that are far apart on the same chromosome can have a recombination frequency near 50%

Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes

Genetic Linkage Map: Cytogenic MappingGenetic Linkage Map: Cytogenic Mapping

Mutant phenotypes

Shortaristae

Blackbody

Cinnabareyes

Vestigialwings

Browneyes

Long aristae(appendageson head)

Gray body

Red eyes

Normalwings

Redeyes

Wild-type phenotypes

104.567.057.548.50

Concept 15.4: Alterations Concept 15.4: Alterations of chromosome number or of chromosome number or structure cause some structure cause some genetic disordersgenetic disorders

Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders

Plants tolerate such genetic changes better than animals do

Chromosomal Changes and Chromosomal Changes and DisordersDisorders

Meiosis I

Nondisjunction

Abnormal Abnormal Chromosome Chromosome NumberNumber

In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis

Meiosis I

Meiosis II

Nondisjunction

Non-disjunction


As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy

Meiosis I

Meiosis II

Nondisjunction

Non-disjunction

Gametes

Number of chromosomes

Nondisjunction of homo-logous chromosomes inmeiosis I

(a) Nondisjunction of sisterchromatids in meiosis II

(b)

n 1 n 1n 1 n 1 n 1n 1 n n


AneuploidyAneuploidy

The fertilization of gametes in which nondisjunction occurred

Offspring with this condition have an abnormal number of a particular chromosome

A monosomic zygote has only one copy of a particular chromosome

A trisomic zygote has three copies of a particular chromosome

Polyploidy: More than 2 Sets of Polyploidy: More than 2 Sets of ChromosomesChromosomes

◦ Triploidy (3n) is three sets of chromosomes◦ Tetraploidy (4n) is four sets of chromosomes

Polyploidy is common in plants, but not animals

Polyploids are more normal in appearance than aneuploids

Triploidy (3n) Hexaploidy (6n) Octoploidy (8n)

Alterations of Chromosome StructureAlterations of Chromosome Structure

Breakage of a chromosome can lead to four types of changes in chromosome structure

◦ Deletion removes a chromosomal segment

◦ Duplication repeats a segment◦ Inversion reverses orientation of a

segment within a chromosome◦ Translocation moves a segment from

one chromosome to another

(a) Deletion

(b) Duplication

A deletion removes a chromosomal segment.

A duplication repeats a segment.

BA C D E F G H

A B C D E F G H

A B C D E F G H B C

A B C E F G H


(c) Inversion

(d) Translocation

An inversion reverses a segment within a chromosome.

A translocation moves a segment from onechromosome to a nonhomologous chromosome.

A B C D E F G H

A D C B E F G H

A B C D E F G H M N O P Q R

GM N O C H FED A B P Q R


Human Disorders Due toHuman Disorders Due to Chromosomal Alterations Chromosomal Alterations

Most mammalian aneuploidy are lethal but some survive to birth and beyond

These surviving individuals have a set of symptoms, or syndrome.

Down Syndrome (Trisomy 21)Down Syndrome (Trisomy 21)Down syndrome is an aneuploid

condition that results from three copies of chromosome 21

It affects about 1in 700 children born in the US

The frequency of Down syndrome increases with the age of the mother

Aneuploidy of Sex ChromosomesAneuploidy of Sex ChromosomesSyndrome Genotype Occurrence Symptoms

Klinefelter Syndrome

XXY 1/500 ~ 1/1000 • Underdeveloped testes

• Male is sterile• Some secondary

female characteristics

XYY Syndrome XYY 1/1000 • Normal sexual development

• Taller than average

• Increased aggression

Turner Syndrome

(Monosomy X)

XO 1/2500 • Only viable monosomy in humans

• Sex organs do not develop; sterile

Trisomy X XXX 1/1000 • Learning disabled

• Fertile• Slightly taller

Turner’s Syndrome Klinefelter Syndrome

Disorders Caused by Disorders Caused by Structurally Altered ChromosomesStructurally Altered ChromosomesThe syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5

A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood

CML: Chronic CML: Chronic Myelogenous LeukemiaMyelogenous Leukemia Normal chromosome 9

Normal chromosome 22

Reciprocal translocation

Translocated chromosome 9

Translocated chromosome 22(Philadelphia chromosome)

CML caused by translocations of chromosomes

Concept 15.5: Some inheritance Concept 15.5: Some inheritance patterns are exceptions to standard patterns are exceptions to standard Mendelian inheritanceMendelian inheritance

There are two normal exceptions to Mendelian genetics

One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus

In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance

Genomic ImprintingGenomic Imprinting

For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits

Such variation in phenotype is called genomic imprinting

Genomic imprinting involves the silencing of certain genes that are “stamped” with an imprint during gamete production


(a) Homozygote

Paternalchromosome

Maternalchromosome

Normal Igf2 alleleis expressed.

Normal Igf2 alleleis not expressed.

Normal-sized mouse(wild type)

Mutant Igf2 alleleinherited from mother

Mutant Igf2 alleleinherited from father

Normal-sized mouse (wild type) Dwarf mouse (mutant)

Normal Igf2 alleleis expressed.

Mutant Igf2 alleleis expressed.

Mutant Igf2 alleleis not expressed.

Normal Igf2 alleleis not expressed.

(b) Heterozygotes

It appears that imprinting is the result of the methylation (addition of —CH3) of cysteine nucleotides

Genomic imprinting is thought to affect only a small fraction of mammalian genes

Most imprinted genes are critical for embryonic development

Inheritance of Organelle GenesInheritance of Organelle GenesExtranuclear genes (or cytoplasmic genes)

are found in organelles in the cytoplasmMitochondria, chloroplasts, and other plant

plastids carry small circular DNA moleculesExtranuclear genes are inherited

maternally because the zygote’s cytoplasm comes from the egg

The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems

◦ For example, mitochondrial myopathy and Leber’s hereditary optic neuropathy

Figure 15.UN03Figure 15.UN03

P generationgametes

Sperm Egg

This F1 cell has 2n 6 chromo-somes and is heterozygous for allsix genes shown (AaBbCcDdEeFf).Red maternal; blue paternal.

Each chromosome hashundreds or thousandsof genes. Four (A, B, C, F) are shown on this one.

The alleles of unlinkedgenes are either onseparate chromosomes(such as d and e)or so far apart on thesame chromosome(c and f) that theyassort independently.

Genes on the same chromo-some whose alleles are soclose together that they donot assort independently(such as a, b, and c) are saidto be genetically linked.

D

CBA

F

E d

cba

f

e

D

CB

A

F

e

d

E

f

c ba

overview: locating genes along chromosomes mendel’s “hereditary factors” were genes today we...

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