Post on 16-Dec-2015
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
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
Figure 15.4Figure 15.4
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
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
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)
Wild type(gray body, normal wings)
b b vg vg b b vg vg
Double mutant(black body,vestigial wings)
EXPERIMENT
Figure 15.9-2Figure 15.9-2P Generation (homozygous)
Wild type(gray body, normal wings)
F1 dihybrid(wild type)
TESTCROSS
b b vg vg
b b vg vg
b b vg vg
b b vg vg
Double mutant(black body,vestigial wings)
Double mutant
EXPERIMENT
Figure 15.9-3Figure 15.9-3P Generation (homozygous)
Wild type(gray body, normal wings)
F1 dihybrid(wild type)
Testcrossoffspring
TESTCROSS
b b vg vg
b b vg vg
b b vg vg
b b vg vg
Double mutant(black body,vestigial wings)
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
Figure 15.9-4Figure 15.9-4P Generation (homozygous)
Wild type(gray body, normal wings)
F1 dihybrid(wild type)
Testcrossoffspring
TESTCROSS
b b vg vg
b b vg vg
b b vg vg
b b vg vg
Double mutant(black body,vestigial wings)
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
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
Abnormal Abnormal Chromosome Chromosome NumberNumber
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
Abnormal Abnormal Chromosome Chromosome NumberNumber
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
Alterations of Chromosome StructureAlterations of Chromosome Structure
(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
Alterations of Chromosome StructureAlterations of Chromosome Structure
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
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
Figure 15.17Figure 15.17
(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