POST MENDELIAN GENETICS

1
POST MENDELIAN GENETICS
2
ANNOUNCEMENTS

• Genetics Problems (set 2) will be posted Fri.

3
OBJECTIVES

• Be familiar with contribution of early 20th
  century biologists to field of genetics
• Be able to predict patterns of inheritance for
  genes located on sex chromosomes
• Understand the concept of Linked Genes
• Understand how recombination of genes affect
  genetic variability
• Understand how frequency of recombination of
  linked genes is related to their distance from
  one another

4
THE CHROMOSOME THEORY OF INHERITANCE

• Walter Sutton Theodor Boveri (1903)
• Movement of chromosomes during meiosis provides
  the physical basis for Mendels principles

5
EXTENDING THE CHROMOSOME THEORY

• Thomas Hunt Morgan
• Drosophila melanogaster as a model species
• Small size
• Easy to culture
• Short reproductive cycle (10 days)
• Abundant progeny
• Developed external anatomy

6
MORGAN Drosophila

• Morgan Revealed
• Extensions of Mendels
• Rules
• Eye color linked to sex of progeny!

7
MORGANS WORK WITH Drosophila
Red Eyes In Flies Is Normal (wild)
White Eyes Is Rare (mutation)
Morgan discovered a white eyed male (mutant
phenotype)
8
MORGAN Drosophila

• To Explore How Eye Color is Inherited in Flies
  Morgan crossed

Red-eyed Female
White-eyed Male
X
Morgan concludes Red eye dominant to white eye
allele.
All F1 Have Red Eyes
9
MORGAN Drosophila

• Next, Morgan crossed F1

Red-eyed Female
Red-eyed Male
X
Only MALE Progeny Had WHITE EYES!!!
10
MORGAN Drosophila

• To test if sex and eye color were linked, Morgan
  crossed

Red-eyed Females (from F1)
X
White-eyed Males
Morgan concludes BOTH sexes can have WHITE eyes
Some F2 FEMALES had White eyes
11
MORGAN Drosophila

• However, Reciprocal Cross Produced Different
  Results!

White-eyed Females
X
Red-eyed Males (from F1)
All males had WHITE eyes (all females had red)
Morgan concludes EYE Color SEX are LINKED!!!
12
THE DISCOVERY OF SEX CHROMOSOMES

• Nettie Stevens
• Observed differences in chromosomes
• between male female beetles
• (Tenebrio molitor)
• Chromosomes named X and Y
• Half male gametes contain Y, other half X
• Male the heterogametic sex
• All female gametes contain X
• Female the homogametic sex

13
THE DISCOVERY OF SEX CHROMOSOMES

• Nettie Stevens
• Developed hypothesis about sex determination
• Male is formed when egg is fertilized by sperm
  carrying Y
• Female is formed when egg fuses with X carrying
  sperm

X
X
Y
14
NORMAL SEX CHROMOSOMES
A Male
15
BACK TO MORGAN

• Morgan guessed that
• D. melanogaster (like T.
• molitor) had chromosomes
• that differ between sexes
• Male flies carry X and Y chromosome (XY)
• Females carry 2 X (XX)

Gamete Formation In a Male Fly
sperm
sperm
16
MORGAN Drosophila

• The X Linked Hypothesis
• Morgan hypothesized that gene controlling eye
  color is located on X chromosome
• Females have 2 copies of gene for eye color
• Only homozygous recessive females exhibit white
  eyes
• Males have 1 copy (contributed by mom)
• Males with ONE ALLELE for white eyes exhibit
  white eyes!

17
IN CLASS EXERCISE

• Apply techniques learned in class (i.e. Punnet
  Square) to predict F1 genotype and phenotype of
  the following cross
• Red-eyed Female x White-eyed Male
• (homozygous)

SYMBOLS Red eye w Male XY White eye
w Female XX
18
IN CLASS EXERCISE

• Now, Perform Reciprocal Cross
• White-eyed Female x Red-eyed Male

X
19
MORGAN Drosophila
First half of reciprocal cross
Second half of reciprocal cross
Father
Mother
Mother
Father
Parental generation
Parental generation
XwXw
XwY
XwXw
XwY
Male gametes
Male gametes
Y
Xw
Y
Xw
Xw
Xw
F1 generation
Female gametes
Female gametes
F1 generation
XwXw
XwY
XwXw
XwY
Females
Males
Males
Females
Resulting phenotypes F1 females are red-eyed
F1 males are white-eyed
Resulting phenotypes All offspring are red-eyed
Red eye allele w White eye allele w
Female XX Male XY
20
IN CLASS EXERCISE

• Finally, cross F1 progeny from original cross
• Red-eyed Female x Red-eyed Male

X
21
MORGAN Drosophila
Crossing the F1 offspring
Mother
Father
F1 generation
XwXw
XwY
Male gametes
Y
Xw
Xw
XwXw
XwY
F2 generation
Female gametes
Xw
XwY
XwXw
Females
Males
Resulting phenotypes All F2 females are
red-eyed 1/2 of F2 males are red-eyed
22

MORGAN Drosophila

• Morgans work with Drosophila provided evidence
  that
• The X chromosome contains genes the Y doesnt
• Inheritance patterns of sex-linked genes vary
  between sexes
• Recessive traits more prevalent in males
• Genes are located on chromosomes
• Later supported by other scientists

23
LINKAGE

• Linkage
• Physical association of genes found on the SAME
  chromosome that influence different traits

24
LINKED GENES

• Linked genes are those that reside on the same
  chromosome and tend to be inherited together
• Autosomal Genes
• Reside on the autosomal chromosomes
• In humans genes are located on chromosome 1-22
• Sex-Linked Genes
• Found on sex chromosomes
• In humans genes found on pair 23 (usually on
  the X)

25
MORGAN LINKED GENES

• First examples of linked genes were found on X
  chromosome of Drosophila
• Morgan established that eye color body color
  are linked traits
• Both found on X chromosome of fruit fly

26
MORGAN LINKED GENES

• Morgan re-evaluated Mendels Principle of
  Independent Assortment
• Morgan predicted
• Linked genes should be transmitted together
  during gamete formation
• Genes on the same chromosome should NOT undergo
  independent assortment

27
LINKAGE HYPOTHESIS

• Hypothesis (Morgan)
• When two genes occur on one
• chromosome (linked), INDEPENDENT
• ASSORTMENT DOES NOT OCCUR

White eyes
A Female (2X chromo)
w w
Red eyes
Body Color Gray body wild type (y) Yellow
body mutant (y)
w w
Gray body
y y
y y
Yellow body
Eye Color Red wild type (w) White
mutant (w)
Meiosis I
w w
w w
y y
y y
Meiosis II
w
w
w
w
Gametes
y
y
y
y
wy
wy
ONLY 2 gamete types
28
Results of cross are notAs Morgan predicted!!
MORGANS TEST OF THE LINKAGE HYPOTHESIS
Linkage hypothesis
Result of Cross NOT As Morgan Predicted!
Female
Male
X
Parental generation
Red eyes
White eyes
w
w
w
w
Xwy / Y
Xwy/ Xwy
Yellow body
Gray body
y
y
y
y
Female
Male
F1 generation
X
Meiosis I
w
w
w
w
Xwy/ Y
Xwy/ Xwy
y
y
y
y
F2 generation MALES ?
Eye Color Red wild type (w) White
mutant (w)
Phenotype
Genotype
Number
Meiosis II
Xwy /Y
4292
Xwy /Y
w
w
w
w
4605
Gametes
y
y
y
y
Xwy /Y
Novel genotypes
86
86
Xwy/Y
44
wy
wy
Hypothesis When two loci occur on one
chromosome, meiosis results in two, rather than
four, types of gametes because independent
assortment does not occur.
Results There are four kinds of male offspring
rather than two!!
Body Color Gray body wild type (y) Yellow
body mutant (y)
29
LINKAGE HYPOTHESIS

• Results of test could NOT be explained by the
  linkage hypothesis alone.
• Two of four (male) phenotypes NOT predicted
• Crossovers during Meiosis I may be the answer

30
RECOMBINATION

• Genetic Recombination
• Production of offspring with a new combination of
  traits
• Linked genes become unlinked through
  recombination
• Ex Crossover (during meiosis)

31
Morgans Assumption w linked to y w linked to y
There are four kinds of gametes (eggs) rather
than two due to crossing over in small of F1
females (during Meiosis I)
Female Cell ? 2 X Chromosomes
w
w
y
Y
Y
y
Crossing over during meiosis I
w
w
w
w
Y
y
y
Y
Meiosis II
w
w
w
w
Gametes
Y
y
Y
y
wy
w y
wy
wy
Recombinant chromosomes
Recombination provides explanation for
unexpected phenotypes in F2 males
32
RECOMBINATION

• In absence of crossing over, there are 2 types of
  gametes (as predicted by Morgan)

w
w
w
Meiosis I II
w

y
y
y
y
Gamete 1
Gamete 2
Parent Cell
33
RECOMBINATION

• A cross over event results in 2 new combinations
  

w
w
Meiosis I II
w
w

y
y
y
y
crossover
Recombinant Gametes
Parent Cell
34
RECOMBINATION PROBABILITY

• The farther apart two genes, the higher the
  probability they will be separated during
  crossover
• Genes far apart on chromosome are more likely to
  be separated
• Genes close together are less likely to be
  separated

35
RECOMBINATION PROBABILITY

• A D are more likely than B C to become
  separated (unlinked)
• B C more likely to be inherited together (stay
  linked)

B
C
A
D
36
GENE MAPPING

• Maps of genes can be constructed from
  recombination data
• Recombination data reflects distance between
  2 loci

Linkage map genetic map based on recombination
frequencies
Crossing Over
37
GENE MAPPING
recombinant gametes reflects distance between 2
loci
Gene 1
Crossing over rarely occurs between adjacent
loci, recombinations are rare.
0 Yellow body
0 Yellow body
0 Yellow body
Gene 2
1.4 White eyes
1.4 White eyes
Gene 3
Gene 4
Map units
Gene 5
Gene 6
Gene 7
20 Cut wings
Crossing over almost always occurs
between distant loci, recombinations are
frequent.
Gene 8
Gene 9
Gene 10
Gene 11
Gene 12
Linkage map
Chromosomes are composed of genes
The physical distance between loci determines the
frequency of crossing over.
Frequency of crossing can be used to map physical
between loci.
38
GENE MAPPING

• If of recombinant gametes is high, 2 genes are
  assumed to be far apart on a chromosome
• Map Unit refers to distance between 2 loci
• Function of recombinants