Lecture 10

More variations on Mendelian Inheritance

4. Three or more alleles of a single gene

5. Multiple genes that affect the same trait/Duplicate genes

6. Epistasis


Complementation testing - are two mutations in
the same gene or in different genes?
1

We discussed :

1. Incomplete dominance

2. Co-dominance

3. Recessive lethal alleles
2
4. Multiple alleles one gene can have more than two alleles.

Example: For the ABO blood types the third allele i is a recessive allele that gives the O blood
type. It is fully recessive to I
A
and I
B


ii I
A
i I
A
I
B
I
B
i
Type O Type A Type AB Type B
A
A
A
A
B
B
B
B
A
A
A
A
B
B
B
B
3
Offspring from a mating between i I
A
and i I
B

parents can produce four phenotypes
i I
A
i
I
B
i i i I
A
i I
B
I
B
I
A
i i - type O
i I
A
type A
i I
B
- type B
I
B
I
A
- type AB
4
The compatibility of blood donors and blood recipients is
determined by their blood types.
This summarizes the ABO compatibilities.
Blood type Antigen Antibody Can Can receive
donate to from

type O none anti A and B all O only
type A A anti B A and AB O and A
type B B anti A B and AB O and B
type AB A + B none AB all
Rh positive and negative blood types are determined
by another gene, which has two alleles
5
Beetles of a certain species may have green, blue or turquoise
wing covers. From the results of crosses listed below deduce the
basis of inheritance of wing cover color and write the genotypes
of the parents and progeny.

Cross Parents Progeny
-------------------------------------------------------------------------------
1. blue x green all blue
2. blue x blue 3/4 blue : 1/4 turquoise
3. green x green 3/4 green : 1/4 turquoise
4. blue x turquoise 1/2 blue : 1/2 turquoise
5. blue x blue 3/4 blue 1/4 green
6. blue x green 1/2 blue : 1/2 green
7. blue x green 1/2 blue : 1/4 green : 1/4 turquoise
8. turquoise x turquoise all turquoise
6
Cross Parents Progeny
-------------------------------------------------------------------------------
1. blue x green all blue
2. blue x blue 3/4 blue : 1/4 turquoise
3. green x green 3/4 green : 1/4 turquoise
4. blue x turquoise 1/2 blue : 1/2 turquoise
5. blue x blue 3/4 blue 1/4 green
6. blue x green 1/2 blue : 1/2 green
7. blue x green 1/2 blue : 1/4 green : 1/4 turquoise
8. turquoise x turquoise all turquoise
A. Note ratios are 3:1 , 1:1 or 1:2:1
Therefore the trait is likely controlled by one gene.
B. 3:1 ratios suggests there is Complete Dominance.
There are three alleles.
blue is dominant to turquoise (Cross 2)
blue is dominant to green (Cross 1, 5)
green is dominant to turquoise (Cross 3)
7
B
B
> B
g
> B
t
Blue is dominant to green,
green dominant to turquoise

Cross Parents Progeny
-------------------------------------------------------------------------------
1. blue x green all blue
2. blue x blue 3/4 blue : 1/4 turquoise
3. green x green 3/4 green : 1/4 turquoise
4. blue x turquoise 1/2 blue : 1/2 turquoise
5. blue x blue 3/4 blue 1/4 green
6. blue x green 1/2 blue : 1/2 green
7. blue x green 1/2 blue : 1/4 green : 1/4 turquoise
8. turquoise x turquoise all turquoise
8
B
B
> B
g
> B
t
Cross Parents Progeny
-------------------------------------------------------------------------------
1. blue x green all blue
B
B
B
B X
B
g
B
g
B
B
B
g
2 blue x blue 3/4 blue : 1/4 turquoise
B
B
B
t
x B
B
B
t
1/4 B
B
B
B
1/2

B
B
B
t
1/4 B
t
B
t

green x green 3/4 green : 1/4 turquoise
blue x turquoise 1/2 blue : 1/2 turquoise
blue x blue 3/4 blue 1/4 green
blue x green 1/2 blue : 1/2 green
blue x green 1/2 blue : 1/4 green : 1/4 turquoise
turquoise x turquoise all turquoise
9
B
B
> B
g
> B
t
Parents Progeny
1. blue x green all blue
B
B
B
B X
B
g
B
g
B
B
B
g
2. blue x blue 3/4 blue : 1/4 turquoise
B
B
B
t
x B
B
B
t
1/4 B
B
B
B
1/2

B
B
B
t
1/4 B
t
B
t

3. green x green 3/4 green : 1/4 turquoise
B
g
B
t
x B
g
B
t
1/4 B
g
B
g
1/2

B
g
B
t
1/4 B
t
B
t
4. blue x turquoise 1/2 blue : 1/2 turquoise
B
B
B
t
x B
t
B
t
1/2 B
B
B
t
1/2

B
t
B
t

5. blue x blue 3/4 blue 1/4 green
B
B
B
g
x B
B
B
g
1/4 B
B
B
B
1/2

B
B
B
g
1/4 B
g
B
g

6. blue x green 1/2 blue : 1/2 green
B
B
B
g
x B
g
B
g
1/2 B
B
B
g
1/2

B
g
B
g

7. blue x green 1/2 blue : 1/4 green : 1/4 turquoise
B
B
B
t
x B
g
B
t
1/4 B
B
B
g


1/4 B
B
B
t
1/4

B
g
B
t
1/4 B
t
B
t

8. turquoise x turquoise all turquoise
B
t
B
t
x B
t
B
t
B
t
B
t
10
5. Multiple genes affecting the same trait

Example: 2 hair color genes in mice.
BB and Bb - black
bb - brown
AA, Aa - agouti (yellow band near the tip of the hair)
aa - solid color.

AaBb x AaBb

9 A_B_ agouti - black with a yellow band
3 A_bb cinnamon brown with a yellow band
3 aaB_ black
1 aabb brown
11
Black
hair
Agouti
hair
12
AaBb x AaBb


9 A_B_ agouti
3 A_bb cinnamon
3 aaB_ black
1 aabb brown
9 : 3 : 3 : 1
13
Duplicate genes
Modern analysis of genomes of several organisms
has shown that gene duplication in the evolutionary
history of an organism is common.

If a duplicate gene is located on a different chromosome
than the original gene and the two copies maintain
their original function, they will generate an inheritance
pattern of 1:15 in a F2 population resulting from the cross
of the homozygous duplicate to a recessive strain
14
Duplicate genes
controlling fruit shape
in Shepard's Purse.

Two genes with two
alleles with dominance
and recessive relationships.

Only the individuals
homozygous recessive for
both genes have
narrow fruit 1 / 16.
15
A1a1 A2a2 X A1a1 A2a2
A1 A2 A1 a2 a1 A2 a1 a2

A1A2 A1A1 A1A1 A1a1 A1a1
A2A2 A2a2 A2A2 A2a2

A1a2 A1A1 A1A1 A1a1 a1A1
A2a2 a2a2 A2a2 a2a2

a1A2 A1a1 A1a1 a1a1 a1a1
A2A2 A2a2 A2a2 A2a2

a1a2 A1a1 A1a1 a1a1 a1a1
A2a2 a2a2 A2a2 a2a2
16
In recent years the degree of gene duplication in in
eukaryotic organisms has been a surprising discovery
of genetic research.

The gene duplication is obvious from DNA
sequence analysis, however the duplicates
are not 100% identical.

Whether duplicated genes have maintain their original
function or have evolved new functions is not obvious.
It is a subject of ongoing research.
17
The salivary amylase enzyme encoded by the AMY1 gene is
important for digestion of starch.

A comparison of AMY1 in high-starch eaters
Americans of European descent, Japanese,
Hadza from Tanzania, hunter-gatherers who
eat many roots and tubers
have 7 copies of AMY1

The Biaka of the Central African Republic and Mbuti from Congo,
both rainforest hunter-gatherers, and Tanzania's Datog and
Siberia's Yakut pastoralists, groups that eat little starch,
averaged 5 copies AMY1

Chimpanzees, eat little starch have only two copies of AMY1
Bonobos relatives of chimpanzees have an inactive mutated
version of AMY1.
Science 14 September, 2007 317: 1483
Photo: F. MARLOWE/FLORIDA STATE UNIVERSITY
18
6. Epistasis

Epitasis occurs when the alleles of one gene masks the effects of
alleles of another gene. This modifies an expected 9:3:3:1 ratio
Example: c is a recessive allele of the C gene responsible
for albinos.
It is epistatic to the B/b gene for black and brown hair, i.e.
individuals who are cc will be white no matter the allele
carried for the brown/black gene.

BBCC - are black
bbCC - are brown
BBcc - are albino
bbcc - are albino
19
BbCc x BbCc

B_C_ - black 9
bbC_ - brown 3
B_cc - albino 3
bbcc - albino 1
4
BBCC - are black
bbCC - are brown
BBcc - are albino
bbcc - are albino
Ratio 9 : 4 : 3
20
Complementation
21
The blue pigment in
lobleia is
Delphinidin-3-glucoside.
The precursor of this compound
is Leucodelphinidin, which is
colorless.
The enzyme for this
synthesis
is an Anthocyanin
3-glucotransferase.
22
The mutation for white color is recessive. With only
one active copy of the gene there is sufficient pigment
produced to have blue flowers.
23
Complementation test:

Do two mutants have mutations in the
same gene or in different genes?
24
Individual crosses can tell us that each white mutation is caused a recessive allele of a gene.

But we would not know if the two white mutations are in the same gene or not.
x x
x
x
P


F1



F2
w1
w2
P


F1



F2
25
Compound A
(white)
Compound B
(white)
Compound C
(blue)
Gene W1+ Gene W2+
Enzyme 1 Enzyme2
Gene W1+ Gene W2+
White 1 White 2
It is possible that there are two genes in pathway for the
Synthesis of blue pigment. A mutation in either gene could
give a white phenotype
26
Compound A
(white)
Compound B
(white)
Compound C
(blue)
Gene w1-- Gene W2+
Enzyme 1 Enzyme2
Gene w1-- Gene W2+
A mutation in W1 blocks the pathway
no blue pigment is produced.
the flower is white.
27
Compound A
(white)
Compound B
(white)
Compound C
(blue)
Gene W1+ Gene w2--
Enzyme W1+ Enzyme2
Gene W1+ Gene w2--
A mutation in W2 blocks the pathway.
No blue pigment is produced.
The flower is white.
28
Gene W1+ Gene w2

(W1+W1+, w2-- w2--)
Gene W1+ Gene w2--
Gene w1-- Gene W2+

(w1-- w1--, W2+ W2+)
Gene w1-- Gene W2+
X
Gene w1-- Gene W2+
Gene W1+ Gene w2--
To test whether two white mutants have mutation in the same
Gene or in different genes we can cross them. This is called a
complementation test.
x
What color would
you predict for
the offspring?
29
Gene W1+ Gene w2

(W1+W1+, w2-- w2--)
Gene W1+ Gene w2--
Gene w1-- Gene W2+

(w1-- w1--, W2+ W2+)
Gene w1-- Gene W2+
X
Gene w1-- Gene W2+
Gene W1+ Gene w2--
x
30
Compound A
(white)
Compound B
(white)
Compound C
(blue)
Enzyme 1 Enzyme2
Gene w1-- Gene W2+
Gene W1+ Gene w2--
The plant that is heterozygous for the
w1 and w2 mutation has a functional
copy of each gene, it produces both
critical enzymes. The blue pigment is produced.
31
Most mutations inactivate a gene or the protein encoded by
the gene.

Most mutations are recessive.

To determine if two mutants have mutations in
different genes we do a complementation test
- the two mutants are crossed.
(This test only works if the mutations are recessive)

If the F1 from the cross is wild type, it indicates the
2 mutations are in different genes
X
32
(W1+W1+, w2-w2-)
(w1-- w1--, W2+ W2+)
X
F1 w1-W1+ w2-W2+ X w1-W1+ w2-W2+
9. W1+__ W2+__

3. w1-w1- W2+__

3 W1+__ w2-

1 w1-w1- w2-w2-
9
7
These mutations
complement each
other; they are in
different genes.
33
1 2 3 4 5 6 7 8 9 10 11 12
1 w + + + w + + + + + + +
2 w + + + w + w + w + +
3 w w + + + + + + + +
4 w + + + + + + + +
5 w + + + + + + +
6 w + w + w + +
7 w + + + w w
8 w + w + +
9 w + + +
10 w + +
11 w w
12 w

12 mutants in Caenorhabditis elegans that wiggled ineffectually instead of
gliding were isolated. The mutants were intercrossed and the F1 checked for
wiggling.
(a) Why?
(b) Assign genotypes to all 12 mutants.
(c) Why did F1 from crosses 1 x 2 and 1x 5 have different phenotypes?
34
1 2 3 4 5 6 7 8 9 10 11 12
1 w + + + w + + + + + + +
2 w + + + w + w + w + +
3 w w + + + + + + + +
4 w + + + + + + + +
5 w + + + + + + +
6 w + w + w + +
7 w + + + w w
8 w + w + +
9 w + + +
10 w + +
11 w w
12 w

Problem 66. 12 mutants in Caenorhabditis elegans that wiggled ineffectually instead of gliding were
isolated. The mutants were intercrossed and the F1 checked for wiggling.
(a) Why? These are complementation tests, they will show which mutations
are in the same gene.
(b) Assign genotypes to all 12 mutants.
(c) Why did F1 from crosses 1 x 2 and 1x 5 have different phenotypes?
35
1 2 3 4 5 6 7 8 9 10 11 12
1 w + + + w + + + + + + +
2 w + + + w + w + w + +
3 w w + + + + + + + +
4 w + + + + + + + +
5 w + + + + + + +
6 w + w + w + +
7 w + + + w w
8 w + w + +
9 w + + +
10 w + +
11 w w
12 w

Problem 66. 12 mutants in Caenorhabditis elegans that wiggled ineffectually instead of gliding were
isolated. The mutants were intercrossed and the F1 checked for wiggling.
(a) Why? These are complementation tests, they will show which mutations
are in the same gene.
(b) Assign genotypes to all 12 mutants.
(c) Why did F1 from crosses 1 x 2 and 1x 5 have different phenotypes?
w1
w2
w3
w3
w1
w2
w7
w2
w9
w2
w7
w7

36