Gene Interaction-PART 2

Todays lecture (0122)

Mendels Dihybrid Cross - the 9:3:3:1 ratio
Revisited
Concept of genetic interaction between alleles at
two different loci.
The 9:3:3:1 ratio no gene interaction
Epistasis
The 9:7 ratio genes in the same pathway
Suppressors, mofidiers and Synthetic lethals.
Penetrance and expressivity

Mendels dihybrid cross

Mendels dihybrid cross:
- two different genes (R, r or Y, y)
- each gene had an independent phenotypic
effect:
seed shape (round or wrinkled)
and seed color (yellow
or green)
- i.e. 2 genes, 2 phenotypes and genes do not
interact
(Y or y affect only seed color and do not
affect seed
shape and vice versa for the R and r
alleles for seed
shape)

Dihybrid Cross

Dihybrid Cross
All of the 16 genotypes of the F2 fall
in these 4 genotype categories:

R/- ; Y/- : round, yellow 9

R/- ; y/y : round, green 3
r/r ; Y/- : wrinkled, yellow 3
r/r ; y/y : wrinkled, green 1

Dihybrid Cross
In general, for a dihybrid cross between two double
heterozygotes (heterozygous at two genetic loci):
A/a ; B/b X

A/a ; B/b

A/- ; B/- : 9
Genotype Categories:
A/- ; b/b : 3
a/a ; B/- : 3
a/a ; b/b : 1

Interactions between alleles of two

different genes

Genes may not always act independently in their

phenotypic expression

Genes at one locus can affect genes at another locus

and products of genes at different loci combine to
produce a new phenotype = Gene interaction
Gene interactions change Mendelian phenotypic
ratios (do not get 9:3:3:1 ratio)

Interactions between alleles of two

different genes

The 9:3:3:1 ratio: no gene interaction

Eg: skin coloration in Corn snakes:

Natural coloration: Black and orange camouflage pattern determined

by two separate genes each producing a separate pigment:
Alleles at orange pigment locus : o+ (orange pigment) , o (no orange
pigment)
Alleles at black pigment locus: b+ (black pigment), b (no black
pigment)

Orange-Black
orange)

Black (no

Orange (no
black)

Albino (no
orange, no

Interactions between alleles of two

different genes
Orange-black (camouflage) : o+/-; b+/ Black (lacks orange)

: o /o; b+/-

Orange (lacks black)

: o+/-; b /b
Albino (no black, no orange): o /o ; b /b
o+/o+; b/b (orange) x o/o ; b+/b (black)

F1:
Self F1

o+/o ; b+/b (camouflaged)

o+/o ; b+/b x o+/o ; b+/b

F2: 9 o+/-; b+/- (camouflaged)

3 o+/-; b/b (orange)
3 o/o; b+/- (black)

Interactions between alleles of two

different genes

The 9:7 ratio, genes in same pathway:

Eg: Blue-white flower color in harebell plants:

- Wild-type flower color is blue and mutant flower color is white

- Blue color is due to pigment called anthocyanin.
- Anthocyanin absorbs light of all wavelengths except blue and
reflects
blue which is the color of flower seen.
- Anthocyanin made from precursors by
enzymes
-

If enzyme for anthocyanin is defective:

o anthocyanin not functional,
o precursors do not absorb light but reflect it
back
o flower appears white

Interactions between alleles of two

different genes

The 9:7 ratio, genes in same pathway:

- Biochemical pathway for synthesizing anthocyanin:

gene w1+

gene w2+

precursor 1 enzyme 1 precursor 2 enzyme 2 anthocyanin

(blue)
-

Mutation in either w1+ or w2+ = NO ANTHOCYANIN, FLOWER

WHITE
Genotypes:

w1+/w1+ ; w2+/w2+ = blue

w1/w1 ; w2+/w2+ = white
w1+/w1+ ; w2/w2 = white

Interactions between alleles of two

different
genes

The 9:7 ratio, genes in same pathway:

P

w1/w1 ; w2+/w2+ (white) X w1+/w1+ ; w2/w2 (white)

Gametes

w1; w2+

w1+; w2

w1+/w1 ; w2+/w2 (blue)

F1

w1+/w1 ; w2+/w2 (blue) X

Self F1
Gametes
F2

w1+;w2+ w1+;w2 w1;w2+ w1;w2

w1+/w1 ; w2+/w2 (blue)

w1+;w2+ w1+;w2 w1;w2+ w1;w2

9/16 w1+/- ; w2+/ - (blue)

3/16 w1+/- ; w2/w2 (white)
3/16 w1/w1 ; w2+/- (white)
1/16 w1/w1 ; w2/w2 (white)

9 Wild-type
Single mutant
7 Single mutant
Double

Interactions between alleles of two

different genes

The 9:3:4 ratio: Recessive Epistasis

-

Labrador dogs can be black, brown or yellow.

Interactions between alleles of two

different genes

The 9:3:4 ratio: Recessive Epistasis

- Coat color determined by interaction between 2 gene loci.

- Gene locus 1: type of dark skin pigment:
allele B: black pigment, dominant
allele b: brown pigment, recessive
-

Gene locus 2: deposition of the pigment in the shaft of the hair:

allele E: deposition of pigment (black or brown),

dominant
allele e: prevents deposition of pigment (yellow),
recessive
-

Genotype ee at the second locus masks expression of the black

and brown alleles at the first locus. (i.e. -/-, e/e = yellow)

Epistasis is an effect of gene interaction such that one gene

masks (hides) the effect of another gene at a different locus.

Interactions between alleles of two

different genes

The 9:3:4 ratio: Recessive Epistasis (coat color of Labrador dogs)

Cross a black labrador homozygous for the dominant alleles at both
gene loci with a yellow labrador homozygous for the recessive
alleles at both gene loci
P
B/B; E/E (Black) x b/b; e/e (Yellow)
Gametes

B;E

F1
Self F1

b;e
B/b; E/e (Black)

B/b;E/e (Black) x B/b;E/e (Black)

F2

9/16 B/-;E/- (Black)

3/16 b/b;E/- (Brown)

9
3

3/16 B/-;e/e (yellow)

1/16 b/b;e/e (yellow)
Phenotypic ratio =

4 (-/-;e/e)

Black: Brown: Yellow= 9:3:4

READ ABOUT PETAL PIGMENT SYNTHESIS IN BLUE-EYED

Interactions between alleles of two

different genes

The 9:3:4 ratio: Recessive Epistasis

- Genotype ee at the second locus masks expression of the black

and brown alleles at the first locus.
-

Epistasis is an effect of gene interaction such that one gene

masks (hides) the effect of another gene at a different locus.

Gene that does the masking = epistatic gene (pigment

deposition)

Gene whose effect is masked = hypostatic gene (coat color

pigment)

Recessive epistasis: Recessive allele at second locus (no pigment

deposition) overrides pigment color phenotype determined by
first locus.

Interactions between alleles of two

different genes

The 12:3:1 ratio: Dominant Epistasis:

Eg: Petal coloration in Foxgloves

Interactions between alleles of two

different genes

The 12:3:1 ratio: Dominant Epistasis:

Eg: Petal coloration in Foxgloves

- Petal coloration determined by interaction between 2 gene loci.

- Gene locus 1: intensity of red pigment in petal:
allele d: light red color, recessive (seen
naturally)
allele D: dark red color, dominant (mutant)
- Gene locus 2: distribution of pigment in petals (light or dark red):
allele w: pigment synthesized throughout petal,
recessive
allele W: white

petal with red throat spots,

dominant
-

Genotype W/- at the second locus masks distribution of the red

pigment throughout petal.(i.e. -/-; W/- = white petals with spots)

Interactions between alleles of two

different genes

The 12:3:1 ratio: Dominant Epistasis (Petal coloration in

Foxgloves)
Cross
flowers that have white petals and red throat spots,
homozygous for the dominant alleles at both gene loci with a flower
with light red petals, homozygous for the recessive alleles at both
gene loci
P
D/D; W/W (White with spots) x d/d; w/w (Light Red)
Gametes

D;W

F1

d;w
D/d;W/w (White with spots)

D/d;W/w (White with spots) x D/d;W/w (White with spots)

F2
(-/-;W/W)

Phenotypic ratio =
12:3:1

9/16 D/-;W/- (White with spots) 12

3/16 d/d;W/- (White with spots)
3/16 D/-;w/w (Dark red)

1/16 d/d;w/w (Light red)

White with spots: Dark red: Light red=

Interactions between alleles of two

different genes

Suppressors
- A mutant allele of one gene that reverses the effect of a
mutation at another gene, resulting in wild-type
phenotype
-

Suppressor gene and target gene must interact at functional

level in wild-type state

Eg: Drosophila eye color

Gene locus 1: Eye color:
allele pd: purple color, recessive (mutant)
allele pd+: red color, dominant (wild-type)
Gene locus 2: Suppressor (no independent phenotype):
allele su: suppresses pd, recessive
allele su+: No suppression of pd, dominant

Interactions between alleles of two

different genes

Suppressors: (Drosophila eye color)

Cross a homozygous purple-eyed fly with a homozygous red-eyed
fly carrying the suppressor
pd/pd; su+/su+ (Purple) x pd+/pd+; su/su (Red)

P
Gametes
F1

pd; su+

pd+; su

pd+/pd; su+/su (Red)

pd+/pd; su+/su (Red) x pd+/pd; su+/su (Red)

F2

9/16 pd+/-; su+/- (Red)

3/16 pd+/-; su/su (Red)

13

1/16 pd/pd; su/su (Red)

double

mutant
3/16 pd/pd; su+/- (purple)

Interactions between alleles of two

different genes

Suppressors: Molecular Mechanism

1. If mutation blocks a metabolic pathway, suppressor bypasses
the block
(eg: by rerouting into intermediates similar to those in the
pathway
beyond the block)
No suppressor:
A
B
product
With suppressor:
Block
A
B
product
B
2. If two proteins need to interact to provide a phenotype. If
mutation in one changes its shape such that it cannot interact with
second protein = no function. But, if suppressor mutation in the
second protein causes a change its shape so that it can interact
with the mutated version of first protein, then function restored
(see next slide)

Interactions between alleles of two

different genes

Suppressors: Molecular mechanism

F2:
m+/m.

s+/s x m+/m.

s+/s
m+/- . s+/-: active 9
m/m . s+/s: active
2 14
m+/m . s/s: active
2
m/m . s/s: active

Interactions between alleles of two

different genes

Modifiers:
- Instead of one gene masking the phenotypic effect of another
gene, it may modify the expression of the second gene.

Eg: Coat color in mice:

Gene Locus 1: Gene for Coat color:
Allele B = black coat
Allele b = brown coat
Gene Locus 2: Intensity of coat color:
Allele D = full color (black or brown)
Allele d = diluted expression of B or b alleles

Interactions between alleles of two

different genes

Modifiers:
F1
Self F1

B/b; D/d (Black)

B/b;D/d (Black) x B/b;D/d(Black)

F2

9/16 B/-; D/- (Black)

3/16 b/b; D/- (Brown)
3/16 B/-; d/d (dilute black)
1/16 b/b; d/d (dilute brown)

Phenotypic ratio =
brown= 9:3:3:1

Black: Brown: dilute black: dilute

Allele at locus for intensity of coat color doesnt mask, but

modifies, the effect on coat color

Interactions between alleles of two

different genes

Synthetic Lethals:
1. Crossing two single mutants results in double mutants (eg: a
and b are
mutant alleles at 2 different gene loci) that are lethal:
self the F1 :

F2:

a+/a ; b+/b X

a+/a ; b+/b

a+/- ; b+/- : 9
a+/- ; b/b : 3
a/a ; b+/- : 3
a/a ; b/b : 1
Ratio = 9:3:3

Lethal

Interactions between alleles of two

different genes
Synthetic Lethals: Molecular Mechanism
1. Duplicate systems in cells as a backup. If null mutations in
both
systems -> No backup ->cell death
2. Two interacting proteins perform
essential function on a substrate
such as DNA but must first bind to
it.
Reduced binding of either protein
causes some functions to remain
but
reduced binding of both is lethal.

Interactions between alleles of two

different genes

Penetrance and Expressivity

Penetrance = % of individuals with a given allele that express
the phenotype associated with that allele
If 100 individuals have an allele for blue eye color and all have
blue eyes, the allele is 100% penetrant into the phenotype
If not, the allele is incompletely penetrant
Reasons:
- Environment
- Influence of other interacting genes
- If it is a mutant allele, the effects on
phenotype may be subtle

A dominant allele is not

fully penetrant

Penetrance and Expressivity

Expressivity: Measures the degree/extent of phenotypic
expression of a given allele (i.e. intensity of phenotype)
Eg: piebald spotting in beagles. Each has allele for piebald
spotting but there is variation in extent of spotting.

Penetrance and Expressivity

Penetrance vs. expressivity

Learning Outcomes
You should be able to:
Explain the concept of gene interaction with respect to
interactions between alleles at two different gene loci.
Solve genetic problems based on genetic interaction
between two genetic loci.
Explain the difference between Recessive and
Dominant epistasis.
Describe the molecular mechanisms underlying the
effects of modifier and suppressor alleles.
Explain the difference between penetrance and
expressivity.

Learning Outcomes
You should be able to:
Describe the molecular mechanisms underlying the
effects of modifier and suppressor alleles.
Explain the difference between penetrance and
expressivity.