Lecture 5: Genetic interactions and epistasis
A. Epistasis in a biochemical pathway
B. Epistasis in a regulatory pathway
C. Additive interactions
D. Synergistic interactions
E. Suppressions
Read 3.14 (p60-61); 7.23 (p232-234)
8.32 (p290-291); 8.5 (259-260)
1
What is epistasis?
A gene interaction in which the effects of an allele at one
gene hide the effects of alleles at another gene
2
Codominant blood group alleles
Fig. 3.4b 3
Molecular explanation for recessive epistasis in
human blood groups
• Two parents who
are apparently
type O have
offspring that is
type A or B on
rare occasions.
• Bombay
phenotype –
mutant recessive
allele at second
gene (hh) masks
phenotype of ABO
alleles
Fig. 3.14b 4
epistasis analyses (genetic interactions among different mutations)
A. Flavonoid biosynthetic pathway in maize
C2 CHI
CHALCONE FLAVANONE
F3H
A1 A2 BZ1 GLUCOSIDE
BZ2
FLAVAN-3,4-DIOL
DIHYDROFLAVONOL bronze
ANTHOCYANINS
Mt1, Mt2
Peonidin-3-(p-coumaroyl)-
rutinoside-5-gluciside
red5
2
WT: Red
Mutations in c2, a1, a2: Colorless
Mutations in bz1, bz2: bronze
Double mutants
C2/a1: colourless-but uninformative
bz1/a1: colorless-a1 comes before bz1
bz2/a1: colorless-a1 comes before bz2
For biosynthetic pathways, the phenotype of the earlier gene
in the pathway shows in the double mutant.
ie. the earlier-step mutant is epistatic to the late-step mutant
Determine relationship between a1 and c2 by feeding experiment:
add flavanone (naringenin): c2+naringenin = red
a1+naringenin = colorless
6
Fig. 7.23 Biochemical Pathways
Fig. 7.20
7 4
B. Regulatory pathways
Signal A B C D gene expression
Positive action-stimulate next step.
Null mutation makes insensitive to signal
Negative action-represses next step.
Null mutation makes the gene turned on at all time (constitutively)
b-: gene expression never turned on
even in the presence of the signal
d-: gene expression constitutively on
even in the absence of signal
b-d- = d- : constitutively on
For regulatory pathways, the phenotype of the later-acting genes
shows in the double mutant.
ie. the later-acting mutant is epistatic to the earlier-acting mutant
8 5
wt wt ctr1 ein2
ethylene air air ethylene
etr1
ctr ein2 :?
triple
Ethylene CTR1 (Kinase) EIN2
response
For regulatory pathways, the phenotype of the later-acting genes
shows in the double mutant.
ie. the later-acting mutant is epistatic to the earlier-acting mutant
9
C. Additive pathways
Double mutants of dissimilar phenotypes produce a combination
of both phenotypes
Indicate that the two mutations are in genes acting in
separate pathways
ap2-2 (flower abnormal) X gl (no trichome)
ap2-2 gl double mutant
abnormal flower and no trichome
10
ap2-2
gl1
11
D. Synergistic interactions (enhancement)
Two genes may act at the same step of a pathway
Or in parallel or (redundant) pathways
12
Cal-1
ap1-1
ap1-1 cal-1
ap1-1 cal-1
13
ap1-1 10
E . Suppression
Intrgenic suppressors
Extragenic suppressors
Allele-specific suppression
Suppressors are defined classically as mutations that
correct the phenotypic defects of another mutation
without restoring its wild-type sequence. Suppressors
may be intragenic (affecting the same gene) or they may
be extragenic (affecting a different gene).
14
Intragenic suppressor
Frameshift mutation caused by a single base insertion can
be suppressed by a second mutation that cause a single
base deletion downstream from the first mutation.
See Fig. 8.5 and p259-260.
15
Studies of frameshift mutations in bacteriophage
T4 rIIB gene
16
Fig. 8.5
Intragenic suppressors
WT
E. coli
tryptophan
synthase
Tyr
Gly
mut1 mut1 mut2
Tyr
Cys
Glu Glu
17
Extragenic suppressors
Mutation in one gene could correct the effect of a mutation in
another gene
Nonsense (information) suppressor
Mutations in genes whose protein products interact
18
• Nonsense
suppression
– (a) Nonsense
mutation that
causes
incomplete
nonfunctional
polypeptide
– (b) Nonsense-
suppressing
mutation causes
addition of amino
acid at stop
codon allowing
production of full
length
polypeptide.
Fig. 8.32 19
Extragenic suppressors
Particularly useful during genetic analyses, because they often
identify additional components of a biological system or process.
20
