Biology Reference
In-Depth Information
(A)
Fitness: wild-type = 1; single mutant
a
= 0.8
1.0
Positive
genetic
interactions
Non-essential
protein complex
0.9
A
Symmetric:
a
b
Suppression:
a
b
>
min(
a
,
b
)
=
a =
b
a
b
>
a
×
b
Linear
pathway
B
C
0.8
A
Masking
(epistasis):
a
×
b
<
ab
≤
min(
a
,
b
)
0.7
B
Activation/
repression
0.6
function
B
A
0.5
C
Negative
genetic
interactions
Parallel
pathways
function
0.4
A
B
a
b
<
a
×
b
Synthetic sick:
0
<
a
b
<
a
×
b
0.3
C
D
0.2
function
0.1
Synthetic lethal:
a
b =
0
0.0
0.0
0.1
0.2
0.3
0.5
0.6
0.7
0.8
1.0
0.4
Single mutant fitness
b
0.9
(B)
A
B
C
D
E
F
G
HI JKLMNO
A
High
correlation
Protein
complex
B
C
Low
correlation
X
D
Protein
complex
E
High
correlation
F
G
C
Force-directed
network layo
ut
D
A
E
B
X
D
F
B
E
C
F
G
G
X
A
FIGURE 6.1
(A) A graphical representation of quantitative genetic interactions. In the illustrated scenario, the fitness of the wild-type and one of the
single mutants (a) is assumed to be 1.0 and 0.8, respectively. The fitness of mutant b can vary between 0.0 and 1.0 and is plotted on the x-axis. The expected
fitness of the resultant ab double mutant based on a multiplicative model (a
b) is 0.8
b and is plotted as a solid black line. The observed double mutant
fitness (ab) is plotted on the y-axis. Negative genetic interactions. Negative deviations from the expected fitness are scored as either synthetic sick or
synthetic lethal interactions (pink area). Negative genetic interactions commonly occur between genes that function in parallel pathways to regulate the same
essential function. Symmetric positive interactions. Themeasured fitness of the ab doublemutant (0.8) is greater than themultiplicative expectation (0.64),
indicating a positive genetic interaction. The interaction is classified as symmetric because the two single mutants (a and b) and the resultant double mutant
(ab) exhibit the same fitness (ab
¼
a
¼
b
¼
0.8). Symmetric positive interactions are frequently observed between genes encodingmembers of the same non-
essential protein complex. Asymmetric positive interactions. In this scenario, single mutants and double mutants differ in fitness. Positive deviations from
expectation (green area) along with single mutant fitness comparisons allow the classification of asymmetric positive interactions into different subcate-
gories, including masking interactions (light green area) and suppression (darker green area). Masking describes positive interactions where the double
