Q1 - C. elegans Apoptosis Gene Network
The effect of knocking out specific genes in worms on apoptosis (programmed cell death) was studied.
| GENE | MANIPULATION | CELL DEATH |
|---|---|---|
| ced9 | knock-out | increased |
| ced4 | knock-out | reduced |
| ced3 | knock-out | reduced |
| egl1 | knock-out | reduced |
| ced4 & ced9 | knock-out | reduced |
| ced9 & ced3 | knock-out | reduced |
| ced9 & egl1 | knock-out | increased |
This question originally asked you to fill in a four-box pathway diagram on a separate physical answer sheet (not part of this PDF) - reproduced here as two free-response questions instead, working from the same epistasis data.
Q1.1. The effect of knocking out ced9, ced4, ced3 and egl1 (singly and in the pairwise combinations ced4&ced9, ced9&ced3, ced9&egl1) on apoptosis was studied (see the table on the question page). Using this epistasis data, write the letters A (Ced3), B (Ced4), C (Ced9) and D (Egl1) into the correct position of a four-step linear pathway model of the control of cell death (CD).
Pathway order: Egl1 (D) ⊣ Ced9 (C) ⊣ Ced4 (B) → Ced3 (A) → cell death (CD).: Epistasis logic: ced9 knock-out alone INCREASES death, so Ced9 normally suppresses death. ced4, ced3 and egl1 knock-outs alone all REDUCE death, so each normally promotes death. In the double knockouts, ced4&ced9 and ced9&ced3 both give the REDUCED phenotype (i.e. ced4/ced3 are epistatic to ced9, they act downstream of it), while ced9&egl1 gives the INCREASED phenotype (ced9 is epistatic to egl1, ced9 acts downstream of egl1). That ordering, egl1 upstream of ced9, ced9 upstream of ced4/ced3, matches the real, well-characterised C. elegans apoptosis pathway: EGL-1 inhibits CED-9; CED-9 inhibits CED-4; CED-4 activates the executioner caspase CED-3. The official key credits either order for the Ced3/Ced4 pair at the two downstream positions.
Q1.2. Indicate whether each of the three interactions in the pathway above (D⊣C, C⊣B, B→A) is activating (+) or repressing (-).
Egl1 ⊣ Ced9: repressing (-). Ced9 ⊣ Ced4: repressing (-). Ced4 → Ced3: activating (+).: Directly follows from the epistasis reasoning above: Egl-1 represses Ced-9, Ced-9 represses Ced-4, and Ced-4 activates Ced-3 (which then executes cell death).
Question reproduced from IBO 2019, Theoretical Exam A, licensed under CC BY-NC-SA 4.0 - attributed to the International Biology Olympiad. Open the full exam PDF · Official answer key