Q2 - CLK Mutation and Circadian PER Oscillations

Theoretical A Real exam question - full text reproduced under IBO's CC BY-NC-SA 4.0 license

Hall, Rosbash and Young were awarded the 2017 Nobel Prize for their discoveries of the molecular mechanisms that control circadian rhythms. ‘Period’ (PER) is a gene of the Drosophila that undergoes strict circadian oscillations. Mutations to PER alter or abolish the periodicity and phase of these rhythms. Another gene regulating the circadian rhythm is ‘clock’ (CLK). Drosophila with a certain mutation in the CLK gene sometimes have disrupted circadian rhythms as shown in Table 1.

Condition	Genotype	Period of activity (h)	% arrhythmic
12 hr light : 12 hr dark	CLK +/+	24.3	0
12 hr light : 12 hr dark	CLK +/-	24.3	36
12 hr light : 12 hr dark	CLK -/-	24.2	86
Constant darkness	CLK +/+	24.3	1
Constant darkness	CLK +/-	24.8	47
Constant darkness	CLK -/-	ARR (arrhythmic)	100

Table 1.

Cloning revealed that these identified CLK mutant flies have a premature stop codon that truncates the protein, making it non-functional. To determine the in vivo regulatory pattern of the PER gene, they generated transgenic Drosophila strains carrying a luciferase cDNA fused to the promoter region of the PER gene. Then they assayed the activity of luciferase (quantified in counts/s) in Drosophila of the various CLK genotypes. Results are shown in Figure 1. Note that the luciferase activity is proportional to the expression of the examined gene.

Luciferase (PER-promoter) activity over five days for CLK+/+, CLK+/- and CLK-/- flies, alternating 12h light/12h dark. CLK+/+ shows the tallest, most sharply cycling peaks; CLK+/- cycles at the same times but with lower amplitude; CLK-/- is essentially flat throughout. Fig.1. Axis 1 = Time (hours), white bars represent a 12 hour period of light, dark bars represent a 12 hour period of darkness. Axis 2 = Counts per Second.

Indicate with an X if each of the following statements are true (T) or false (F).

Q2.1. Behavioural effects of CLK mutation are largely due to a defect in the degradation of circadian rhythm proteins, including PER.

Q2.2. The main effects of CLK mutation are fully penetrant at the molecular level.

Q2.3. The main effects of CLK mutation are fully penetrant at the behavioural level.

Q2.4. PER promoter activity cycled with a reduced frequency in CLK +/- flies compared to CLK +/+ flies.

Q2.5. The results shown could be explained by CLK acting as a transcription factor on PER.

Q2.6. In constant dark, the circadian periodicity of wild-type Drosophila is approximately 24 hours.

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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