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← Theoretical A

Q27 — Beta-Lactamase Mutational Trajectories and Epistasis

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

Five mutations in beta-lactamase can significantly affect its ability to degrade third-generation antibiotics like cefotaxime: Mut1, Mut2, Mut3, Mut4, Mut5. Since they can appear in any order there are 5! (=120) potential trajectories of resistance development. However, only 18 of them are evolutionarily accessible. The term “evolutionarily accessible” refers to the ability of a particular mutational pathway to produce an advantageous phenotype during the evolution. Implications from this simple model could be used to understand the evolution of more complex traits.

Graph of the ten most probable mutational trajectories from wild-type beta-lactamase to an improved variant, with enzyme efficiency values labeled at each node and colored arrows for each of the five mutations, alongside a cumulative probability plot for all 18 accessible trajectories. Figure 1. A Graph showing the ten most probable trajectories leading from wild-type beta-lactamase (BL(WT)) to an improved version (BL), the efficiency of each phenotype indicated on the node. Colored arrows represent the five potential mutations. B The cumulative probability of each of the 18 possible trajectories.*

On your answer sheet, indicate “T” for true statements and “F” for false ones.

A. Some mutations require additional mutations to have a significant effect.
B. The trajectories 1-18 (Figure 1B) are arranged based on the increasing probability of occurrence.
C. A mutation's effect on fitness influences the probability of this specific mutation occurring.
D. The final fitness of the trajectory is the primary factor affecting the evolutionary accessibility of the trajectory.

Question reproduced from IBO 2024, Theoretical Exam Part A, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)