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Azole fungicide resistance: evolution on a rugged fitness landscape

Nichola Hawkins: Rothamsted Research

<div>Predicting and delaying the emergence and spread of resistance is one of the most pressing applications of evolutionary biology in medicine and agriculture. The concept of fitness landscapes, in which a lineage under selection will be driven up an adaptive peak, has previously been applied to cases of antibiotic resistance evolution. We apply the concept of fitness landscapes to the evolution of fungicide resistance in plant pathogens, and in particular to the case of target site resistance to azole fungicides in <em>Zymoseptoria tritici</em>. The azole target site <em>CYP51</em> now has over 30 reported non-synonymous mutations, combining in at least 80 different haplotypes with up to nine mutations each. Multiple mutations can have interacting effects on fungicide resistance and enzyme function, and these epistatic effects produce a rugged fitness landscape. A detailed understanding of the interactions between multiple mutations, and the trade-offs between fungicide resistance, functional constraints and fitness penalties, is needed to improve the predictability of evolutionary trajectories under different fungicide use scenarios.</div>