Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance

Hawkins, N. J., Cools, H. J., Sierotski, H., Shaw, M. W., Knogge, W., Kelly, S. L., Kelly, D. E. and Fraaije, B. A. (2014) Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance. Molecular Biology and Evolution, 31 (7). pp. 1793-1802. ISSN 1537-1719 doi: 10.1093/molbev/msu134

Abstract/Summary

Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/37039
Identification Number/DOI	10.1093/molbev/msu134
Refereed	Yes
Divisions	Life Sciences > School of Agriculture, Policy and Development > Department of Crop Science
Uncontrolled Keywords	standing variation gene duplication resistance fungicides triazoles Rhynchosporium
Publisher	Oxford University Press
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