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

A - Papers appearing in refereed journals

Hawkins, N. J., Cools, H. J., Sierotzki, 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.

AuthorsHawkins, N. J., Cools, H. J., Sierotzki, H., Shaw, M. W., Knogge, W., Kelly, S. L., Kelly, D. E. and Fraaije, B. A.
Abstract

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.

Keywordsstanding variation; gene duplication; resistance; fungicides; triazoles; Rhynchosporium
Year of Publication2014
JournalMolecular Biology And Evolution
Journal citation31 (7), pp. 1793-1802
Digital Object Identifier (DOI)doi:10.1093/molbev/msu134
Open accessPublished as ‘gold’ (paid) open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeDelivering Sustainable Systems (SS) [ISPG]
Wheat
The Rothamsted Long-Term Experiments including Sample Archive and e-RA database [2012-2017]
BBSRC CASE studentship: Recent evolution of Rhynchosporium secalis populations in response to selection by fungicides
Investigation of resistance to Succinate Dehydrogenase Inhibitors in plant pathogenic fungi
Understanding pesticide resistance and developing sustainable crop protection strategies
Publisher's version
Output statusPublished
Publication dates
Online14 Apr 2014
PublisherOxford University Press (OUP) Oxford
Oxford University Press (OUP)
Copyright licenseCC BY
ISSN0737-4038

Permalink - https://repository.rothamsted.ac.uk/item/8qy5q/paralog-re-emergence-a-novel-historically-contingent-mechanism-in-the-evolution-of-antimicrobial-resistance

10 total views
31 total downloads
1 views this month
4 downloads this month
Download files as zip