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New evolutionary mechanism in fungicide resistance

New mechanism in azole resistance evolution

Analysis of samples from a 160-year-old experiment at Rothamsted Research reveals the re-emergence of an ancient gene due to modern agricultural practices.

Pests and diseases can develop resistance to chemicals used for crop protection, and this poses a major challenge for future food security, as antibiotic resistance poses a major challenge in medicine. Rothamsted Research scientists, who receive strategic funding from the BBSRC, investigated shifts in sensitivity to the azoles, an important class of fungicides, in the barley leaf blotch pathogen Rhynchosporium commune. They used infected barley leaf samples from the Hoosfield long-term experiment spanning 160 years and tested them for the presence of fungal CYP51 genes, which encode the sterol demethylase enzymes targeted by azole fungicides. They have been able to demonstrate for the first time that CYP51A, an ancient gene pre-existing at low frequency in the Rhynchosporium commune population, re-emerged after being selected by azole fungicides in the late 20th century.  Strains of Rhynchosporium commune that have the CYP51A gene are more able to cope with azole fungicide treatments and therefore survive better. Generation after generation, as these strains have higher survival rates, the frequency of the gene in the population increases. The study is published in the journal Molecular Biology and Evolution.

Understanding the mechanisms that contribute to the development of resistance by a pest to a chemical agent is essential in order to develop appropriate pest management strategies and protect future crop yields. Evolution by natural selection is the underlying driver for the development of resistance, but each species may respond differently. Therefore more detailed understanding of the evolution of resistance not only contributes towards practical solutions but also advances the wider field of evolutionary biology.

Dr Nichola Hawkins, the Rothamsted scientist who carried out this research during a BBSRC CASE PhD studentship, said: “We are very excited by our findings as this is a novel mechanism for the evolution of resistance. A long-standing question in evolutionary biology is whether evolution is inherently predictable, and constrained to follow only a few possible paths, or whether a range of outcomes are possible depending on various steps along the way. This study shows a rather unexpected pathway. The CYP51A gene originated around 400 million years ago, when clubmosses and amphibians were first taking to the land. Some species have retained the CYP51A gene, others have lost it over time. Rhynchosporium commune had almost lost CYP51A over the last 4000 years, but the use of synthetic fungicides in the late 20th Century provided a new selective pressure for CYP51A to spread back through the population. If it had already completely lost CYP51A by the time azoles were introduced, this adaptive pathway would not have been available.”

Dr Bart Fraaije, lead scientist of this work at Rothamsted, said: “This work is very significant. Some fungal genomes have multiple copies of CYP51- the usual CYP51B plus the extra CYP51A- making those species naturally less sensitive to azoles. CYP51A can be over-expressed, as in citrus green mould (Penicillium digitatum), and/or carry mutations, as in the respiratory fungal infection,Aspergillosis (Aspergillus fumigatus), further increasing azole resistance. Here we report the first case of variation in the presence or absence of CYP51A within a species. Older strains of Rhynchosporium commune seemed to lack CYP51A, but our analyses show it was present at low levels and then selected by fungicides. Our work shows that pre-existing differences (“standing variation”) in the fungal population can be an important risk factor for fungicide resistance.

“One has to greatly admire the foresight of Rothamsted’s founders, Sir John Lawes and Sir Henry Gilbert, in keeping samples, as this means we can analyse samples from the 19th Century with 21st-Century DNA sequencing technology. Here we used one of Rothamsted’s world renowned classical experiments, set up in 1852, to address questions relating to a pressing current issue of drug and pesticide resistance. Further work is required to investigate CYP51 evolution in other fungal species in the Rothamsted archives,” Dr Fraaije added.

Publication

Notes to Editors

Publication:

Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance Mol Biol Evol 1 July 2014: 1793-1802.

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About Rothamsted Research

We are the longest running agricultural research station in the world, providing cutting-edge science and innovation for over 170 years. Our mission is to deliver the knowledge and new practices to increase crop productivity and quality and to develop environmentally sustainable solutions for food and energy production.

Our strength lies in the integrated, multidisciplinary approach to research in plant, insect and soil science.

Rothamsted Research is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC). In 2013-2014 Rothamsted Researched received a total of £32.9M from the BBSRC.

About BBSRC

The Biotechnology and Biological Sciences Research Council (BBSRC) invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by Government, BBSRC invested over £509M in world-class bioscience in 2014-15. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

For more information about BBSRC, our science and our impact see: http://www.bbsrc.ac.uk

For more information about BBSRC strategically funded institutes see: http://www.bbsrc.ac.uk/institutes