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Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance

Nichola J. Hawkins, Hans J. Cools, Helge Sierotzki, Michael W. Shaw, Wolfgang Knogge, Steven Kelly, Diane Kelly, Bart A. Fraaije

Molecular Biology and Evolution, Volume: 31, Issue: 7, Pages: 1793 - 1802

Swansea University Authors: Steven Kelly, Diane Kelly

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DOI (Published version): 10.1093/molbev/msu134

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 previou...

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Published in: Molecular Biology and Evolution
ISSN: 0737-4038 1537-1719
Published: Oxford University Press (OUP) 2014
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URI: https://cronfa.swan.ac.uk/Record/cronfa18161
first_indexed 2014-07-25T01:30:22Z
last_indexed 2021-10-27T02:30:59Z
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spelling 2021-10-26T16:39:45.1544007 v2 18161 2014-07-24 Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance b17cebaf09b4d737b9378a3581e3de93 Steven Kelly Steven Kelly true false 5ccf81e5d5beedf32ef8d7c3d7ac6c8c Diane Kelly Diane Kelly true false 2014-07-24 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. Journal Article Molecular Biology and Evolution 31 7 1793 1802 Oxford University Press (OUP) 0737-4038 1537-1719 fungicide resistance 1 7 2014 2014-07-01 10.1093/molbev/msu134 http://dx.doi.org/10.1093/molbev/msu134 COLLEGE NANME COLLEGE CODE Swansea University 2021-10-26T16:39:45.1544007 2014-07-24T15:05:13.4055793 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Nichola J. Hawkins 1 Hans J. Cools 2 Helge Sierotzki 3 Michael W. Shaw 4 Wolfgang Knogge 5 Steven Kelly 6 Diane Kelly 7 Bart A. Fraaije 8
title Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
spellingShingle Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
Steven Kelly
Diane Kelly
title_short Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
title_full Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
title_fullStr Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
title_full_unstemmed Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
title_sort Paralog Re-Emergence: A Novel, Historically Contingent Mechanism in the Evolution of Antimicrobial Resistance
author_id_str_mv b17cebaf09b4d737b9378a3581e3de93
5ccf81e5d5beedf32ef8d7c3d7ac6c8c
author_id_fullname_str_mv b17cebaf09b4d737b9378a3581e3de93_***_Steven Kelly
5ccf81e5d5beedf32ef8d7c3d7ac6c8c_***_Diane Kelly
author Steven Kelly
Diane Kelly
author2 Nichola J. Hawkins
Hans J. Cools
Helge Sierotzki
Michael W. Shaw
Wolfgang Knogge
Steven Kelly
Diane Kelly
Bart A. Fraaije
format Journal article
container_title Molecular Biology and Evolution
container_volume 31
container_issue 7
container_start_page 1793
publishDate 2014
institution Swansea University
issn 0737-4038
1537-1719
doi_str_mv 10.1093/molbev/msu134
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://dx.doi.org/10.1093/molbev/msu134
document_store_str 0
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description 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.
published_date 2014-07-01T12:38:18Z
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