Award details

Resistance: DNA methylation and the evolution of pesticide-resistance genes in aphids

Reference	BB/R009481/1
Principal Investigator / Supervisor	Professor Saskia Hogenhout
Co-Investigators / Co-Supervisors	Dr David Swarbreck, Professor Cock van Oosterhout
Institution	John Innes Centre
Department	Crop Genetics
Funding type	Research
Value (£)	962,887
Status	Completed
Type	Research Grant
Start date	01/04/2018
End date	30/09/2021
Duration	42 months

Abstract

The green peach aphid (GPA) Myzus persicae has evolved resistance to 71 chemicals in 50 years, and it has become a model to study the evolution of "pesticide-breaking". In a former BBSRC project, we discovered that DNA methylation by two genes (DNMT3A and 3B) enables GPA to up- and down-regulate genes associated with resistance. In this proposal, we aim study the entire gene networks affected by de novo DNA methylation mediated by DNMT3A and 3B. We also analyse the evolutionary forces that generate and shape the DNA variation underpinning the existing genetic adaptations in an agricultural setting. Aim 1 is to characterize the genes that depend on DNMT3A/B for differential expression (DE) upon GPA host change (Aim 1.1) and pesticide treatment (Aim 1.2). We will isolate and sequence RNA from aphids with and without host transfer / insecticide exposure to identified DE genes. We will then conduct gene-specific bisulphite sequence of DE genes to examine the link between gene body methylation and DE (Aim 1.3). Aim 2 investigates how pesticide treatment and DNMT3A/B affect gene expression of two specialist aphid species. We will test how the knock down of DNMT3A/B affects GPA and two specialist aphid species to adjust to new plant hosts and pesticides. We will also identify the genes that depend on DNMT3A/B regulation in specialist and generalist aphids. Aim 3 elucidates the evolution of genes in the DNMT3A/B pathway involved in response to plant host change and pesticides in GPA, and other (generalist and specialist) pest insects. Aim 3.1 examines the level of genome streamlining, the number of lineage-specific genes in multigene families, and number tandem-duplications of detoxifying genes, testing the hypothesis that these features are associated to rapid pesticide-breaking. Aim 3.2 will identify genes and genomic areas in GPA that are under positive selection across world populations with known history of insecticide usage (in collaboration with Syngenta).

Summary

Most insect species are specialist parasites that have adapted to colonize one or a few closely related plant species. Circa 10% of all insect herbivores are generalist ("polyphagous"), and these are often the most noxious pests, having evolved resistance to many pesticides. Generalist insects are prone to such "pesticide-breaking" because by being exposed to a wide range of hosts, they have already evolved resistance to many different plant chemicals. Worryingly, many of these phytochemicals have been used to derive pesticides, and this makes such generalist insects pre-adapted to pesticide-breaking. The green peach aphid (GPA) Myzus persicae can colonize over 400 different plant species, and it has evolved resistance or tolerance to 71 chemicals in 50 years. GPA has become a model to understand how "pesticide-breaking" has evolved. In a former BBSRC funded project, we discovered the molecular mechanism underpinning the insect's remarkable adaptive potential; DNA methylation by two genes (DNMT3A and 3B) enables GPA to adjust to diverse plant species and overcome pesticide toxicity without genetic modification. Genetically identical clones can adjust to a new host plant and show pesticide resistance within hours or days after exposure, and furthermore, their (genetically identical) offspring becomes increasingly well-adjusted. We have shown that the expression of detoxification genes is controlled by DNA methylation (which is an epigenetic process). We also showed that when DNMT3A/B methylation is knocked-down, that the aphids can no longer adjust. We also know that different genes are being up- or down-regulated by DNMT3A/B methylation depending on the host plant or pesticide being encountered. Building on this knowledge, our new proposal has two principal objectives: 1) Identify and describe the entire gene networks affected by de novo DNA methylation mediated by DNMT3A/B. This is important because these are the genes that enable the aphid to detect and respond to the pesticide, and hence, this will help the development of pesticides against novel insect targets. Our Project Partner Syngenta, and others, will thus be helped in their development of such pesticides. 2) Understand the evolutionary forces that generate and shape the DNA variation underpinning the genetic variation in these "resistance genes" in the DNMT3A/B pathway. This is important because the 50 years of pesticide usage will have left a decipherable signature in the genome of the aphids (and other pest insects). By studying this signature, we can optimise pest insect control strategies. The hypotheses are: 1) GPA possesses genes that help the insect to detect the novel host plant / pesticides, which instigates DNMT3A/B upregulation. 2) The DNMT3A/B methylated genes enable the insect to detoxify these chemicals. 3) Generalist aphids (e.g., GPA) display a larger change in DNMT3A/B expression levels upon host switch and pesticide exposure than specialist aphids (such as the cabbage aphid Brevicoryne brassicae, and the English grain aphid Sitobion avenae). 4) Co-regulatory networks affected by DNMT3A/B are more extensive for generalist than specialist aphids. 5) Generalist insect pests (including herbivores, animal and human insect pests) show genome streamlining, lineage-specific gene families and gene duplication that is distinctive from specialist pest insects. 6) The historic use of pesticide treatment will have impacted the 5 evolutionary forces (mutation, recombination, gene flow, genetic drift and natural selection), which has shaped the genomic variation in GPA in populations across the world. In collaboration with our Project Partner Syngenta, we have designed three exciting experiments that test these hypotheses. We believe the knowledge generated by this research is likely to uncover new targets for insect control, and will help to optimise species-specific insect control strategies, and hence secure sustainable agriculture.

Impact Summary

This proposal is for the BBSRC highlight call 'Understanding the challenge of resistance in agriculture' in which the green peach aphid (GPA, Myzus persicae) is specifically mentioned. This proposal responds to all aims in the call. Here we detail who will benefit from our proposed research and explain how, focusing on the specific aims from the BBSRC highlight call: 1. "Using new scientific approaches to address practical problems for agriculture or resistance to pesticides." and "Focusing on the molecular mechanisms of resistance, its evolutionary drivers and the ecological processes involved in the emergence and spread." - Our previous BBSRC grant (BB/L002108/1: "Functional Genomics of Aphid Adaptation to Plant Species") identified DNMT3A/B as an important molecular mechanism controlling the regulation of genes that enable GPA to parasitise new host plants and overcome pesticide toxicity. Building on this breakthrough, we now wish to dissect the entire gene pathway enabling GPA to detect and adapt to pesticides. Beneficiaries: We believe this will help industry, such as our project partner Syngenta, to identifying new potential targets for pesticide development. In turn, this will aid agriculture and food security. 2. "Promoting collaboration between researchers with existing interests in resistance and others with wider relevant expertise in underpinning science." - The proposal involves researchers interested in molecular aspects of plant-insect interactions (Hogenhout. JIC), genomics / bioinformatics (Swarbreck. EI), and evolution (Van Oosterhout, UEA), and Syngenta, Jealott's Hill (Firth and colleagues). The integration of functional genetics and genomics with evolutionary theory enhances the proposed research project. We will be using population genetic theory to understand the processes that occur during the evolution of insecticide resistance in the field, resequencing the genomes of ~100 GPA individuals exposed to pesticides across the globe. Beneficiaries: The research is of direct relevance to Syngenta, who have committed to support this proposal with a >10% contribution, and others. Besides this financial contribution, the project will benefit significantly from the knowledge of Syngenta about the previous usage of pesticides in locations that will be sampled for GPA to resequence. We believe that the knowledge generated will improve pest insect control strategies, promoting more sustainable usage of pesticides in agriculture, thereby helping long-term food security. 3. "Stimulating innovative research to understand resistance and inform interventions for enhancing effectiveness of existing products and optimizing the use of new ones" - The neonicotinoid TMX has been particularly effective at control of GPA for many years, but "pesticide breaking" appears to be an evolutionary inevitability, especially for generalist pests such as GPA. By using a comparative phylogenomic approach, this proposal investigates how GPA and a wide range of other pest insects have evolved resistance to pesticides in the agricultural setting. Beneficiaries: The proposed research will aid Syngenta as well as other strategic research projects of the Hogenhout lab, such as the identification of plant resistance to GPA (funded by BBSRC-LINK and iCASE projects with the sugar beet seed breeding company SESVanderHave), development of control methods for the notorious insect pest, the tobacco whitefly Bemisia tabaci (iCASE project with Oxitec), and establishing global networks on vector-borne diseases (funded by the UK-US partnership award and GCRF network with East Africa). 4. "Raising the profile amongst the broader research community of the impact of resistance on agriculture and the scientific challenges it presents." - Here, we plan to engage to broader research community and the public by setting up the OpenINSECTVector website and engaging with the general public in a Citizen Science (see Pathways to Impact).

Committee	Research Committee B (Plants, microbes, food & sustainability)
Research Topics	Crop Science, Plant Science
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	Industrial Partnership Award (IPA)

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