Accelerating plant breeding by modulating recombination.

Lead Research Organisation: Aberystwyth University
Department Name: IBERS

Abstract

To meet expected demand, the world will need to produce 50 percent more food in 2050 than it did in 2012. While similar growth rates have been achieved in the past, future growth faces the additional pressure of climate change and the need for reduced chemical inputs. Sustainably enhancing agricultural production is therefore a major challenge facing the sector.

A valuable source of traits for disease resistance and abiotic stress tolerance resides in thousands of living wild crop relatives. Accessing these traits for plant breeding, however, is limited by "genetic drag", where low levels of genetic exchange (recombination) means that both desirable and undesirable "wild traits" are introduced and can be difficult to separate. Boosting recombination overcomes genetic drag allowing access to diverse germplasm, as well as increasing the efficiency of traditional breeding programs, helping generate the new combinations of traits required for crop improvement in fewer generations.

Recombination can be increased in plants 8-fold by knocking out anti-recombinase genes. However, establishing multigene knockouts in every breeding program is not practical, approaches used to generate mutants may preclude cultivation in tightly (GMO) regulated environments and the mutations introduced can reduce fertility, so wild type alleles must be restored prior to cultivation. Transiently increasing recombination without modification of the recombination machinery itself would solve these problems.

To achieve this goal, we will use high-throughput screening assays to identify small molecule inhibitors of key recombination suppressing proteins that can be used to transiently boost recombination in a wide variety of crop species. To identify inhibitors, we will design targeted compound libraries for screening based on molecules identified in large biomedical drug screens that inhibit human orthologs of our target proteins. In addition, virtual screening of large compound libraries will be used to identify further compounds of interest for testing. We will also identify and/or develop plant versions of peptides known to boost recombination in mammalian systems. Once identified, delivery of recombination boosting small-molecules will be optimised for use in crops. This will be initially be undertaken in Brassica and barley, covering a dicot crop closely related to the model plant Arabidopsis, and a key grain crop, both with well-developed cytological tools.

Another route for crop development is to incorporate the traits and diversity of two genomes into a single individual - known as allopolyploidy. Allopolyploid plants are common in agriculture (e.g. wheat and cotton) as their fixed hybrid nature usually results in improved agricultural traits. Despite their potential, previous attempts to generate new allopolyploid crops have failed as they tend to have genomic instability and low fertility due to recombination between the two sub-genomes. Two interacting genes have recently been implicated in suppressing this inter-genomic recombination and we will assess the potential to use/modify these genes, and others in the same pathway, to engineer a stable meiosis in new allopolyploids. If successful we will use this approach to generate new genetically stable allopolyploid Brassica and pasture grasses.

This multi-disciplinary project, draws on expertise of the Fellow and Project Partners in molecular plant science, phenomics, plant breeding, polyploidy, medicinal chemistry and biochemistry to modify recombination in plants for accelerated plant breeding, helping to develop the high nutrition, climate ready and disease resistant crops needed to meet future food needs. The final three years of the project will involve product development in collaboration with breeding companies to optimise delivery and effectiveness during plant breeding and establishment of a start-up company to commercialise the product(s) developed.

Planned Impact

To meet expected demand, the world will need to produce 50 percent more food in 2050 than it did in 2012. While similar growth rates have been achieved in the past, future growth faces the additional pressure of climate change and the need for reduced chemical inputs. Sustainably enhancing agricultural production is therefore a major challenge facing the sector.

A valuable source of traits for disease resistance and abiotic stress tolerance resides in thousands of living wild crop relatives. Accessing these traits for plant breeding, however, is limited by "genetic drag", where low levels of genetic exchange (recombination) means that both desirable and undesirable "wild traits" are introduced and can be difficult to separate. Boosting recombination overcomes genetic drag allowing access to diverse germplasm, as well as increasing the efficiency of traditional breeding programs, helping generate the new combinations of traits required for crop improvement in fewer generations.

Recombination can be increased in plants 8-fold by knocking out anti-recombinase genes. However, establishing multigene knockouts in every breeding program is not practical, approaches used to generate mutants may preclude cultivation in tightly (GMO) regulated environments and the mutations introduced can reduce fertility, so wild type alleles must be restored prior to cultivation. Transiently increasing recombination without modification of the recombination machinery itself would solve these problems.

To achieve this goal, we will use high-throughput screening assays to identify small molecule inhibitors of key recombination suppressing proteins that can be used to transiently boost recombination in a wide variety of crop species. To identify inhibitors, we will design targeted compound libraries for screening based on molecules identified in large biomedical drug screens that inhibit human orthologs of our target proteins. In addition, virtual screening of large compound libraries will be used to identify further compounds of interest for testing. We will also identify and/or develop plant versions of peptides known to boost recombination in mammalian systems. Once identified, delivery of recombination boosting small-molecules will be optimised for use in crops. This will be initially be undertaken in Brassica and barley, covering a dicot crop closely related to the model plant Arabidopsis, and a key grain crop, both with well-developed cytological tools.

Another route for crop development is to incorporate the traits and diversity of two genomes into a single individual - known as allopolyploidy. Allopolyploid plants are common in agriculture (e.g. wheat and cotton) as their fixed hybrid nature usually results in improved agricultural traits. Despite their potential, previous attempts to generate new allopolyploid crops have failed as they tend to have genomic instability and low fertility due to recombination between the two sub-genomes. Two interacting genes have recently been implicated in suppressing this inter-genomic recombination and we will assess the potential to use/modify these genes, and others in the same pathway, to engineer a stable meiosis in new allopolyploids. If successful we will use this approach to generate new genetically stable allopolyploid Brassica and pasture grasses.

This multi-disciplinary project, draws on expertise of the Fellow and Project Partners in molecular plant science, phenomics, plant breeding, polyploidy, medicinal chemistry and biochemistry to modify recombination in plants for accelerated plant breeding, helping to develop the high nutrition, climate ready and disease resistant crops needed to meet future food needs. The final three years of the project will involve product development in collaboration with breeding companies to optimise delivery and effectiveness during plant breeding and establishment of a start-up company to commercialise the product(s) developed.

Publications

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Crismani W (2021) Crossover interference: Just ZYP it. in Proceedings of the National Academy of Sciences of the United States of America

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Lloyd A (2023) Crossover patterning in plants. in Plant reproduction

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Nibau C (2022) Meiosis in allopolyploid Arabidopsis suecica. in The Plant journal : for cell and molecular biology

 
Description Key Findings to Date

Synthesis of literature on crossover patterning in plants:
We have described the molecular pathways and genomic features that influence crossover patterning in plants.

Characterisation of meiosis in A. suecica:
We have characterised meiosis in the model allopolyploid Arabidopsis suecica. This emerging model is a powerful tool for dissecting the molecular pathways that determine the "stringency" of meiotic recombination i.e. what limits gene-flow in both wild populations and (pre-)breeding programmes? Our characterisation sets the base from which future studies looking to dissect the relevant molecular pathways involved (e.g. using CRISPR mutants, forward genetics, etc) can be compared.

The mismatch repair pathway does not suppress homoeologous recombination in A. suecica:
The mismatch repair pathway has been suggested to limit genetic recombination between divergent sequences. We have generated msh2 CRISPR mutants in Arabidopsis suecica and characterised meiosis in these lines. We have demonstrated that, contrary to previous hypotheses, loss of MSH2 does not result in increased recombination between divergent sequences - thus targeting this gene is unlikely to be useful for promoting wild trait introgression in plant breeding programmes.
Exploitation Route These results will be taken forward by ourselves and by other researchers interested plant meiosis. It is of particular relevance to plant (pre-)breeders and may impact decisions made about how best to introgress useful traits from crop wild relatives into cultivated varieties.
Sectors Agriculture, Food and Drink

 
Description Research Grant: PolyPaints - Developing Oligo Paints for Arabidopsis
Amount £35,855 (GBP)
Funding ID RGS\R1\231323 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2023 
End 03/2024
 
Title Meiosis in Allopolyploid Arabidopsis suecica 
Description Cytological images for Nibau et al, Meiosis in Allopolyploid Arabidopsis suecica, 2022, The Plant Journal. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact Publication of research article in The Plant Journal. DOI: 10.1111/tpj.15879 
URL https://pure.aber.ac.uk/portal/en/datasets/meiosis-in-allopolyploid-arabidopsis-suecica(107b344b-d0d...
 
Description Educational Video for Schools - Part of the Welsh Government Office for Science's contribution to 2022 British Science Week 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact I was invited to submit one of 5, 20-30 minute videos put together by the Welsh Government Office for Science for their contribution to 2022 British Science Week. These videos were from scientists working in Wales, talking about their research with a target audience of Year 10 and Year 11 pupils, i.e. the GCSE years. The films are put up on the Welsh Government's Hwb education platform, from the beginning of BSW on 11th March 2022, to allow everyone to access the material., including teachers, who might want to build a given film into a lesson plan. They will likely remain online as a resource for several years.

The video discussed our research and how it fits into that of the wider institute's goal of addressing sustainable agriculture and food production.
Year(s) Of Engagement Activity 2022
 
Description Interview for "The Science Show" on ABC Radio National (Australia) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I was interveiwed on ABC Radio National's The Science Show (Australia) for an episode on international recognition for Australian Scientists. In the interview I discussed our research programme at Aberystwyth University and the plans for research to be undertaken under my UKRI Future Leaders Fellowship. This show was broadcast on the 7th of November 2020 and continues to be available as a podcast.

The Science Show is the flagship science program on Australia's national broadcaster, ABC Radio National. ABC RN has a very wide national audience (~650,000 weekly listeners). The Science Show also has a very wide international podcast audience e.g it is in the Top 10 science podcasts in Australia, top 100 science podcasts in the USA and in the top 50 natural science podcasts in the UK (metrics from chartable.com).
Year(s) Of Engagement Activity 2020
URL https://www.abc.net.au/radionational/programs/scienceshow/australian-andrew-lloyd-awarded-uk-future-...
 
Description Interview for BBC Wales Science Cafe 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Associated with the international year of Fruit & Vegetables I gave an interview on BBC Wales' Science Cafe program talking about the research being undertaken in my UKRI Future Leaders Fellowship "Accelerating Plant Breeding by Modulating Recombination", and the importance of sustainable approaches to crop development.

This interview had a wide general public audience (BBC Wales has a weekly audience of around 350,000) and has led to additional opportunities to present my research to policy makers (e.g. ) and the general public (e.g. British Science Week 2022).
Year(s) Of Engagement Activity 2021
URL https://www.bbc.co.uk/programmes/m000qwwx
 
Description Virtual Panel Discussion on Early Career Researcher Mobility and Support for Welsh Government 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact I took part in a virtual panel, chaired by the Chief Scientific Adviser for Wales, Professor Peter Halligan on Thursday 4th March. The audience was members of the Welsh Senedd, policy makers / public servants. The theme was how Welsh Government programmes have supported researchers early on their careers with mobility. I discussed my experiences being involved in several programs supported by the Welsh Government including my Sêr Cymru fellowship (2018-2021) and participation in "Welsh Crucible". I also discussed my current research and plans following being awarded a Future Leaders Fellowship. The panel then took part in a Q&A session fielding questions from the audience.
Year(s) Of Engagement Activity 2021