16 ERA-CAPs: Meiotic recombination in plants: controlling the transition of DNA double-strand breaks to genetic crossovers (MEIOREC).

Genetic variation generated through the process of homologous recombination (HR) during meiosis underpins plant breeding and efforts to deliver the rapid improvements in crops that will be required to ensure Food Security into the foreseeable future. HR is initiated by the programmed formation of DNA double-strand breaks (DSBs) by the SPO11 complex. DSBs are processed by components of the HR pathway where they are repaired as genetic crossovers (COs), which recombine the homologous parental chromosomes, or non-crossovers (NCOs), where only short stretches of DNA are exchanged. In plants most DSBs (90%+) are repaired as NCOs. This limits the genetic variation that is generated in each meiotic division. Moreover, the distribution of COs, notably in cereal crops, is localized to particular chromosomal regions. The extensive work and collaborative efforts of the MEIOREC investigators have led to significant progress in understanding the basis of these limitations and have made headway in addressing them1. Nevertheless, a full understanding of how the transition of a DSB at a particular genomic locus to yield a CO is controlled and how this can be optimized remains a major challenge. We believe that the combined expertise of MEIOREC consortium provides a real opportunity to make substantial progress in addressing this important problem.

HR is initiated by the formation of DNA double-strand breaks (DSBs) by the SPO11 complex. DSBs are processed as crossovers (COs), which recombine the homologous parental chromosomes, or non-crossovers (NCOs), where only short stretches of DNA are exchanged. In plants most DSBs are repaired as NCOs. Moreover, the distribution of COs, notably in cereal crops, is localized to particular chromosomal regions. These limitations significantly lessen the genetic variation that could be generated in each meiotic division. The extensive work of the MEIOREC investigators have led to significant progress in understanding the basis of these limitations and in addressing them. Nevertheless, a full understanding of how is controlled the transition of a DSB at a particular genomic locus to a CO and how can be optimized remains a major challenge. We aim to decipher the DSB to CO transitional molecular steps and evaluate strategies to manipulate CO formation using model species, thereby laying the foundation for subsequent translation of the most promising into crops. Our research will focus into three different stages in the control of CO formation in plants:
(i) Factors controlling DSB formation: We will determine their minimum requirements, evaluate a MTOPVIB-CRISPR system, the use of a suppression cassette (dCas9) and multiple short guide RNAs of the CO suppressor genes to enhance CO frequency.
(ii) DSB processing, stable joint molecule formation and CO resolution: We will address how early steps in DSB processing and recombinase loading are linked and how this impacts on the CO/non-CO decision by analysing the role of the MRN complex and COM1 in the efficient removal of SPO11.
(iii) Relationship of chromosome remodelling and CO formation: We will analyse the influence of posttranslational modifications on chromosome axis in relation to ensuring the bias towards inter-homologue recombination.

Ensuring Food Security over the forthcoming years is one of the main challenges for society. Different factors like population growth and climate change will increase the necessity of sustained improvements in food production (by 2050 it is predicted that food production will have to be increased by at least 50%). Crop breeding would have to improve to deliver the required yields. Molecular plant breeding has transformed the available options for plant breeders in recent years. Nonetheless, crop breeding is highly dependent of meiotic recombination to generate genetic variation through the formation of crossovers (COs). Plant chromosomes have a limited frequency of COs (1-3 per chromosome pair) and their distribution is not uniform across the genome. For instance, it has estimated that 30-50% of the genes in cereal species, such as barley, maize and wheat, rarely recombine, limiting the genetic variation available to plant breeders. The relevance and timeliness of the MEIOREC research programme arises through a clear objective to address these limitations. The existing links between partners in MEIOREC and plant breeding companies through current national and international programmes will ensure an optimal route to achieve impact with our results, which will facilitate a potential commercial or industrial application.
MEIOREC is creating a consortium of international leading research groups with different expertise to develop new molecular approaches to address essential questions in plant meiosis research in order to control plant meiotic recombination for future plant breeding technologies. MEIOREC will play a significant part in strengthening the European-USA plant meiosis research. The outputs of this consortium will develop new approaches to harness the genetic variation in plants and use in plant breeding to improve crop species and provide food security.