
NSF Org: |
IOS Division Of Integrative Organismal Systems |
Recipient: |
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Initial Amendment Date: | September 8, 2016 |
Latest Amendment Date: | June 16, 2021 |
Award Number: | 1546792 |
Award Instrument: | Continuing Grant |
Program Manager: |
Diane Jofuku Okamuro
dokamuro@nsf.gov (703)292-4508 IOS Division Of Integrative Organismal Systems BIO Directorate for Biological Sciences |
Start Date: | September 15, 2016 |
End Date: | August 31, 2022 (Estimated) |
Total Intended Award Amount: | $4,044,895.00 |
Total Awarded Amount to Date: | $4,044,895.00 |
Funds Obligated to Date: |
FY 2017 = $1,031,682.00 FY 2018 = $990,333.00 |
History of Investigator: |
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Recipient Sponsored Research Office: |
341 PINE TREE RD ITHACA NY US 14850-2820 (607)255-5014 |
Sponsor Congressional District: |
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Primary Place of Performance: |
401 Bradfield Hall Dryden NY US 14853-7202 |
Primary Place of
Performance Congressional District: |
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Unique Entity Identifier (UEI): |
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Parent UEI: |
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NSF Program(s): | Plant Genome Research Project |
Primary Program Source: |
01001718DB NSF RESEARCH & RELATED ACTIVIT 01001819DB NSF RESEARCH & RELATED ACTIVIT |
Program Reference Code(s): |
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Program Element Code(s): |
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Award Agency Code: | 4900 |
Fund Agency Code: | 4900 |
Assistance Listing Number(s): | 47.074 |
ABSTRACT
Meiotic recombination is a process in which two parental chromosomes, one from the father and the other one from the mother, exchange parts to give rise to the next generation. This process creates new genetic variation in the progeny, which facilitates adaptation to new environments and purges detrimental mutations from genomes. Thus, meiotic recombination is one of the main forces behind evolution. In addition, it is utilized as an unparalleled instrument of plant and animal breeding. In stark contrast to its importance, surprisingly little is known about mechanisms controlling recombination, particularly in plants. Mechanisms of recombination appear to be different in each major group of eukaryotes and also highly dependent on genome size and complexity. Recombination events are not evenly distributed throughout the genome but predominantly take place at distinct sites called recombination "hotspots". This project seeks to understand why and how specific sites in the genome become recombination hotspots in maize. In addition to contributing significant new insight into an important biological process, the information generated will be useful to breeders who are continuously looking for new ways to increase recombination for more efficient breeding of crop plants. With regard to outreach and training, the project will develop a Science Undergraduate Minority Mentoring Internship and Training (SUMMIT) program which will provide yearly 10-week research training internships for minority undergraduate students.
The goal of this project is to illuminate the mechanisms controlling distribution of recombination events in maize. This work capitalizes on the recent success in generating a high-resolution map of double-strand-breaks (DSBs), which initiate meiotic recombination, and a high-resolution map of crossover (COs) in maize. The plan is to elucidate why recombination takes place in specific sites in the genome and understand how the locations of these sites are affected by genetic and epigenetic factors. The molecular mechanisms of hotspot recognition will be unraveled by searching for proteins interacting with the newly discovered DNA sequence motif present at recombination hotspots, examining the role of DNA and histone methylation on hotspot activity, and investigating the link between DSB hotspot presence and chromatin openness. In addition, mechanisms that prevent formation of COs in heterochromatin will be elucidated. This work will further the understanding of how recombination is controlled in plants and how it affects the structure of large and complex plant genomes. All project outcomes will be made accessible to the public. Data generated in this project will be made available to the public through the project website (www.rec-hotspots.org) and through the appropriate long-term repositories such as MaizeGDB and the NCBI's SRA. Genetic resources will be made available through the Maize Genetics Cooperation Stock Center.
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PROJECT OUTCOMES REPORT
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This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
The goal of this project was to illuminate the mechanisms controlling distribution of recombination events in maize, a model species as well as a major crop. Meiotic recombination is a process in which two parental chromosomes, one from the father and the other one from the mother, exchange parts during sexual reproduction. Recombination creates new genetic variation in the progeny, which facilitates adaptation to new environments and purges detrimental mutations from genomes and populations. Thus, meiotic recombination is one of the main forces behind species evolution. In addition, it is utilized as an unparalleled instrument of plant and animal breeding. However, despite their importance, recombination events are not evenly distributed along chromosomes. In plants with large and complex genomes, such maize and the majority of other crops, they are predominantly located at chromosome ends, leaving large regions in the middle of chromosomes devoid of recombination. Such distribution pattern creates major impediment to breeding, since the recombination-poor chromosome segments contain a significant fraction of genes.
This project sought to elucidate why recombination takes place in specific sites in the genome and understand how the locations of these sites are affected by genetic and epigenetic factors. With artificial intelligence approaches, we found that the genome sites where meiotic recombination takes place exhibit specific chromatin characteristics that are distinct from those of the genome at large. Interestingly, different sets of chromatin features promote the initiation of meiotic recombination, which occurs by programmed formation of breaks in DNA, versus the repair of these breaks to form reciprocal exchanges of chromosome segment called crossovers. We also developed a method to track the progression of crossover intermediates and discovered that the patterns of crossover distribution are decided at multiple steps during the progression of the recombination pathway. We found that DNA methylation is the key factor controlling whether meiotic DNA breaks are repaired as crossovers. Reducing genome-wide DNA methylation levels opens up to crossover formation chromosome regions that are normally crossover deprived. Furthermore, we developed a computer algorithm that can very precisely identify crossover sites by taking into account the local DNA methylation levels and presence of nucleosomes. This algorithm performs equally well across different plant species, suggesting conservation of characteristics that affect crossover distribution. Finally, we also found that although the distribution of crossovers produced in males and females is similar at the chromosome-wide scale, there are several differences between the sexes in microscale.
Understanding the mechanism controlling the distribution of recombination events will facilitate development of methods to increase recombination in the low-recombination regions of chromosomes. Such methods will allow breeders to create novel combinations of genes that are located in these regions, and help them produce superior crop varieties. To facilitate translation of results of this project into technologies useful for plant breeding, we formed a strategic partnership with Meiogenix Inc, a biotech startup focused on developing tools for targeting recombination to specific chromosome regions in yeast and plants. We collaborated with Meiogenix include in their technology portfolio methods to boost crossovers by altering DNA methylation levels. As another avenue of translating the knowledge on recombination into plant breeding practice, we conducted a simulation study to examine how altering CO patterns can affect selection gain. Within the scope of the projects, we operated a Science Undergraduate Minority Mentoring Internship and Training (SUMMIT) program, which each year sponsored four 10-week internships for undergraduate students from groups underrepresented in biological sciences.
Last Modified: 11/03/2022
Modified by: Wojciech P Pawlowski
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