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Molecular and Evolutionary Genetics of Meiotic Drive

Award Number: R01GM074737
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/16/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Molecular and Evolutionary Genetics of Meiotic Drive - Project Summary/Abstract Mendel's first law describes how the two alleles in a heterozygous individual have equal chances of being transmitted to its progeny. Decades of work have revealed that different types of selfish DNAs can parasitize host species and subvert Mendel's first law to increase their transmission to offspring and their frequency in populations. These selfish DNAs are deleterious as they can reduce fertility and distort allele frequencies of host genes in populations. The asymmetric meiosis found in the females of many species including humans is particularly prone to attack by selfish DNAs because only one meiotic product forms an egg while the remainder become polar bodies. Meiotic drivers exploit this asymmetry by biasing their transmission to the egg. Moderate-strength meiotic drivers that bias their transmission by a few percent may be prevalent in populations but have been challenging to identify due to the necessity of distinguishing them from viability effects. This proposal will determine the identity and mechanism of a recently discovered candidate meiotic driver discovered in a natural population of the fruit fly Drosophila melanogaster that causes an approximately 4% deviation from normal Mendelian segregation. This candidate maps broadly to a centromeric region, leading to the working hypothesis that it corresponds to a variant in heterochromatic repetitive DNA. Novel methods will first be used to track the genotype and state of development of individuals throughout the life cycle, from meiosis in their mothers through adulthood, in order to determine the mechanism of meiotic drive. Heterochromatic regions have long been considered inaccessible to conventional genetic mapping approaches due to their complete suppression of meiotic recombination. A new approach is developed here to generate recombinants across the centromeric region in order to perform a high-resolution association study of repeat type and abundance relative to meiotic drive. Importantly, this approach does not require genome assembly across the centromere. We will also apply both short-read and long-read sequencing technologies to identify candidate sequences responsible for drive. Following these mapping and sequencing approaches, experimental manipulation will be used to test and confirm identity of the meiotic driver. Evolutionary theory predicts that meiotic drive will vary in degree between populations. This proposal will investigate the magnitude of drive in both related and unrelated populations, and then map and identify major-effect modifier alleles. Other candidate meiotic drivers will also be characterized by the approaches developed here. This proposal will provide an unprecedented level of information about the identity and mechanism of meiotic drivers that are segregating in natural populations, and provide a framework and series of methods that can be applied to other types of non-Mendelian transmission in a wide range of organisms.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	16	6/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $320,587 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	16	12/22/2021	NON-COMPETING CONTINUATION	$288,527
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	16	7/27/2022	NON-COMPETING CONTINUATION	$32,060
														Subtotal = $320,587

Issue Date FY: 2021 ( Subtotal = $320,762 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	15	2/10/2021	NON-COMPETING CONTINUATION	$32,078
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	15	12/9/2020	NON-COMPETING CONTINUATION	$288,684
														Subtotal = $320,762

Issue Date FY: 2020 ( Subtotal = $320,921 )
2020	2020	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	14	12/25/2019	NON-COMPETING CONTINUATION	$288,827
2020	2020	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	14	2/27/2020	NON-COMPETING CONTINUATION	$32,094
														Subtotal = $320,921

Issue Date FY: 2019 ( Subtotal = $321,067 )
2019	2019	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	13	1/16/2019	COMPETING CONTINUATION	$321,067
2019	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	12	4/24/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $321,067

Issue Date FY: 2017 ( Subtotal = $298,731 )
2017	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	12	11/21/2016	NON-COMPETING CONTINUATION	$268,857
2017	2017	CORNELL UNIVERSITY, INC	373 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	12	8/8/2017	NON-COMPETING CONTINUATION	$29,874
														Subtotal = $298,731

Issue Date FY: 2016 ( Subtotal = $269,213 )
2016	2016	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	11	11/25/2015	NON-COMPETING CONTINUATION	$269,213
														Subtotal = $269,213

Issue Date FY: 2015 ( Subtotal = $299,477 )
2015	2015	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	10	1/27/2015	NON-COMPETING CONTINUATION	$29,948
2015	2015	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	10	11/21/2014	NON-COMPETING CONTINUATION	$269,529
														Subtotal = $299,477

Issue Date FY: 2014 ( Subtotal = $302,357 )
2014	2014	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	9	1/8/2014	COMPETING CONTINUATION	$302,357
2014	2012	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	8	1/3/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $302,357

Issue Date FY: 2012 ( Subtotal = $291,725 )
2012	2012	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	8	8/1/2012	NON-COMPETING CONTINUATION	$291,725
														Subtotal = $291,725

Issue Date FY: 2011 ( Subtotal = $291,495 )
2011	2011	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	7	8/1/2011	NON-COMPETING CONTINUATION	$291,495
														Subtotal = $291,495

Issue Date FY: 2010 ( Subtotal = $294,543 )
2010	2010	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	6	8/16/2010	NON-COMPETING CONTINUATION	$294,543
														Subtotal = $294,543

Issue Date FY: 2009 ( Subtotal = $292,423 )
2009	2009	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	001	5	8/14/2009	COMPETING CONTINUATION	$292,423
2009	2008	CORNELL UNIVERSITY	373 PINE ROAD	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	4	8/14/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $292,423

Issue Date FY: 2008 ( Subtotal = $240,375 )
2008	2008	CORNELL UNIVERSITY, ENDOWED COLLEGES	EAST HILL PLAZA	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	4	9/4/2008	NON-COMPETING CONTINUATION	$240,375
														Subtotal = $240,375

Issue Date FY: 2007 ( Subtotal = $241,413 )
2007	2007	CORNELL UNIVERSITY, ENDOWED COLLEGES	EAST HILL PLAZA	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	3	8/27/2007	NON-COMPETING CONTINUATION	$241,413
														Subtotal = $241,413

Issue Date FY: 2006 ( Subtotal = $250,077 )
2006	2006	CORNELL UNIVERSITY, ENDOWED COLLEGES	EAST HILL PLAZA	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	2	8/24/2006	NON-COMPETING CONTINUATION	$250,077
														Subtotal = $250,077

Issue Date FY: 2005 ( Subtotal = $270,161 )
2005	2005	CORNELL UNIVERSITY, ENDOWED COLLEGES	EAST HILL PLAZA	ITHACA	NY	14850	TOMPKINS	USA	Biomedical Research and Research Training	000	1	8/22/2005	NEW	$270,161
														Subtotal = $270,161

Grand Total All Awards = $4,625,327

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Molecular and Evolutionary Genetics of Meiotic Drive

Award Number: R01GM074737

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/16/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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