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The evolution and diversity of mutation, molecular fidelity, and genome structure

Award Number: R35GM142916
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: 08/06/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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The evolution and diversity of mutation, molecular fidelity, and genome structure - Project Summary Abstract The structure and sequence of genomes is shaped by the forces of mutation, selection, and drift acting in the context of different life histories and environments. Over evolutionary timescales, changes to genome structure and content are associated with vast phenotypic changes between and within species, while throughout the lifetime of an organism individual cells accumulate somatic mutations and germ cells accumulate damage and lesions that are passed down to progeny. We seek to understand the processes that guide these changes to genomes across different timescales through several distinct but interrelated questions. What are the genetic causes and genetic consequences of extreme variation in life history traits across vertebrates? How does genetics and variation in life history traits impact the Aidelity of molecular processes across taxa? How do processes of mutation and selection impact genome structural diversity across population, species, and cellular scales? Our research to date has uncovered novel structural and single nucleotide variants that contribute to life histories, as well as the ways in which patterns of genetic diversity are shaped by these life history shifts. Our future work will build upon our research in non-model organisms such as bats and rockAish to understand the genetic innovations that underlie life history trait adaptations and, in turn, how such life history changes can shape genomic diversity. We have also identiAied patterns of age-associated somatic evolution in mitochondrial genomes and have developed novel statistical approaches to quantify the distinct roles of genetics and aging on gene expression patterns in aging tissues. Our future work will focus on understanding the mutational processes underlying germline de-novo structural mutation in vertebrates as well as how the diversity of mutational spectra has evolved across vertebrates. We have resolved the structural diversity, evolutionary history, and adaptive and medical relevance of complex loci in the human genome and the genomes of other diverse vertebrates. Our future research will focus on further dissecting complex structurally variable loci in humans and other species as well as characterizing the diversity and distribution of structural variation across the vertebrate tree of life. Together, our work seeks to understand the fundamental evolutionary processes that have shaped genomic architectures, mutational phenotypes, and life histories across organismal, population, and cellular scales.


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: 2026 ( Subtotal = $423,236 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Biomedical Research and Research Training	000	6	5/8/2026	COMPETING CONTINUATION	$423,236
														Subtotal = $423,236

Issue Date FY: 2025 ( Subtotal = $401,250 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	5	6/25/2025	NON-COMPETING CONTINUATION	$401,250
														Subtotal = $401,250

Issue Date FY: 2024 ( Subtotal = $514,831 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	001	4	6/21/2024	SUPPLEMENT FOR EXPANSION	$113,581
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	4	6/19/2024	NON-COMPETING CONTINUATION	$401,250
														Subtotal = $514,831

Issue Date FY: 2023 ( Subtotal = $401,250 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	3	6/13/2023	NON-COMPETING CONTINUATION	$401,250
														Subtotal = $401,250

Issue Date FY: 2022 ( Subtotal = $401,250 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	2	6/21/2022	NON-COMPETING CONTINUATION	$401,250
														Subtotal = $401,250

Issue Date FY: 2021 ( Subtotal = $401,250 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Biomedical Research and Research Training	000	1	8/6/2021	NEW	$401,250
														Subtotal = $401,250

Grand Total All Awards = $2,543,067

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The evolution and diversity of mutation, molecular fidelity, and genome structure

Award Number: R35GM142916

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: 08/06/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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