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Repetitive DNA as a Driver of Functional and Phenotypic Diversity in Drosophila

Award Number: R01GM166384
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: 09/11/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Repetitive DNA as a Driver of Functional and Phenotypic Diversity in Drosophila - PROJECT SUMMARY Repetitive DNA sequences, including transposable elements (TEs) and copy number variants (CNVs), are a major source of genome structural variants (SVs) that can disrupt genes, alter regulatory elements, and reshape genome architecture, contributing to phenotypic variation, human diseases, and adaptation. However, most SVs involving repetitive sequences in humans and the model organism Drosophila remain undetected by standard short-read sequencing, leaving their functional and evolutionary roles poorly understood. This project will investigate how repetitive DNA shapes gene regulation and phenotypic diversity by comparing two closely related species, D. melanogaster and D. simulans, which share similar evolutionary histories but differ markedly in repeat content. This contrast provides a powerful framework to test whether differences in repeat landscapes lead to differences in functional and phenotypic outcomes. We will generate 25 highly contiguous, centromere-resolved genome assemblies for each species and construct species-specific pangenomes to identify polymorphic TEs and CNVs. Using population genetic models, we will estimate the distribution of fitness effects for different SV classes and compare selective pressures between species. To determine the relative impact of repetitive SVs in two species, we will integrate ATAC-seq, RNA-seq, and Hi-C data from the same strains, mapped to pangenome graphs, to identify regulatory elements created or disrupted by SVs. Functional predictions will be validated using in vivo reporter assays and CRISPR-Cas9 genome editing in both species. Finally, to assess whether phenotypic effects of repeat-associated SVs are conserved across species, we will engineer eight candidate SVs—previously linked to traits such as ethanol tolerance, insecticide resistance, and fecundity—into orthologous loci in D. simulans and measure their phenotypic and fitness effects under relevant selection conditions, comparing outcomes to D. melanogaster. By combining comparative genomics, functional assays, and evolutionary analysis, this research will reveal how differences in repeat content shape genome function and phenotypic diversity. Insights from this work will advance our understanding of genome evolution and inform interpretation of structural variation in natural populations and human disease.


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 = $386,204 )
2026	2026	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	1	9/10/2026	NEW	$386,204
														Subtotal = $386,204

Grand Total All Awards = $386,204

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Repetitive DNA as a Driver of Functional and Phenotypic Diversity in Drosophila

Award Number: R01GM166384

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: 09/11/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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