# Genetic variation, admixture and genome structure evolution through the lense of Drosophila genomics

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $376,581

## Abstract

Studies in genetic model organisms are an indispensible mechanism for characterizing the mutational and
selective processes that generate genetic and phenotypic diversity. In particular, Drosophila combines the
advantages of efficient population sampling, well developed experimental techniques, with powerful genome
engineering approaches and is therefore a uniquely valuable system for characterizing the contributions of
genetic variation to phenotypic and fitness variation in natural populations. Towards this broad goal, this
research program will leverage the D. melanogaster system to:
(1) Enhance the Drosophila Genome Nexus (DGN), a widely used database that distributes a uniformly
curated and high quality Drosophila population genomic variation dataset. Specifically, by developing
methods that include known genetic variation rather than mapping to a single haploid reference genome, this
research program will enhance both variation calls at single nucleotide polymorphisms as well as expand our
ability to detect and accurately characterize structural variation. Similarly, research will develop and apply
approaches for accurately delineating heterozygous regions in the genomes of inbred lines. By vastly
improving the database, this reseach will enable a new wave of in-depth analyses of the widely-used DGN.
(2) Reveal the fitness and gene expression consequences of the structural and linked allelic variation
associated with natural chromosomal inversions. Genome engineering techniques enable the construction
of inversions with controlled breakpoints on a genetically homogenous background. Through contrasts with
naturally occurring chromosomal inversions, research will distinguish the impacts of structural and linked allelic
variation on gene expression patterns. In addition, research will investigate the fitness consequences of fine-
scale variation in breakpoint location. Chromatin conformation capture sequencing, Hi-C, will enable the
production of sequencing libraries whose large insert sizes enable inversion breakpoint mapping. Research will
apply this approach to map breakpoints of rare inversions. By comparing breakpoint structures with those of
common inversions, these data will enable direct insights into the mutational forces that generate inversions as
well as how these factors influence natural selection on new chromosomal arrangements.
(3) Investigate the genomic and phenotypic consequences of admixture between genetically divergent
subpopulations. By sequencing several admixed populations of D. melanogaster, research will determine the
relative importance of gene-gene interactions in driving natural selection across diverse admixed populations.
Furthermore, by leverage phenotypic data from one admixed population that has been used for a number of
association studies, research will evaluate the importance of admixture in shaping complex phenotypes long
after the initial gene flow event and develop local ancestry aware approaches for ma...

## Key facts

- **NIH application ID:** 10220995
- **Project number:** 5R35GM128932-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Russell Corbett-Detig
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,581
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220995

## Citation

> US National Institutes of Health, RePORTER application 10220995, Genetic variation, admixture and genome structure evolution through the lense of Drosophila genomics (5R35GM128932-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220995. Licensed CC0.

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