The primary goal for this proposal is to determine how mutations that change genome structure (e.g. duplications or deletions of sections of chromosomes) are acquired and preserved. To accomplish this, the evolutionary forces that govern the fate of such mutations will be inferred by sequencing populations within several species groups of Drosophila. Structural variation is an important source of genetic novelty and is thought to play an important role in the origin of genetic complexity. A general understanding of structural variation is important because it plays major roles in the etiology of cancer, the emergence of pathogen resistance, and the origin of pesticide resistance for plant and animal crop pests, among many other topics of relevance to human health and well-being. The project will be executed by studying genomic variation in pairs of closely related Drosophila species. In order to disentangle the influence of genetic drift and natural selection, genome-wide sequencing data for species pairs that exhibit large differences in their population sizes will be collected. This approach works because, as populations become smaller, genetic drift dominates genetic variation more and more. Conversely, as populations become larger, genetic drift's influence on genetic variation becomes weaker and weaker. Thus, it is predicted that, when natural selection drives the acquisition and maintenance of structural mutations, larger populations will acquire and maintain more variants than smaller ones. However, if genetic drift is the major factor, then smaller populations acquire and maintain more variants than larger ones. The project is split into three major phases. The first is collection of and assembly of reference genome data for each species, which will be done using long molecule sequencing strategies. The second is collection of population sequencing data for use in genotyping structural variants. The final phase is to combine genotype and gene annotations and subject them to evolutionary analysis to address the questions proposed above.

Public Health Relevance

This project aims to increase understanding of the consequences of copying or removing segments of DNA in organisms. Such changes in an organism's DNA can lead to serious consequences for how the organism works, especially when those segments contain genes. In particular, such changes are often associated with cancer and other diseases with a genetic basis, the emergence of pathogen resistance, and the origin of pesticide resistance for plant and animal crop pests, among many other topics of relevance to human health and well-being.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
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Janes, Daniel E
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University of California Irvine
Schools of Arts and Sciences
United States
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Chakraborty, Mahul; VanKuren, Nicholas W; Zhao, Roy et al. (2018) Hidden genetic variation shapes the structure of functional elements in Drosophila. Nat Genet 50:20-25
Solares, Edwin A; Chakraborty, Mahul; Miller, Danny E et al. (2018) Rapid Low-Cost Assembly of the Drosophila melanogaster Reference Genome Using Low-Coverage, Long-Read Sequencing. G3 (Bethesda) 8:3143-3154