# The evolution of copy number variations in the AT-rich Plasmodium genome

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $397,040

## Abstract

PROJECT SUMMARY
Changes in the copy number of large genomic regions, termed copy number variations or CNVs, contribute to
phenotypic diversity and facilitate important processes such as host range and drug resistance. Despite decades
of CNV research, many questions regarding their formation and dynamics remain unanswered. Due to distinctive
genome characteristics, facile in vitro propagation, and the relative simplicity of CNV formation, Plasmodium
falciparum is an exceptional model to study many aspects of CNV-based adaptation. Experimental evolution
demonstrates how this haploid asexual parasite rapidly acquires CNVs in the form of tandem duplications. By
studying the junctions of these CNVs, we have identified the precise genome characteristics that contribute to
their formation in this organism; A/T-rich features of the genome both trigger DNA breakage and facilitate
subsequent error-prone repair. Based on this finding, we hypothesize that the extreme AT content of the P.
falciparum genome (>80%) specifically contributes to its highly adaptive nature. We aim to explore this
hypothesis using different human-infective Plasmodium species, which have genomes exhibiting a range of AT-
content (differing by >20% overall and ~30% in intergenic regions). To do so, we will generate highly accurate
genome assemblies to characterize CNV junctions and the sequences that lead to their formation. We will identify
genome features that contribute to DNA breakage and CNV formation in vivo. We will measure the frequency of
novel CNV generation, under both basal and stressed conditions. These proposed studies will facilitate our
creation of a genomic map of adaptive potential for different malaria species, provide firm evidence for our model
of CNV formation, and define constraints influencing CNV evolution. This knowledge, and the novel methods
developed during this project, will pave the way to developing approaches to limit CNV-based adaptation in
diverse microorganisms, cancers, and other cell types under rapid evolution.

## Key facts

- **NIH application ID:** 10815544
- **Project number:** 5R01AI150856-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jennifer Lynn Guler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $397,040
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10815544

## Citation

> US National Institutes of Health, RePORTER application 10815544, The evolution of copy number variations in the AT-rich Plasmodium genome (5R01AI150856-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10815544. Licensed CC0.

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