Replication stress increases de novo CNVs across the malaria parasite genome

dc.contributor.authorBrown, Noah
dc.contributor.authorLuniewski, Aleksander
dc.contributor.authorYu, Xuanxuan
dc.contributor.authorWarthan, Michelle
dc.contributor.authorLiu, Shiwei
dc.contributor.authorZulawinska, Julia
dc.contributor.authorAhmad, Syed
dc.contributor.authorCongdon, Molly
dc.contributor.authorSantos, Webster
dc.contributor.authorXiao, Feifei
dc.contributor.authorGuler, Jennifer L.
dc.contributor.departmentRadiology and Imaging Sciences, School of Medicine
dc.date.accessioned2025-02-20T16:43:41Z
dc.date.available2025-02-20T16:43:41Z
dc.date.issued2024-12-31
dc.description.abstractChanges in the copy number of large genomic regions, termed copy number variations (CNVs), contribute to important phenotypes in many organisms. CNVs are readily identified using conventional approaches when present in a large fraction of the cell population. However, CNVs that are present in only a few genomes across a population are often overlooked but important; if beneficial under specific conditions, a de novo CNV that arises in a single genome can expand during selection to create a larger population of cells with novel characteristics. While the reach of single cell methods to study de novo CNVs is increasing, we continue to lack information about CNV dynamics in rapidly evolving microbial populations. Here, we investigated de novo CNVs in the genome of the Plasmodium parasite that causes human malaria. The highly AT-rich P. falciparum genome readily accumulates CNVs that facilitate rapid adaptation to new drugs and host environments. We employed a low-input genomics approach optimized for this unique genome as well as specialized computational tools to evaluate the de novo CNV rate both before and after the application of stress. We observed a significant increase in genomewide de novo CNVs following treatment with a replication inhibitor. These stress-induced de novo CNVs encompassed genes that contribute to various cellular pathways and tended to be altered in clinical parasite genomes. This snapshot of CNV dynamics emphasizes the connection between replication stress, DNA repair, and CNV generation in this important microbial pathogen.
dc.eprint.versionPreprint
dc.identifier.citationBrown N, Luniewski A, Yu X, et al. Replication stress increases de novo CNVs across the malaria parasite genome. Preprint. bioRxiv. 2024;2024.12.19.629492. Published 2024 Dec 31. doi:10.1101/2024.12.19.629492
dc.identifier.urihttps://hdl.handle.net/1805/45895
dc.language.isoen_US
dc.publisherbioRxiv
dc.relation.isversionof10.1101/2024.12.19.629492
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.sourcePMC
dc.subjectCopy number variations (CNVs)
dc.subjectPhenotypes
dc.subjectMicrobial populations
dc.titleReplication stress increases de novo CNVs across the malaria parasite genome
dc.typeArticle
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