Genome plasticity in Candida albicans is driven by long repeat sequences

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Abstract

Genome rearrangements resulting in copy number variation (CNV) and loss of heterozygosity (LOH) are frequently observed during the somatic evolution of cancer and promote rapid adaptation of fungi to novel environments. In the human fungal pathogen Candida albicans, CNV and LOH confer increased virulence and antifungal drug resistance, yet the mechanisms driving these rearrangements are not completely understood. Here, we unveil an extensive array of long repeat sequences (65-6499bp) that are associated with CNV, LOH, and chromosomal inversions. Many of these long repeat sequences are uncharacterized and encompass one or more coding sequences that are actively transcribed. Repeats associated with genome rearrangements are predominantly inverted and separated by up to ~1.6Mb, an extraordinary distance for homology-based DNA repair/recombination in yeast. These repeat sequences are a significant source of genome plasticity across diverse strain backgrounds including clinical, environmental, and experimentally evolved isolates, and previously uncharacterized variation in the reference genome.

Data availability

All data generated and analyzed during this study are included in the manuscript and supporting files. Source data files have a been provided for Figure 1, Figure 1-figure supplement 1, Figure 2, Figure 2-figure supplement 2, Figure 2-figure supplement 3, Figure 6, and Figure 6-figure supplement 1.All genomic data are deposited in SRA under accession PRJNA510147.

The following data sets were generated

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Article and author information

Author details

Robert T Todd

Department of Medical Microbiology and Immunology, Creighton University Medical School, Omaha, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4522-7124
Tyler D Wikoff

Department of Medical Microbiology and Immunology, Creighton University Medical School, Omaha, United States

Competing interests
The authors declare that no competing interests exist.
Anja Forche

Department of Biology, Bowdoin College, Brunswick, United States

Competing interests
The authors declare that no competing interests exist.
Anna Selmecki

Department of Medical Microbiology and Immunology, Creighton University Medical School, Omaha, United States

For correspondence
annaselmecki@creighton.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3298-2400

Funding

Nebraska LB692 New Initiatives Grants (LB692 NE Tobacco Settlement Biomedical Research Development New Initiative Grant)

Anna Selmecki

Nebraska Established Program to Stimulate Competitive Research (EPSCoR First Award)

Anna Selmecki

Nebraska Department of Health and Human Services (LB506-2017-55)

Anna Selmecki

Creighton University (CURAS Faculty Faculty Research Fund)

Anna Selmecki

National Center for Research Resources (P20RR018788 sub award)

Anna Selmecki

National Institutes of Health (R15 AI090633)

Anja Forche

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.