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 (65–6499 bp) 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 ~1.6 Mb, 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 represent previously uncharacterized variation in the reference genome.
Bibliographical noteFunding Information:
We thank all members of the Selmecki laboratory, especially Curtis Focht, Alison Guyer, Robert Thomas, and Annette Beach for technical assistance. We thank Dr. Robin Dowell, Dr. Mary Ann Allen, and Dr. Hung-Ji Tsai for feedback on the manuscript and helpful discussions. Support for this research was provided by LB692 NE Tobacco Settlement Biomedical Research Development New Initiative Grant (to AS), NE Established Program to Stimulate Competitive Research (EPSCoR) First Award (to AS), NE Department of Health and Human Services (LB506-2017-55) award (to AS), CURAS Faculty Research Fund Award (to AS), and NIH-NCRR COBRE grant P20RR018788 sub-award (to AS). AF was supported by NIH grant R15 AI090633. The sequencing datasets generated during this study are available in the Sequence Read Archive repository under project PRJNA510147.
© Todd et al.