Cell wall protein variation, break‐induced replication, and subtelomere dynamics in Candida glabrata. Issue 1 (17th March 2021)

• Record Type: Journal Article
• Authors: Xu, Zhuwei; Green, Brian; Benoit, Nicole; Sobel, Jack D.; Schatz, Michael C.; Wheelan, Sarah; Cormack, Brendan P.
• Is Part Of: Molecular microbiology. Volume 116:Issue 1(2021)
• Page Start: 260
• Page End: 276
• Publication Date: 2021-03-17
• Subjects: BIR -- fungal adhesins -- GPI‐CWP; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14707
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: Candida glabrata is an opportunistic pathogen of humans, responsible for up to 30% of disseminated candidiasis. Adherence of C. glabrata to host cells is mediated by adhesin‐like proteins (ALPs), about half of which are encoded in the subtelomeres. We performed a de novo assembly of two C. glabrata strains, BG2 and BG3993, using long single‐molecule real‐time (SMRT) reads, and constructed high‐quality telomere‐to‐telomere assemblies of all 13 chromosomes to assess differences between C. glabrata strains. We documented variation between strains, and in agreement with earlier studies, found high (~0.5%–1%) frequencies of SNVs across the genome, including within subtelomeric regions. We documented changes in ALP gene structure and complement: there are large length differences in ALP genes in different strains, resulting from copy number variation in tandem repeats. We compared strains to characterize chromosome rearrangement events including within the poorly characterized subtelomeric regions. We show that rearrangements within the subtelomere regions all affect ALP‐encoding genes, and 14/16 involve just the most terminal ALP gene. We present evidence that these rearrangements are mediated by break‐induced replication. This study highlights the constrained nature of subtelomeric changes impacting ALP gene complement and subtelomere structure. Abstract : Candida glabrata subtelomeres are enriched for genes encoding adhesins and adhesin‐like proteins; most strain to strain variation in gene complement is due to subtelomeric changes. We have used long read sequencing to assemble the genomes, including subtelomeres, of three strains. We show that variation in subtelomere gene complement is limited, and primarily due to translocation, duplication and deletion of the most telomeric gene for a subset of subtelomeres, likely mediated by break‐induced replication.