Cell wall protein variation, break-induced replication, and subtelomere dynamics in Candida glabrata

Area of Science:

• Microbiology
• Genomics
• Pathogenesis

Background:

• Candida glabrata is a significant opportunistic human pathogen causing disseminated candidiasis.
• Host cell adherence, vital for C. glabrata infection, is mediated by adhesin-like proteins (ALPs), many located in subtelomeric regions.

Purpose of the Study:

• To perform de novo genome assembly of C. glabrata strains using long reads.
• To analyze genomic variations, chromosome rearrangements, and subtelomeric changes between strains.
• To investigate the impact of these changes on ALP gene complement and structure.

Main Methods:

• De novo genome assembly using long single-molecule real-time (SMRT) reads.
• High-quality telomere-to-telomere chromosome assembly.
• Comparative genomic analysis of C. glabrata strains BG2 and BG3993.
• Characterization of subtelomeric regions and ALP gene variations.

Main Results:

• High single nucleotide variant (SNV) frequencies (~0.5%-1%) were observed across genomes, including subtelomeres.
• Significant length variations in ALP genes due to copy number changes in tandem repeats were documented.
• Chromosome rearrangements in subtelomeric regions predominantly affect terminal ALP genes (14/16 cases).
• Evidence suggests break-induced replication mediates these subtelomeric rearrangements.

Conclusions:

• Subtelomeric regions in C. glabrata exhibit constrained evolutionary changes impacting ALP gene repertoire.
• Genomic plasticity in subtelomeres, particularly affecting ALP genes, is a key feature of C. glabrata.
• Understanding these rearrangements provides insights into the pathogenic mechanisms of C. glabrata.