Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
AgriMetis, Lutherville, MD, USA.
Mol Microbiol. 2021 Jul;116(1):260-276. doi: 10.1111/mmi.14707. Epub 2021 Mar 17.
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.
光滑假丝酵母是一种人类机会致病菌，可导致多达 30%的播散性念珠菌病。光滑假丝酵母对宿主细胞的黏附是由黏附素样蛋白（ALPs）介导的，其中约一半是由端粒附近编码的。我们使用长单分子实时（SMRT）读取对两种光滑假丝酵母菌株 BG2 和 BG3993 进行从头组装，并构建了所有 13 条染色体的高质量端粒到端粒组装，以评估菌株之间的差异。我们记录了菌株之间的差异，并且与早期研究一致，发现基因组中存在高频率（约 0.5%-1%）的 SNV，包括端粒区域内。我们记录了 ALP 基因结构和补体的变化：不同菌株中 ALP 基因的长度存在很大差异，这是由于串联重复的拷贝数变异所致。我们比较了菌株以表征染色体重排事件，包括在研究较少的端粒区域内。我们表明，端粒区域内的重排都影响了编码 ALP 的基因，其中 14/16 个涉及的只是最末端的 ALP 基因。我们提供的证据表明，这些重排是由断裂诱导复制介导的。本研究强调了影响 ALP 基因补体和端粒结构的端粒变化的约束性质。
