A population genomic characterization of copy number variation in the opportunistic fungal pathogen Aspergillus fumigatus.

Aspergillus fumigatus is a potentially deadly opportunistic fungal pathogen. Molecular studies have shaped our understanding of the genes, proteins, and molecules that contribute to A. fumigatus pathogenicity, but few studies have characterized genome-wide patterns of genetic variation at the population level. Of A. fumigatus genomic studies to-date, most focus mainly on single nucleotide polymorphisms and large structural variants, while overlooking the contribution of copy number variation (CNV). CNV is a class of small structural variation defined as loci that vary in their number of copies between individuals due to duplication, gain, or deletion. CNV can influence phenotype, including fungal virulence. In the present study, we characterized the population genomic patterns of CNV in a diverse collection of 71 A. fumigatus isolates using publicly available sequencing data. We used genome-wide single nucleotide polymorphisms to infer the population structure of these isolates and identified three populations consisting of at least 8 isolates. We then computationally predicted genome-wide CNV profiles for each isolate and conducted analyses at the species-, population-, and individual levels. Our results suggest that CNV contributes to genetic variation in A. fumigatus, with ~10% of the genome being CN variable. Our analysis indicates that CNV is non-randomly distributed across the A. fumigatus genome, and is overrepresented in subtelomeric regions. Analysis of gene ontology categories in genes that overlapped CN variants revealed an enrichment of genes related to transposable element and secondary metabolism functions. We further identified 72 loci containing 33 genes that showed divergent copy number profiles between the three A. fumigatus populations. Many of these genes encode proteins that interact with the cell surface or are involved in pathogenicity. Our results suggest that CNV is an important source of genetic variation that could account for some of the phenotypic differences between A. fumigatus populations and isolates.