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Published on: May 27, 2022
Using aCGH to study intraspecific genetic variability in two pathogenic molds, Aspergillus fumigatus and Aspergillus
Natalie D Fedorova1, Stephanie Harris, Dan Chen
1The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA. natalief@jcvi.org
Abstract:
We have examined the feasibility of using array comparative genomic hybridization (aCGH) to explore intraspecific genetic variability at the genomic level in two pathogenic molds, Aspergillus fumigatus and Aspergillus flavus. Our analysis showed that strain-specific genes may comprise up to 2% of their genomes in comparison to isolates from different vegetative (heterokaryon) compatibility groups (VCGs). In contrast, isolates with the same VCG affiliations have almost identical gene content. Most isolate-specific genes are annotated as 'hypothetical' and located in a few large subtelomeric indels. The list includes highly polymorphic loci that contain putative het (heterokaryon compatibility) loci, which determine the individual's VCG during parasexual crossing. Incidentally, VCGs in both species seem to be significantly associated with either alpha or HMG mating type (Chi-square test, P=0.05). In conclusion CGH can be used to effectively to identify isolate-specific genes in Aspergillus species. Preliminary evidence suggests that gene flow in both species is largely constrained by VCG boundaries, although further VCG sampling is required to confirm this observation.
Insights
Array comparative genomic hybridization (aCGH) reveals genetic differences in pathogenic molds like Aspergillus. Strain-specific genes, often hypothetical, are linked to vegetative compatibility groups (VCGs), suggesting VCGs limit gene flow.
Area of Science:
- Genomics
- Mycology
- Molecular Biology
Background:
- Intraspecific genetic variability is crucial for understanding pathogen evolution and adaptation.
- Pathogenic molds such as Aspergillus fumigatus and Aspergillus flavus pose significant threats to human and animal health.
- Previous studies have highlighted genetic diversity within Aspergillus species, but genomic-level exploration of intraspecific variation has been limited.
Purpose of the Study:
- To assess the feasibility of array comparative genomic hybridization (aCGH) for investigating genomic-level genetic variability within Aspergillus species.
- To identify and characterize strain-specific genes in Aspergillus fumigatus and Aspergillus flavus.
- To explore the relationship between genetic variability, vegetative (heterokaryon) compatibility groups (VCGs), and mating types in these molds.
Main Methods:
- Array comparative genomic hybridization (aCGH) was employed to compare the genomes of different isolates of Aspergillus fumigatus and Aspergillus flavus.
- Isolates were categorized based on their vegetative (heterokaryon) compatibility groups (VCGs).
- Statistical analyses, including Chi-square tests, were used to associate genetic data with VCGs and mating types.
Main Results:
- Strain-specific genes were found to constitute up to 2% of the genomes when comparing isolates from different VCGs.
- Isolates within the same VCG exhibited nearly identical gene content.
- Most isolate-specific genes were annotated as 'hypothetical' and located in subtelomeric regions, including polymorphic loci associated with heterokaryon compatibility (het) loci.
- VCGs in both species showed a significant association with alpha or HMG mating types (P=0.05).
Conclusions:
- aCGH is an effective method for identifying isolate-specific genes in Aspergillus species.
- Preliminary findings suggest that gene flow in Aspergillus fumigatus and Aspergillus flavus is largely restricted by VCG boundaries.
- Further sampling across a wider range of VCGs is necessary to definitively confirm the role of VCGs in constraining gene flow.

