Genome dynamics and chromosome structural variations in Histoplasma ohiense, a fungal pathogen of humans

Area of Science:

• Medical Mycology
• Genomics
• Fungal Pathogenesis

Background:

• Histoplasma is a genus of thermally dimorphic fungal pathogens causing significant human disease.
• Understanding Histoplasma genome plasticity is crucial for elucidating its pathogenicity.
• Limited genomic data exists for Histoplasma, hindering comprehensive pathogenicity studies.

Purpose of the Study:

• To generate the first telomere-to-telomere genome assemblies for Histoplasma ohiense.
• To investigate genome plasticity and chromosomal structure in H. ohiense.
• To establish a representative genome assembly for H. ohiense.

Main Methods:

• Whole-genome sequencing and assembly of Histoplasma ohiense strains UCSF2 and UCSF3.
• Comparative genomic analysis with the existing G217B reference genome.
• Short-read sequencing of natural H. ohiense isolates to assess chromosomal structure prevalence.
• Mutation rate calculation using passaged H. ohiense isolates.

Main Results:

• Two novel, highly contiguous telomere-to-telomere genome assemblies for H. ohiense strains UCSF2 and UCSF3 were generated.
• These assemblies revealed two reciprocal chromosome translocations differentiating them from each other and the previous reference genome.
• The UCSF3 assembly's chromosome structure was found in the majority (91/94) of natural H. ohiense isolates, indicating it is most representative.
• The mutation rate for H. ohiense was determined to be 2.6 x 10^-10 SNP/base/doubling, the first measurement for the order Onygenales.

Conclusions:

• The Histoplasma genome exhibits significant plasticity, including chromosome translocations.
• A new, representative genome assembly for Histoplasma ohiense has been established.
• This work provides a foundation for future studies on Histoplasma pathogenicity and evolution.