Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species
ABSTRACT Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. Histoplasma is endemic in the Ohio and Mississippi River Valleys in the United States and is also distributed worldwide. Previous studies have revealed at...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-02-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02574-21 |
| _version_ | 1818872265153970176 |
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| author | Mark Voorhies Shirli Cohen Terrance P. Shea Semar Petrus José F. Muñoz Shane Poplawski William E. Goldman Todd P. Michael Christina A. Cuomo Anita Sil Sinem Beyhan |
| author_facet | Mark Voorhies Shirli Cohen Terrance P. Shea Semar Petrus José F. Muñoz Shane Poplawski William E. Goldman Todd P. Michael Christina A. Cuomo Anita Sil Sinem Beyhan |
| author_sort | Mark Voorhies |
| collection | DOAJ |
| description | ABSTRACT Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. Histoplasma is endemic in the Ohio and Mississippi River Valleys in the United States and is also distributed worldwide. Previous studies have revealed at least eight clades, each specific to a geographic location: North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B), Eurasian, Netherlands, Australian and African, and an additional distinct lineage (H81) comprised of Panamanian isolates. Previously assembled Histoplasma genomes are highly fragmented, with the highly repetitive G217B (NAm 2) strain, which has been used for most whole-genome-scale transcriptome studies, assembled into over 250 contigs. In this study, we set out to fully assemble the repeat regions and characterize the large-scale genome architecture of Histoplasma species. We resequenced five Histoplasma strains (WU24 [NAm 1], G217B [NAm 2], H88 [African], G186AR [Panama], and G184AR [Panama]) using Oxford Nanopore Technologies long-read sequencing technology. Here, we report chromosomal-level assemblies for all five strains, which exhibit extensive synteny among the geographically distant Histoplasma isolates. The new assemblies revealed that RYP2, a major regulator of morphology and virulence, is duplicated in G186AR. In addition, we mapped previously generated transcriptome data sets onto the newly assembled chromosomes. Our analyses revealed that the expression of transposons and transposon-embedded genes are upregulated in yeast phase compared to mycelial phase in the G217B and H88 strains. This study provides an important resource for fungal researchers and further highlights the importance of chromosomal-level assemblies in analyzing high-throughput data sets. IMPORTANCE Histoplasma species are dimorphic fungi causing significant morbidity and mortality worldwide. These fungi grow as mold in the soil and as budding yeast within the human host. Histoplasma can be isolated from soil in diverse regions, including North America, South America, Africa, and Europe. Phylogenetically distinct species of Histoplasma have been isolated and sequenced. However, for the commonly used strains, genome assemblies have been fragmented, leading to underutilization of genome-scale data. This study provides chromosome-level assemblies of the commonly used Histoplasma strains using long-read sequencing technology. Comparative analysis of these genomes shows largely conserved gene order within the chromosomes. Mapping existing transcriptome data on these new assemblies reveals clustering of transcriptionally coregulated genes. The results of this study highlight the importance of obtaining chromosome-level assemblies in understanding the biology of human fungal pathogens. |
| first_indexed | 2024-12-19T12:36:04Z |
| format | Article |
| id | doaj.art-756b9fc7717b458bb2ddcae21d88b6ae |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T12:36:04Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-756b9fc7717b458bb2ddcae21d88b6ae2022-12-21T20:21:09ZengAmerican Society for MicrobiologymBio2150-75112022-02-0113110.1128/mbio.02574-21Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct SpeciesMark Voorhies0Shirli Cohen1Terrance P. Shea2Semar Petrus3José F. Muñoz4Shane Poplawski5William E. Goldman6Todd P. Michael7Christina A. Cuomo8Anita Sil9Sinem Beyhan10Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USADepartment of Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USABroad Institute of MIT and Harvard, Cambridge, Massachusetts, USADepartment of Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USABroad Institute of MIT and Harvard, Cambridge, Massachusetts, USADepartment of Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USADepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USABroad Institute of MIT and Harvard, Cambridge, Massachusetts, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, USADepartment of Infectious Diseases, J. Craig Venter Institute, La Jolla, California, USAABSTRACT Histoplasma capsulatum, a dimorphic fungal pathogen, is the most common cause of fungal respiratory infections in immunocompetent hosts. Histoplasma is endemic in the Ohio and Mississippi River Valleys in the United States and is also distributed worldwide. Previous studies have revealed at least eight clades, each specific to a geographic location: North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B), Eurasian, Netherlands, Australian and African, and an additional distinct lineage (H81) comprised of Panamanian isolates. Previously assembled Histoplasma genomes are highly fragmented, with the highly repetitive G217B (NAm 2) strain, which has been used for most whole-genome-scale transcriptome studies, assembled into over 250 contigs. In this study, we set out to fully assemble the repeat regions and characterize the large-scale genome architecture of Histoplasma species. We resequenced five Histoplasma strains (WU24 [NAm 1], G217B [NAm 2], H88 [African], G186AR [Panama], and G184AR [Panama]) using Oxford Nanopore Technologies long-read sequencing technology. Here, we report chromosomal-level assemblies for all five strains, which exhibit extensive synteny among the geographically distant Histoplasma isolates. The new assemblies revealed that RYP2, a major regulator of morphology and virulence, is duplicated in G186AR. In addition, we mapped previously generated transcriptome data sets onto the newly assembled chromosomes. Our analyses revealed that the expression of transposons and transposon-embedded genes are upregulated in yeast phase compared to mycelial phase in the G217B and H88 strains. This study provides an important resource for fungal researchers and further highlights the importance of chromosomal-level assemblies in analyzing high-throughput data sets. IMPORTANCE Histoplasma species are dimorphic fungi causing significant morbidity and mortality worldwide. These fungi grow as mold in the soil and as budding yeast within the human host. Histoplasma can be isolated from soil in diverse regions, including North America, South America, Africa, and Europe. Phylogenetically distinct species of Histoplasma have been isolated and sequenced. However, for the commonly used strains, genome assemblies have been fragmented, leading to underutilization of genome-scale data. This study provides chromosome-level assemblies of the commonly used Histoplasma strains using long-read sequencing technology. Comparative analysis of these genomes shows largely conserved gene order within the chromosomes. Mapping existing transcriptome data on these new assemblies reveals clustering of transcriptionally coregulated genes. The results of this study highlight the importance of obtaining chromosome-level assemblies in understanding the biology of human fungal pathogens.https://journals.asm.org/doi/10.1128/mbio.02574-21Histoplasma capsulatumgenome assemblylong-read sequencing |
| spellingShingle | Mark Voorhies Shirli Cohen Terrance P. Shea Semar Petrus José F. Muñoz Shane Poplawski William E. Goldman Todd P. Michael Christina A. Cuomo Anita Sil Sinem Beyhan Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species mBio Histoplasma capsulatum genome assembly long-read sequencing |
| title | Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species |
| title_full | Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species |
| title_fullStr | Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species |
| title_full_unstemmed | Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species |
| title_short | Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species |
| title_sort | chromosome level genome assembly of a human fungal pathogen reveals synteny among geographically distinct species |
| topic | Histoplasma capsulatum genome assembly long-read sequencing |
| url | https://journals.asm.org/doi/10.1128/mbio.02574-21 |
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