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A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence
The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently diversified, forming a species complex containing members with distinct morphologies, distrib...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302566/ https://www.ncbi.nlm.nih.gov/pubmed/22375073 http://dx.doi.org/10.1128/mBio.00310-11 |
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author | Morrow, Carl A. Lee, I. Russel Chow, Eve W. L. Ormerod, Kate L. Goldinger, Anita Byrnes, Edmond J. Nielsen, Kirsten Heitman, Joseph Schirra, Horst Joachim Fraser, James A. |
author_facet | Morrow, Carl A. Lee, I. Russel Chow, Eve W. L. Ormerod, Kate L. Goldinger, Anita Byrnes, Edmond J. Nielsen, Kirsten Heitman, Joseph Schirra, Horst Joachim Fraser, James A. |
author_sort | Morrow, Carl A. |
collection | PubMed |
description | The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently diversified, forming a species complex containing members with distinct morphologies, distributions, and pathologies of infection. We have investigated structural changes in genomic architecture such as inversions and translocations that distinguish the most pathogenic variety, Cryptococcus neoformans var. grubii, from the less clinically prevalent Cryptococcus neoformans var. neoformans and Cryptococcus gattii. Synteny analysis between the genomes of the three Cryptococcus species/varieties (strains H99, JEC21, and R265) reveals that C. neoformans var. grubii possesses surprisingly few unique genomic rearrangements. All but one are relatively small and are shared by all molecular subtypes of C. neoformans var. grubii. In contrast, the large translocation peculiar to the C. neoformans var. grubii type strain is found in all tested subcultures from multiple laboratories, suggesting that it has possessed this rearrangement since its isolation from a human clinical sample. Furthermore, we find that the translocation directly disrupts two genes. The first of these encodes a novel protein involved in metabolism of glucose at human body temperature and affects intracellular levels of trehalose. The second encodes a homeodomain-containing transcription factor that modulates melanin production. Both mutations would be predicted to increase pathogenicity; however, when recreated in an alternate genetic background, these mutations do not affect virulence in animal models. The type strain of C. neoformans var. grubii in which the majority of molecular studies have been performed is therefore atypical for carbon metabolism and key virulence attributes. |
format | Online Article Text |
id | pubmed-3302566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33025662012-03-15 A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence Morrow, Carl A. Lee, I. Russel Chow, Eve W. L. Ormerod, Kate L. Goldinger, Anita Byrnes, Edmond J. Nielsen, Kirsten Heitman, Joseph Schirra, Horst Joachim Fraser, James A. mBio Research Article The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently diversified, forming a species complex containing members with distinct morphologies, distributions, and pathologies of infection. We have investigated structural changes in genomic architecture such as inversions and translocations that distinguish the most pathogenic variety, Cryptococcus neoformans var. grubii, from the less clinically prevalent Cryptococcus neoformans var. neoformans and Cryptococcus gattii. Synteny analysis between the genomes of the three Cryptococcus species/varieties (strains H99, JEC21, and R265) reveals that C. neoformans var. grubii possesses surprisingly few unique genomic rearrangements. All but one are relatively small and are shared by all molecular subtypes of C. neoformans var. grubii. In contrast, the large translocation peculiar to the C. neoformans var. grubii type strain is found in all tested subcultures from multiple laboratories, suggesting that it has possessed this rearrangement since its isolation from a human clinical sample. Furthermore, we find that the translocation directly disrupts two genes. The first of these encodes a novel protein involved in metabolism of glucose at human body temperature and affects intracellular levels of trehalose. The second encodes a homeodomain-containing transcription factor that modulates melanin production. Both mutations would be predicted to increase pathogenicity; however, when recreated in an alternate genetic background, these mutations do not affect virulence in animal models. The type strain of C. neoformans var. grubii in which the majority of molecular studies have been performed is therefore atypical for carbon metabolism and key virulence attributes. American Society of Microbiology 2012-02-28 /pmc/articles/PMC3302566/ /pubmed/22375073 http://dx.doi.org/10.1128/mBio.00310-11 Text en Copyright © 2012 Morrow et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Morrow, Carl A. Lee, I. Russel Chow, Eve W. L. Ormerod, Kate L. Goldinger, Anita Byrnes, Edmond J. Nielsen, Kirsten Heitman, Joseph Schirra, Horst Joachim Fraser, James A. A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence |
title | A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence |
title_full | A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence |
title_fullStr | A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence |
title_full_unstemmed | A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence |
title_short | A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence |
title_sort | unique chromosomal rearrangement in the cryptococcus neoformans var. grubii type strain enhances key phenotypes associated with virulence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302566/ https://www.ncbi.nlm.nih.gov/pubmed/22375073 http://dx.doi.org/10.1128/mBio.00310-11 |
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