Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>

ABSTRACT Cryptococcus gattii is a fungal pathogen of humans, causing pulmonary infections in otherwise healthy hosts. To characterize genomic variation among the four major lineages of C. gattii (VGI, -II, -III, and -IV), we generated, annotated, and compared 16 de novo genome assemblies, including...

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Autores principales:	Rhys A. Farrer, Christopher A. Desjardins, Sharadha Sakthikumar, Sharvari Gujja, Sakina Saif, Qiandong Zeng, Yuan Chen, Kerstin Voelz, Joseph Heitman, Robin C. May, Matthew C. Fisher, Christina A. Cuomo
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Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
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spelling	oai:doaj.org-article:5945781eb1b54132a487c9cf353683392021-11-15T15:41:30ZGenome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>10.1128/mBio.00868-152150-7511https://doaj.org/article/5945781eb1b54132a487c9cf353683392015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00868-15https://doaj.org/toc/2150-7511ABSTRACT Cryptococcus gattii is a fungal pathogen of humans, causing pulmonary infections in otherwise healthy hosts. To characterize genomic variation among the four major lineages of C. gattii (VGI, -II, -III, and -IV), we generated, annotated, and compared 16 de novo genome assemblies, including the first for the rarely isolated lineages VGIII and VGIV. By identifying syntenic regions across assemblies, we found 15 structural rearrangements, which were almost exclusive to the VGI-III-IV lineages. Using synteny to inform orthology prediction, we identified a core set of 87% of C. gattii genes present as single copies in all four lineages. Remarkably, 737 genes are variably inherited across lineages and are overrepresented for response to oxidative stress, mitochondrial import, and metal binding and transport. Specifically, VGI has an expanded set of iron-binding genes thought to be important to the virulence of Cryptococcus, while VGII has expansions in the stress-related heat shock proteins relative to the other lineages. We also characterized genes uniquely absent in each lineage, including a copper transporter absent from VGIV, which influences Cryptococcus survival during pulmonary infection and the onset of meningoencephalitis. Through inclusion of population-level data for an additional 37 isolates, we identified a new transcontinental clonal group that we name VGIIx, mitochondrial recombination between VGII and VGIII, and positive selection of multidrug transporters and the iron-sulfur protein aconitase along multiple branches of the phylogenetic tree. Our results suggest that gene expansion or contraction and positive selection have introduced substantial variation with links to mechanisms of pathogenicity across this species complex. IMPORTANCE The genetic differences between phenotypically different pathogens provide clues to the underlying mechanisms of those traits and can lead to new drug targets and improved treatments for those diseases. In this paper, we compare 16 genomes belonging to four highly differentiated lineages of Cryptococcus gattii, which cause pulmonary infections in otherwise healthy humans and other animals. Half of these lineages have not had their genomes previously assembled and annotated. We identified 15 ancestral rearrangements in the genome and over 700 genes that are unique to one or more lineages, many of which are associated with virulence. In addition, we found evidence for recent transcontinental spread, mitochondrial genetic exchange, and positive selection in multidrug transporters. Our results suggest that gene expansion/contraction and positive selection are diversifying the mechanisms of pathogenicity across this species complex.Rhys A. FarrerChristopher A. DesjardinsSharadha SakthikumarSharvari GujjaSakina SaifQiandong ZengYuan ChenKerstin VoelzJoseph HeitmanRobin C. MayMatthew C. FisherChristina A. CuomoAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Rhys A. Farrer Christopher A. Desjardins Sharadha Sakthikumar Sharvari Gujja Sakina Saif Qiandong Zeng Yuan Chen Kerstin Voelz Joseph Heitman Robin C. May Matthew C. Fisher Christina A. Cuomo Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>
description	ABSTRACT Cryptococcus gattii is a fungal pathogen of humans, causing pulmonary infections in otherwise healthy hosts. To characterize genomic variation among the four major lineages of C. gattii (VGI, -II, -III, and -IV), we generated, annotated, and compared 16 de novo genome assemblies, including the first for the rarely isolated lineages VGIII and VGIV. By identifying syntenic regions across assemblies, we found 15 structural rearrangements, which were almost exclusive to the VGI-III-IV lineages. Using synteny to inform orthology prediction, we identified a core set of 87% of C. gattii genes present as single copies in all four lineages. Remarkably, 737 genes are variably inherited across lineages and are overrepresented for response to oxidative stress, mitochondrial import, and metal binding and transport. Specifically, VGI has an expanded set of iron-binding genes thought to be important to the virulence of Cryptococcus, while VGII has expansions in the stress-related heat shock proteins relative to the other lineages. We also characterized genes uniquely absent in each lineage, including a copper transporter absent from VGIV, which influences Cryptococcus survival during pulmonary infection and the onset of meningoencephalitis. Through inclusion of population-level data for an additional 37 isolates, we identified a new transcontinental clonal group that we name VGIIx, mitochondrial recombination between VGII and VGIII, and positive selection of multidrug transporters and the iron-sulfur protein aconitase along multiple branches of the phylogenetic tree. Our results suggest that gene expansion or contraction and positive selection have introduced substantial variation with links to mechanisms of pathogenicity across this species complex. IMPORTANCE The genetic differences between phenotypically different pathogens provide clues to the underlying mechanisms of those traits and can lead to new drug targets and improved treatments for those diseases. In this paper, we compare 16 genomes belonging to four highly differentiated lineages of Cryptococcus gattii, which cause pulmonary infections in otherwise healthy humans and other animals. Half of these lineages have not had their genomes previously assembled and annotated. We identified 15 ancestral rearrangements in the genome and over 700 genes that are unique to one or more lineages, many of which are associated with virulence. In addition, we found evidence for recent transcontinental spread, mitochondrial genetic exchange, and positive selection in multidrug transporters. Our results suggest that gene expansion/contraction and positive selection are diversifying the mechanisms of pathogenicity across this species complex.
format	article
author	Rhys A. Farrer Christopher A. Desjardins Sharadha Sakthikumar Sharvari Gujja Sakina Saif Qiandong Zeng Yuan Chen Kerstin Voelz Joseph Heitman Robin C. May Matthew C. Fisher Christina A. Cuomo
author_facet	Rhys A. Farrer Christopher A. Desjardins Sharadha Sakthikumar Sharvari Gujja Sakina Saif Qiandong Zeng Yuan Chen Kerstin Voelz Joseph Heitman Robin C. May Matthew C. Fisher Christina A. Cuomo
author_sort	Rhys A. Farrer
title	Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>
title_short	Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>
title_full	Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>
title_fullStr	Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>
title_full_unstemmed	Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>
title_sort	genome evolution and innovation across the four major lineages of <named-content content-type="genus-species">cryptococcus gattii</named-content>
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/5945781eb1b54132a487c9cf35368339
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Genome Evolution and Innovation across the Four Major Lineages of <named-content content-type="genus-species">Cryptococcus gattii</named-content>

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