Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level

Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level

Author Rhodes, Johanna Google Scholar
Desjardins, Christopher A. Google Scholar
Sykes, Sean M. Google Scholar
Beale, Mathew A. Google Scholar
Vanhove, Mathieu Google Scholar
Sakthikumar, Sharadha Google Scholar
Chen, Yuan Google Scholar
Gujja, Sharvari Google Scholar
Saif, Sakina Google Scholar
Chowdhary, Anuradha Google Scholar
Lawson, Daniel John Google Scholar
Ponzio, Vinicius Autor UNIFESP Google Scholar
Colombo, Arnaldo Lopes Autor UNIFESP Google Scholar
Meyer, Wieland Google Scholar
Engelthaler, David M. Google Scholar
Hagen, Ferry Google Scholar
Teresa Illnait-Zaragozi, Maria Google Scholar
Alanio, Alexandre Google Scholar
Vreulink, Jo-Marie Google Scholar
Heitman, Joseph Google Scholar
Perfect, John R. Google Scholar
Litvintseva, Anastasia P. Google Scholar
Bicanic, Tihana Google Scholar
Harrison, Thomas S. Google Scholar
Fisher, Matthew C. Google Scholar
Cuomo, Christina A. Google Scholar
Abstract Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterize the major subdivisions, their relative diversity, and the level of genetic exchange between them. While most isolates of C. neoformans var. grubii belong to one of three major lineages (VNI, VNII, and VNB), some haploid isolates show hybrid ancestry including some that appear to have recently interbred, based on the detection of large blocks of each ancestry across each chromosome. Many isolates display evidence of aneuploidy, which was detected for all chromosomes. In diploid isolates of C. neoformans var. grubii (serotype AA) and of hybrids with C. neoformans var. neoformans (serotype AD) such aneuploidies have resulted in loss of heterozygosity, where a chromosomal region is represented by the genotype of only one parental isolate. Phylogenetic and population genomic analyses of isolates from Brazil reveal that the previously "African" VNB lineage occurs naturally in the South American environment. This suggests migration of the VNB lineage between Africa and South America prior to its diversification, supported by finding ancestral recombination events between isolates from different lineages and regions. The results provide evidence of substantial population structure, with all lineages showing multi-continental distributions

demonstrating the highly dispersive nature of this pathogen.
Keywords Cryptococcus
genome sequence
Language English
Sponsor National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services
National Human Genome Research Institute (NHGRI)
U.S. Public Health Service (USPHS)
United Kingdom Medical Research Council (MRC)
United Kingdom Natural Environment Research Council
National Institutes of Health (NIH)
Wellcome Trust (WT)
Grant number NIAID: U19 AI-110818
NHGRI: U54HG003067
USPHS: AI73896
USPHS: AI93257
MRC: MR/K000373/1
NIH: AI-39115-19
NIH: AI-50113-13
WT: 104125MA
Date 2017
Published in Genetics. Bethesda, v. 207, n. 1, p. 327-346, 2017.
ISSN 0016-6731 (Sherpa/Romeo, impact factor)
Publisher Genetics Society America
Extent 327-346
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000409179800025

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