Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level
2017
Rhodes, Johanna | Desjardins, Christopher | Sykes, Sean | Beale, Mathew | Vanhove, Mathieu | Sakthikumar, Sharadha | Chen, Yuan | Gujja, Sharvari | Saif, Sakina | Chowdhary, Anuradha | Lawson, Daniel John | Ponzio, Vinicius | Colombo, Arnaldo Lopes | Meyer, Wieland | Engelthaler, David | Hagen, Ferry | Illnait-Zaragozi, Maria Teresa | Alanio, Alexandre | Vreulink, Jo-Marie | Heitman, Joseph | Perfect, John | Litvintseva, Anastasia | Bicanic, Tihana | Harrison, Thomas | Fisher, Matthew | Cuomo, Christina | Imperial College London | Broad Institute of MIT and Harvard (BROAD INSTITUTE) ; Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston] | St George's, University of London | The Wellcome Trust Sanger Institute [Cambridge] | Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Duke University Medical Center | University of Bristol [Bristol] | Universidade Federal de São Paulo = Federal University of São Paulo | The University of Sydney | Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ) ; Pasteur Network (Réseau International des Instituts Pasteur) | The Translational Genomics Research Institute (TGen) | Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands] | Pedro Kouri Institute of Tropical Medicine | Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Mycologie moléculaire ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) | Stellenbosch University | This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under grant number U19 AI-110818 and by the National Human Genome Research Institute grant number U54HG003067 to the Broad Institute. Support to J.R.P. came from Public Health Service grants AI73896 and AI93257. J.R. and M.A.B. were supported by a United Kingdom Medical Research Council (MRC) grant awarded to M.C.F., T.B., and T.S.H. (MRC MR/K000373/1). M.V. was supported by a United Kingdom Natural Environment Research Council Ph.D. studentship. J.H. was supported by National Institutes of Health grants AI-39115-19 and AI-50113-13. D.J.L. was funded by Wellcome Trust grant number WT104125MA.
International audience
Показать больше [+] Меньше [-]Английский. 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.
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