RT Journal Article
SR Electronic
T1 Population genomics of <em>Cryptococcus neoformans</em> var. <em>grubii</em> reveals new biogeographic relationships and finely maps hybridization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 132894
DO 10.1101/132894
A1 Johanna Rhodes
A1 Christopher A. Desjardins
A1 Sean M. Sykes
A1 Mathew A. Beale
A1 Mathieu Vanhove
A1 Sharadha Sakthikumar
A1 Yuan Chen
A1 Sharvari Gujja
A1 Sakina Saif
A1 Anuradha Chowdhary
A1 Daniel John Lawson
A1 Vinicius Ponzio
A1 Arnaldo Lopes Colombo
A1 Wieland Meyer
A1 David M. Engelthaler
A1 Ferry Hagen
A1 Maria Teresa Illnait-Zaragozi
A1 Alexandre Alanio
A1 Jo-Marie Vreulink
A1 Joseph Heitman
A1 John R. Perfect
A1 Anastasia Litvintseva
A1 Tihana Bicanic
A1 Thomas S. Harrison
A1 Matthew C. Fisher
A1 Christina A. Cuomo
YR 2017
UL http://biorxiv.org/content/early/2017/05/12/132894.abstract
AB Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically HIV/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 characterized 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 A/A) and of hybrids with C. neoformans var. neoformans (serotype A/D) 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 revealed 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.Author Summary Cryptococcus neoformans var. grubii is a human fungal pathogen of immunocompromised individuals that has global clinical impact, causing half a million deaths per year. Substantial genetic substructure exists for this pathogen, with two lineages found globally (VNI, VNII) whereas a third has appeared confined to sub-Saharan Africa (VNB). Here, we utilized genome sequencing of a large set of global isolates to examine the genetic diversity, hybridization, and biogeography of these lineages. We found that while the three major lineages are well separated, recombination between the lineages has occurred, notably resulting in hybrid isolates with segmented ancestry across the genome. In addition, we showed that isolates from South America are placed within the VNB lineage, formerly thought to be confined to Africa, and that there is phylogenetic separation between these geographies that substantially expands the diversity of these lineages. Our findings provide a new framework for further studies of the dynamics of natural populations of C. neoformans var. grubii.