Genetic Diversity of the Cryptococcus Species Complex Suggests that Cryptococcus gattii Deserves to Have Varieties

Abstract

The Cryptococcus species complex contains two sibling taxa, Cryptococcus neoformans and Cryptococcus gattii. Both species are basidiomycetous yeasts and major pathogens of humans and other mammals. Genotyping methods have identified major haploid molecular types of C. neoformans (VNI, VNII, VNB and VNIV) and of C. gattii (VGI, VGII, VGIII and VGIV). To investigate the phylogenetic relationships among these haploid genotypes, we selected 73 strains from 2000 globally collected isolates investigated in our previous typing studies, representing each of these genotypes and carried out multigene sequence analyses using four genetically unlinked nuclear loci, ACT1, IDE, PLB1 and URA5. The separate or combined sequence analyses of all four loci revealed seven clades with significant support for each molecular type. However, three strains of each species revealed some incongruence between the original molecular type and the sequence-based type obtained here. The topology of the individual gene trees was identical for each clade of C. neoformans but incongruent for the clades of C. gattii indicating recent recombination events within C. gattii. There was strong evidence of recombination in the global VGII population. Both parsimony and likelihood analyses supported three major clades of C. neoformans (VNI/VNB, VNII and VNIV) and four major clades of C. gattii (VGI, VGII, VGIII and VGIV). The sequence variation between VGI, VGIII and VGIV was similar to that between VNI/VNB and VNII. MATa was for the first time identified for VGIV. The VNIV and VGII clades are basal to the C. neoformans or the C. gattii clade, respectively. Divergence times among the seven haploid monophyletic lineages in the Cryptococcus species complex were estimated by applying the hypothesis of the molecular clock. The genetic variation found among all of these haploid monophyletic lineages indicates that they warrant varietal status.

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…Another one has been recorded from 1983 to 2009 in North and South America, in Europe and in Asia (Khayhan et al, 2013). C. gattii and C. neoformans also exhibit very typical near-clades (Tibayrenc and Ayala, 2014b), corroborated by various molecular markers, including AFLP, MLST, PCR fingerprinting, RAPD and RFLP, and strongly linked to serotypes (Bovers et al, 2008;Campbell et al, 2005;Campbell and Carter, 2006;Carriconde et al, 2011;Chaturvedi and Chaturvedi, 2011;Fraser et al, 2005;Khayhan et al, 2013;Lin and Heitman, 2006;Litvintseva and Mitchell, 2012;Ngamskulrungroj et al, 2009;Voelz et al, 2013;Xu, 2006a). In C. gattii, there are 4 'molecular types' (near-clades) I to IV.…”

“…In C. gattii, there are 4 'molecular types' (near-clades) I to IV. In molecular type II, there are three clonal groups a, b and c (RD pattern) (Chaturvedi and Chaturvedi, 2011;Ngamskulrungroj et al, 2009;Voelz et al, 2013). In the cluster (near-clade) VGI of this species, four subdivisions (C1e4) are observed (RD pattern) .…”

“…McManus and Coleman (2014) b Edwards et al (2008) e Feretzaki and Heitman (2013) c Ngamskulrungroj et al (2009) b,e Fargier et al (2011) b,e…”

“…There is strong LD revealed by amplified fragment length polymorphism (AFLP), MLST, PCR fingerprint, RAPD, RFLP and gene sequences in the two sibling species Cryptococcus gattii and C. neoformans (Bovers et al, 2008;Lin and Heitman, 2006;Ngamskulrungroj et al, 2009). In these two species, LD is observed between genetic types and serotypes (Campbell and Carter, 2006).…”

“…The near-clade model therefore gives a convenient and flexible framework for describing new species and subspecies, based on the phylogenetic species concept (Cracraft, 1983). The use of the mixiologic species concept (Mayr, 1940) has been tentatively proposed for some micropathogen species on the basis of occasional genetic exchange (Cacci o and Sprong, 2010;Dykhuizen and Green, 1991;Ngamskulrungroj et al, 2009;Voelz et al, 2013). However, genetic exchange in most micropathogens does not play the same evolutionary role as in metazoa, and cannot be retained as a valid criterion for species definition in their case.…”