Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak

‘Same-sex’ mating game A virulent strain of the fungus Cryptococcus gattii emerged on Vancouver Island, Canada in 1999, causing an outbreak of meningoencephalitis, and it is still infecting humans and animals in the region. This was a surprise: C. gattii is normally restricted to the tropics where it grows on eucalyptus trees and only occasionally infects animals and humans. Geneticists now report that the outbreak was caused by genetic combination of the mildly pathogenic Australian incomer with another isolate of an unknown origin. Remarkably, these fungi combined via sexual reproduction to produce a hypervirulent strain, despite the fact that both were of the same ‘sex’. Both are classified ‘α’ rather than ‘a’ strains. It remains to be seen if such mating is common in the wild, and if it occurs in other parasites, such as Trypanosoma , Leishmania and Plasmodium falciparum , where similar α/a mating types are found. Genealogy can illuminate the evolutionary path of important human pathogens. In some microbes, strict clonal reproduction predominates, as with the worldwide dissemination of Mycobacterium leprae , the cause of leprosy 1 . In other pathogens, sexual reproduction yields clones with novel attributes, for example, enabling the efficient, oral transmission of the parasite Toxoplasma gondii 2 . However, the roles of clonal or sexual propagation in the origins of many other microbial pathogen outbreaks remain unknown, like the recent fungal meningoencephalitis outbreak on Vancouver Island, Canada, caused by Cryptococcus gattii 3 . Here we show that the C. gattii outbreak isolates comprise two distinct genotypes. The majority of isolates are hypervirulent and have an identical genotype that is unique to the Pacific Northwest. A minority of the isolates are significantly less virulent and share an identical genotype with fertile isolates from an Australian recombining population. Genotypic analysis reveals evidence of sexual reproduction, in which the majority genotype is the predicted offspring. However, instead of the classic a–α sexual cycle, the majority outbreak clone appears to have descended from two α mating-type parents. Analysis of nuclear content revealed a diploid environmental isolate homozygous for the major genotype, an intermediate produced during same-sex mating. These studies demonstrate how cryptic same-sex reproduction can enable expansion of a human pathogen to a new geographical niche and contribute to the ongoing production of