Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis

Abstract

species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable Human infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of populations during their spread across mammals. Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that may have undergone recent host shifts. The results demonstrate that strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.

Genotyping of Pneumocystis jirovecii by Use of a New Simplified Nomenclature System Based on the Internal Transcribed Spacer Regions and 5.8S rRNA Gene of the rRNA Operon

“…In phylogenetic analysis (see Fig. S1 in the supplemental material), there was no apparent clustering (bootstrap values of Ͻ70% for all main branches), suggesting no correlation with geography, consistent with the results of a recent population genetic analysis (23).…”

Fifty Aureobasidium pullulans genomes reveal a recombining polyextremotolerant generalist

“…Hemileia vastatrix is the cause of coffee leaf rust, and it was initially believed to be a genetically unstructured and cosmopolitan species, but was later revealed to be a complex of cryptic species with marked host tropism (Silva et al ., ). Population structuring (with no significant geographic structure) has been reported for the pathogenic Pneumocystis species (Cissé et al ., ). The same was noted for the yeast Metschnikowia reukaufii , where the lineages detected were reported to be metabolically distinct (Dhami et al ., ).…”

Genotyping Pneumocystis jirovecii: Impacting Our Understanding of Interhuman Transmission

“…Nonetheless, genetic differentiation was limited when considering all three populations. The recent study of Cissé et al using whole genome sequencing found no evidence of population structuring by geography [88].…”

“…Indeed, the lack of culture systems for P. jirovecii in a global approach to sequencing resulted in a huge quantity of undesirable DNA from humans and other microorganisms present in the BAL fluid; a dedicated software was used to eliminate human sequences [86].The first assembly was followed by a second one in 2015, and this allowed genome comparison of two different strains [34]. A recent study by Cissé et al compared the whole genome sequence of 33 P. jirovecii strains to determine genomic variation and population structure [88]. This study found that the natural population maintains a high level of genetic variation despite low levels of recombination.…”