Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis

mBio

Lisa Bishop¹  Geetha Kutty¹  Ousmane H. Cissé¹  Yueqin Liu¹  Joseph A. Kovacs¹  Liang Ma¹  Xilong Deng¹  Pavel P. Khil²  John P. Dekker²  Jason E. Stajich³  Christina A. Cuomo⁴  Philippe M. Hauser⁵  Vanessa Hirsch⁶  Richard A. Lempicki⁷  Da Wei Huang⁸  Marco Pagni⁹ 

[1] Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA;Department of Laboratory Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA;Department of Plant Pathology and Microbiology and Institute for Integrative Genome Biology, University of California, Riverside, Riverside, California, USA;Infectious Disease and Microbiome Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland;Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA;Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA;Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA;Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland;

关键词: evolutionary biology;    genetic diversity;    genetic recombination;    pneumonia;    population structure;   

DOI  :  10.1128/mBio.00381-18

来源: DOAJ

【 摘 要 】

ABSTRACT Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro. Human Pneumocystis 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 Pneumocystis 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 Pneumocystis 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 Pneumocystis populations during their spread across mammals. IMPORTANCE Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. Pneumocystis, a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, Pneumocystis can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different Pneumocystis 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 Pneumocystis may have undergone recent host shifts. The results demonstrate that Pneumocystis strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.

【 授权许可】

Unknown