Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>

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 ri...

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Autores principales:	Ousmane H. Cissé, Liang Ma, Da Wei Huang, Pavel P. Khil, John P. Dekker, Geetha Kutty, Lisa Bishop, Yueqin Liu, Xilong Deng, Philippe M. Hauser, Marco Pagni, Vanessa Hirsch, Richard A. Lempicki, Jason E. Stajich, Christina A. Cuomo, Joseph A. Kovacs
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	evolutionary biology genetic diversity genetic recombination pneumonia population structure Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c0995cfe69d144e9b577c9ecad070400
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spelling	oai:doaj.org-article:c0995cfe69d144e9b577c9ecad0704002021-11-15T16:00:26ZComparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>10.1128/mBio.00381-182150-7511https://doaj.org/article/c0995cfe69d144e9b577c9ecad0704002018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00381-18https://doaj.org/toc/2150-7511ABSTRACT 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.Ousmane H. CisséLiang MaDa Wei HuangPavel P. KhilJohn P. DekkerGeetha KuttyLisa BishopYueqin LiuXilong DengPhilippe M. HauserMarco PagniVanessa HirschRichard A. LempickiJason E. StajichChristina A. CuomoJoseph A. KovacsAmerican Society for Microbiologyarticleevolutionary biologygenetic diversitygenetic recombinationpneumoniapopulation structureMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	evolutionary biology genetic diversity genetic recombination pneumonia population structure Microbiology QR1-502
spellingShingle	evolutionary biology genetic diversity genetic recombination pneumonia population structure Microbiology QR1-502 Ousmane H. Cissé Liang Ma Da Wei Huang Pavel P. Khil John P. Dekker Geetha Kutty Lisa Bishop Yueqin Liu Xilong Deng Philippe M. Hauser Marco Pagni Vanessa Hirsch Richard A. Lempicki Jason E. Stajich Christina A. Cuomo Joseph A. Kovacs Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>
description	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.
format	article
author	Ousmane H. Cissé Liang Ma Da Wei Huang Pavel P. Khil John P. Dekker Geetha Kutty Lisa Bishop Yueqin Liu Xilong Deng Philippe M. Hauser Marco Pagni Vanessa Hirsch Richard A. Lempicki Jason E. Stajich Christina A. Cuomo Joseph A. Kovacs
author_facet	Ousmane H. Cissé Liang Ma Da Wei Huang Pavel P. Khil John P. Dekker Geetha Kutty Lisa Bishop Yueqin Liu Xilong Deng Philippe M. Hauser Marco Pagni Vanessa Hirsch Richard A. Lempicki Jason E. Stajich Christina A. Cuomo Joseph A. Kovacs
author_sort	Ousmane H. Cissé
title	Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>
title_short	Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>
title_full	Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>
title_fullStr	Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>
title_full_unstemmed	Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>
title_sort	comparative population genomics analysis of the mammalian fungal pathogen <italic toggle="yes">pneumocystis</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/c0995cfe69d144e9b577c9ecad070400
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Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen <italic toggle="yes">Pneumocystis</italic>

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