title: Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes.
abstract: Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure of T. gondii is characterized by clade-specific inheritance of large conserved haploblocks that are significantly enriched in tandemly clustered secretory pathogenesis determinants. The shared inheritance of these conserved haploblocks, which show a different ancestry than the genome as a whole, may thus influence transmission, host range and pathogenicity.
authors.affiliation: Department of Infectious Diseases, The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, Maryland 20850, USA.
authors.forename: Hernan
authors.initials: H
authors.lastname: Lorenzi
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63130, USA.|Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Asis
authors.initials: A
authors.lastname: Khan
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63130, USA.|Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rougea Louisian 70803, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Behnke
authors.affiliation: Department of Genetics, University of Georgia, Athens, Georgia 30602, USA.|Center for Tropical and Emerging Global Diseases, University of Georgia, Athens Georgia 30602, USA.
authors.forename: Sivaranjani
authors.initials: S
authors.lastname: Namasivayam
authors.affiliation: Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1L7.|Departments of Biochemistry and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Lakshmipuram S
authors.initials: LS
authors.lastname: Swapna
authors.affiliation: Department of Infectious Diseases, The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, Maryland 20850, USA.
authors.forename: Michalis
authors.initials: M
authors.lastname: Hadjithomas
authors.affiliation: Department of Infectious Diseases, The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, Maryland 20850, USA.
authors.forename: Svetlana
authors.identifier: http://orcid.org/0000-0001-9653-8910
authors.initials: S
authors.lastname: Karamycheva
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Pinney
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brunk
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: James W
authors.initials: JW
authors.lastname: Ajioka
authors.affiliation: Biological Resource Center for Toxoplasma, INSERM, University Limoges, CHU Limoges, UMR_S 1094, Tropical Neuroepidemiology, Institute of Neuroepidemiology and Tropical Neurology, Limoges 87025, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ajzenberg
authors.affiliation: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, California 94305, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
authors.affiliation: Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Jon P
authors.initials: JP
authors.lastname: Boyle
authors.affiliation: Biological Resource Center for Toxoplasma, INSERM, University Limoges, CHU Limoges, UMR_S 1094, Tropical Neuroepidemiology, Institute of Neuroepidemiology and Tropical Neurology, Limoges 87025, France.
authors.forename: Marie L
authors.initials: ML
authors.lastname: Dardé
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Diaz-Miranda
authors.affiliation: Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, USDA, Beltsville, Maryland 20705, USA.
authors.forename: Jitender P
authors.initials: JP
authors.lastname: Dubey
authors.affiliation: Department of Veterinary Pathology and Microbiology, Washington State University, College of Veterinary Medicine, Pullman, Washington 99164, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Fritz
authors.affiliation: Department of Preventive Veterinary Medicine and Animal Health, Faculty of Veterinary Medicine, University of São Paulo, São Paulo, SP CEP 05598-270, Brazil.
authors.forename: Solange M
authors.initials: SM
authors.lastname: Gennari
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gregory
authors.affiliation: Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Kami
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pathology, Microbiology &Immunology, University of California, David, California 95616, USA.
authors.forename: Jeroen P J
authors.initials: JP
authors.lastname: Saeij
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996, USA.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Su
authors.affiliation: Departments of Molecular Medicine and Global Health, Florida Center for Drug Discovery and Development (CDDI), University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: White
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, China.
authors.forename: Xing-Quan
authors.initials: XQ
authors.lastname: Zhu
authors.affiliation: Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Howe
authors.affiliation: Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, USDA, Beltsville, Maryland 20705, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Rosenthal
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Grigg
authors.affiliation: Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1L7.|Departments of Biochemistry and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: John
authors.initials: J
authors.lastname: Parkinson
authors.affiliation: Department of Statistics, University of Georgia, Athens Georgia 30602, USA.|Institute of Bioinformatics, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Genetics, University of Georgia, Athens, Georgia 30602, USA.|Center for Tropical and Emerging Global Diseases, University of Georgia, Athens Georgia 30602, USA.|Institute of Bioinformatics, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kissinger
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Roos
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63130, USA.
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
mesh_terms: D017124:Conserved Sequence; D016054:DNA, Protozoan / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D018503:Genome, Protozoan; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D026801:Synteny; D014122:Toxoplasma / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; D012333:RNA, Messenger