title: Ape parasite origins of human malaria virulence genes.
abstract: Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum.
authors.affiliation: Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.|Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Larremore
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sesh A
authors.initials: SA
authors.lastname: Sundararaman
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Sanger Institute Malaria Programme, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: William R
authors.initials: WR
authors.lastname: Proto
authors.affiliation: Department of Computer Science, University of Colorado, Boulder, Colorado 80309, USA.|Santa Fe Institute, Santa Fe, New Mexico 87501, USA.|BioFrontiers Institute, University of Colorado, Boulder, Colorado 80303, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Clauset
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Loy
authors.affiliation: Sanaga-Yong Chimpanzee Rescue Center, IDA-Africa, Portland, Oregon 97204, USA.
authors.forename: Sheri
authors.initials: S
authors.lastname: Speede
authors.affiliation: Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Lindsey J
authors.initials: LJ
authors.lastname: Plenderleith
authors.affiliation: Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh EH9 3JT, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sharp
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Sanger Institute Malaria Programme, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.affiliation: Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.|Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Buckee
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D006071:Gorilla gorilla / Q000469:parasitology*; D006790:Host-Parasite Interactions / Q000235:genetics*; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000469:parasitology*; D010961:Plasmodium / Q000235:genetics* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D026801:Synteny
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum