Ape parasite origins of human malaria virulence genes

Daniel B. Larremore, Sesh A. Sundararaman, Weimin Liu, William R. Proto, Aaron Clauset, Dorothy E. Loy, Sheri Speede, Lindsey J. Plenderleith, Paul M. Sharp, Beatrice H. Hahn, Julian C. Rayner and Caroline O. Buckee ()
Additional contact information
Daniel B. Larremore: Center for Communicable Disease Dynamics, Harvard School of Public Health
Sesh A. Sundararaman: Perelman School of Medicine, University of Pennsylvania
Weimin Liu: Perelman School of Medicine, University of Pennsylvania
William R. Proto: Sanger Institute Malaria Programme, The Wellcome Trust Sanger Institute
Aaron Clauset: University of Colorado
Dorothy E. Loy: Perelman School of Medicine, University of Pennsylvania
Sheri Speede: Sanaga-Yong Chimpanzee Rescue Center, IDA-Africa
Lindsey J. Plenderleith: Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh
Paul M. Sharp: Institute of Evolutionary Biology and Centre for Immunity, Infection and Evolution, University of Edinburgh
Beatrice H. Hahn: Perelman School of Medicine, University of Pennsylvania
Julian C. Rayner: Sanger Institute Malaria Programme, The Wellcome Trust Sanger Institute
Caroline O. Buckee: Center for Communicable Disease Dynamics, Harvard School of Public Health

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9368

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