title: The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.
abstract: Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5' ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.
authors.affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK a.p.jackson@liv.ac.uk.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Jackson
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Otto
authors.affiliation: Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: Alistair
authors.initials: A
authors.lastname: Darby
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Abhinay
authors.initials: A
authors.lastname: Ramaprasad
authors.affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK.
authors.forename: Dong
authors.initials: D
authors.lastname: Xia
authors.affiliation: Laboratorio de Inmunología y , EEA-INTA CC 22, 2300 Rafaela Santa Fe, Argentina.
authors.forename: Ignacio Eduardo
authors.initials: IE
authors.lastname: Echaide
authors.affiliation: Centro Nacional de Investigaciones Agropecuarias, Instituto de Biotecnología INTA, Buenos Aires, Argentina.
authors.forename: Marisa
authors.initials: M
authors.lastname: Farber
authors.affiliation: Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Sunayna
authors.initials: S
authors.lastname: Gahlot
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: John
authors.initials: J
authors.lastname: Gamble
authors.affiliation: Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Bioinformatics Laboratory, Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110 067, India.
authors.forename: Yask
authors.initials: Y
authors.lastname: Gupta
authors.affiliation: Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Jackson
authors.affiliation: UMR1300 INRA/Oniris Biology, Epidemiology and Risk Analysis in Animal Health, BP 40706, F-44307 Nantes, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Malandrin
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Tareq B
authors.initials: TB
authors.lastname: Malas
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Ehab
authors.initials: E
authors.lastname: Moussa
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Mridul
authors.initials: M
authors.lastname: Nair
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Reid
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Mandy
authors.initials: M
authors.lastname: Sanders
authors.affiliation: FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Tracey
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Mike A
authors.initials: MA
authors.lastname: Quail
authors.affiliation: FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany.
authors.forename: William
authors.initials: W
authors.lastname: Weir
authors.affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wastling
authors.affiliation: Department of Functional and Comparative Genomics, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Hall
authors.affiliation: Department of Agriculture, Fisheries and Forestry, Biosecurity Sciences Laboratory, 39 Kessels Road, Coopers Plains, Queensland 4108, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Willadsen
authors.affiliation: FG Parasitologie, Philipps Universität Marburg, Karl von Frisch Strasse 8, 35043 Marburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lingelbach
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Shiels
authors.affiliation: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Tait
authors.affiliation: Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Berriman
authors.affiliation: Department of Infectious Diseases and Pathology, and Genetics Institute, University of Florida, PO Box 110880, 2015 SW 16th Avenue, Gainesville FL 33611-0880, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Allred
authors.affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
mesh_terms: D000940:Antigenic Variation; D001403:Babesia / Q000235:genetics*; D056905:Chromosome Breakpoints; D019143:Evolution, Molecular; D017125:Genes, Protozoan; D018503:Genome, Protozoan; D006790:Host-Parasite Interactions / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics; D011995:Recombination, Genetic
chemical_list: D015800:Protozoan Proteins