TY - JOUR
T1 - The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction
AU - Jackson, Andrew P.
AU - Otto, Thomas D.
AU - Darby, Alistair
AU - Ramaprasad, Abhinay
AU - Xia, Dong
AU - Echaide, Ignacio Eduardo
AU - Farber, Marisa
AU - Gahlot, Sunayna
AU - Gamble, John
AU - Gupta, Dinesh
AU - Gupta, Yask
AU - Jackson, Louise
AU - Malandrin, Laurence
AU - Malas, Tareq Majed Yasin
AU - Moussa, Ehab
AU - Nair, Mridul
AU - Reid, Adam J.
AU - Sanders, Mandy
AU - Sharma, Jyotsna
AU - Tracey, Alan
AU - Quail, Mike A.
AU - Weir, William
AU - Wastling, Jonathan M.
AU - Hall, Neil
AU - Willadsen, Peter
AU - Lingelbach, Klaus
AU - Shiels, Brian
AU - Tait, Andy
AU - Berriman, Matt
AU - Allred, David R.
AU - Pain, Arnab
N1 - KAUST Repository Item: Exported on 2020-10-01
PY - 2014/5/5
Y1 - 2014/5/5
N2 - 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. 2014 The Author(s) 2014.
AB - 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. 2014 The Author(s) 2014.
UR - http://hdl.handle.net/10754/325457
UR - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gku322
UR - http://www.scopus.com/inward/record.url?scp=84903183110&partnerID=8YFLogxK
U2 - 10.1093/nar/gku322
DO - 10.1093/nar/gku322
M3 - Article
C2 - 24799432
SN - 1362-4962
VL - 42
SP - 7113
EP - 7131
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 11
ER -