TY - JOUR
T1 - The structure of a conserved telomeric region associated with variant antigen loci in the blood parasite trypanosoma congolense
AU - Abbas, Ali Hadi
AU - Pereira, Sara Silva
AU - D'Archivio, Simon
AU - Wickstead, Bill
AU - Morrison, Liam J.
AU - Hall, Neil
AU - Hertz-Fowler, Christiane
AU - Darby, Alistair C.
AU - Jackson, Andrew P.
N1 - Funding Information:
We would like to thank Dr Jane Munday (University of Glasgow) for preparation of the T. congolense IL3000 DNA. A.H.A. would like to acknowledge the Iraqi Ministry of Higher Education and Scientific Research/University of Kufa/Faculty of Veterinary Medicine for funding part of this research. This work was supported by a Grand Challenges (Round 11) award from the Bill and Melinda Gates Foundation and a Biotechnology and Biological Sciences Research Council (BBSRC) New investigator Award (BB/M022811/1) to A.P.J.; by Iraqi Ministry of Higher Education and Scientific Research/ Iraqi Cultural Attaché’ Award (977) awarded to A.C.D. and A.H.A.; and by BBSRC New Investigator Award (BB/ J01477X/1) to B.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - African trypanosomiasis is a vector-borne disease of humans and livestock caused by African trypanosomes (Trypanosoma spp.). Survival in the vertebrate bloodstream depends on antigenic variation of Variant Surface Glycoproteins (VSGs) coating the parasite surface. In T. brucei, a model for antigenic variation, monoallelic VSG expression originates from dedicated VSG expression sites (VES). Trypanosoma brucei VES have a conserved structure consisting of a telomeric VSG locus downstream of unique, repeat sequences, and an independent promoter. Additional protein-coding sequences, known as "Expression Site Associated Genes (ESAGs)", are also often present and are implicated in diverse, bloodstream-stage functions. Trypanosoma congolense is a related veterinary pathogen, also displaying VSG-mediated antigenic variation. A T. congolense VES has not been described, making it unclear if regulation of VSG expression is conserved between species. Here, we describe a conserved telomeric region associated with VSG loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; although these are not orthologous to T. brucei ESAGs. Most conserved telomeric regions are associated with accessory minichromosomes, but the same structure may also be associated with megabase chromosomes. We propose that this region represents the T. congolense VES, and through comparison with T. brucei, we discuss the parallel evolution of antigenic switching mechanisms, and unique adaptation of the T. brucei VES for developmental regulation of bloodstream-stage genes. Hence, we provide a basis for understanding antigenic switching in T. congolense and the origins of the African trypanosome VES.
AB - African trypanosomiasis is a vector-borne disease of humans and livestock caused by African trypanosomes (Trypanosoma spp.). Survival in the vertebrate bloodstream depends on antigenic variation of Variant Surface Glycoproteins (VSGs) coating the parasite surface. In T. brucei, a model for antigenic variation, monoallelic VSG expression originates from dedicated VSG expression sites (VES). Trypanosoma brucei VES have a conserved structure consisting of a telomeric VSG locus downstream of unique, repeat sequences, and an independent promoter. Additional protein-coding sequences, known as "Expression Site Associated Genes (ESAGs)", are also often present and are implicated in diverse, bloodstream-stage functions. Trypanosoma congolense is a related veterinary pathogen, also displaying VSG-mediated antigenic variation. A T. congolense VES has not been described, making it unclear if regulation of VSG expression is conserved between species. Here, we describe a conserved telomeric region associated with VSG loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; although these are not orthologous to T. brucei ESAGs. Most conserved telomeric regions are associated with accessory minichromosomes, but the same structure may also be associated with megabase chromosomes. We propose that this region represents the T. congolense VES, and through comparison with T. brucei, we discuss the parallel evolution of antigenic switching mechanisms, and unique adaptation of the T. brucei VES for developmental regulation of bloodstream-stage genes. Hence, we provide a basis for understanding antigenic switching in T. congolense and the origins of the African trypanosome VES.
KW - Antigenic variation
KW - ESAG
KW - Expression site
KW - Telomere
KW - Trypanosoma congolense
KW - Variant surface glycoprotein
UR - http://www.scopus.com/inward/record.url?scp=85054093634&partnerID=8YFLogxK
U2 - 10.1093/gbe/evy186
DO - 10.1093/gbe/evy186
M3 - Article
C2 - 30165630
SN - 1759-6653
VL - 10
SP - 2458
EP - 2473
JO - Genome Biology and Evolution
JF - Genome Biology and Evolution
IS - 9
ER -