eprintid: 94796 rev_number: 36 eprint_status: archive userid: 15745 dir: disk0/00/09/47/96 datestamp: 2014-07-02 09:58:41 lastmod: 2025-05-02 02:30:51 status_changed: 2014-07-02 09:58:41 type: article metadata_visibility: show creators_name: Capewell, Paul creators_name: Cooper, Anneli creators_name: Clucas, Caroline creators_name: Weir, William creators_name: MacLeod, Annette creators_orcid: 0000-0002-8803-5034 creators_orcid: 0000-0002-1159-142X creators_orcid: 0000-0001-5592-6810 creators_orcid: 0000-0001-8648-666X creators_orcid: 0000-0002-0150-5049 title: A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome ispublished: pub divisions: 20300000 abstract: <i>Trypanosoma brucei</i> is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other <i>catarrhine</i> primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of <i>T. Brucei</i> have evolved specific mechanisms to overcome this innate resistance, <i>Trypanosoma brucei gambiense</i> and <i>Trypanosoma brucei rhodesiense</i>. In <i>T. b. Rhodesiense</i>, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of <i>T. b. Gambiense</i> is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, <i>T. b. Gambiense</i>-specific glycoprotein <i>(TgsGP)</i>. In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by <i>T. b. Gambiense</i> and <i>T. b. Rhodesiense</i>, with several populations of humans and primates displaying resistance to infection by these two sub-species. date: 2015-02 date_type: published publisher: Cambridge University Press id_number: 10.1017/S0031182014000602 copyright_holders: Copyright © 2014 Cambridge University Press prior: First published in Parasitology 142(S1)108-119 repro: Reproduced under a Creative Commons License uniqueid: glaseprints:2015-94796 published_online: 2014-06-26 issn_online: 1469-8161 funding_project_code: 37179 funding_project_code: 37179 funding_award_no: 6 funding_award_no: 8 funding_project_name: The Wellcome Centre for Molecular Parasitology ( Core Support ) funding_project_name: The Wellcome Centre for Molecular Parasitology ( Core Support ) funding_investigator_name: Andrew Waters funding_investigator_name: Andrew Waters funding_funder_name: Wellcome Trust (WELLCOME) funding_funder_name: Wellcome Trust (WELLCOME) funding_funder_code: 085349/Z/08/Z funding_funder_code: 085349/B/08/Z funding_investigator_dept: III - PARASITOLOGY funding_investigator_dept: III - PARASITOLOGY pubmed_id: 25656360 euro_pubmed_id: 25656360 pmcid: PMC4413828 legacy_divisions: L25000000 full_text_status: public publication: Parasitology volume: 142 number: S1 pagerange: S108-S119 refereed: TRUE issn: 0031-1820 hoa_compliant: 501 hoa_date_pub: 2015-02 hoa_date_fcd: 2015-12-15 hoa_date_foa: 2015-12-15 hoa_version_fcd: VoR hoa_exclude: FALSE hoa_gold: FALSE citation: Capewell, Paul , Cooper, Anneli , Clucas, Caroline , Weir, William and MacLeod, Annette (2015) A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome. Parasitology , 142(S1), S108-S119. (doi: 10.1017/S0031182014000602 ) (PMID:25656360) (PMCID:PMC4413828) document_url: https://eprints.gla.ac.uk/94796/1/94796.pdf