title: A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome.
abstract: Trypanosoma brucei 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 catarrhine 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 T. brucei have evolved specific mechanisms to overcome this innate resistance, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. In T. b. rhodesiense, 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 T. b. gambiense 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, T. b. gambiense-specific glycoprotein (TgsGP). In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b. gambiense and T. b. rhodesiense, with several populations of humans and primates displaying resistance to infection by these two sub-species.
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences,University of Glasgow,464 Bearsden Road, Glasgow G61 1QH,UK.
authors: Paul
authors: P
authors: Capewell
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences,University of Glasgow,464 Bearsden Road, Glasgow G61 1QH,UK.
authors: Anneli
authors: A
authors: Cooper
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences,University of Glasgow,464 Bearsden Road, Glasgow G61 1QH,UK.
authors: Caroline
authors: C
authors: Clucas
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences,University of Glasgow,464 Bearsden Road, Glasgow G61 1QH,UK.
authors: William
authors: W
authors: Weir
authors: Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences,University of Glasgow,464 Bearsden Road, Glasgow G61 1QH,UK.
authors: Annette
authors: A
authors: Macleod
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D005075:Biological Evolution; D015894:Genome, Human / Q000235:genetics*; D018503:Genome, Protozoan / Q000235:genetics*; D006790:Host-Parasite Interactions; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics; D044967:Serum / Q000469:parasitology; D014346:Trypanosoma brucei brucei / Q000235:genetics*; D014347:Trypanosoma brucei gambiense / Q000235:genetics*; D016833:Trypanosoma brucei rhodesiense / Q000235:genetics*; D014353:Trypanosomiasis, African / Q000469:parasitology*
chemical_list: D001053:Apolipoproteins; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins
keywords: Trypanosome
references: Curr Opin Microbiol. 2001 Aug;4(4):402-8
references: 11495802
references: PLoS Negl Trop Dis. 2010;4(4):e658
references: 20404998
references: J Am Soc Nephrol. 2010 Sep;21(9):1422-6
references: 20688934
references: Nat Med. 2006 May;12(5):580-4
references: 16604085
references: Autophagy. 2008 Nov;4(8):1079-82
references: 18927493
references: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13442-7
references: 11078512
references: Lancet. 2001 Dec 15;358(9298):2017-9
references: 11755607
references: Tropenmed Parasitol. 1981 Sep;32(3):129-33
references: 6285559
references: Nature. 2003 Mar 6;422(6927):83-7
references: 12621437
references: J Biol Chem. 2010 Sep 10;285(37):28659-66
references: 20615879
references: Ann Soc Belg Med Trop. 1992;72 Suppl 1:13-21
references: 1417165
references: Trends Parasitol. 2006 Sep;22(9):405-9
references: 16837245
references: Infect Genet Evol. 2010 May;10(4):453-8
references: 20302972
references: PLoS Negl Trop Dis. 2011;5(2):e1007
references: 21364972
references: Am J Trop Med Hyg. 2002 Dec;67(6):684-90
references: 12518862
references: PLoS Negl Trop Dis. 2011;5(2):e961
references: 21347445
references: J Biol Chem. 2001 Aug 10;276(32):30254-60
references: 11352898
references: Infect Genet Evol. 2002 May;1(3):207-14
references: 12798017
references: Parasitol Today. 1986 Sep;2(9):255-7
references: 15462856
references: Proc Natl Acad Sci U S A. 1978 Jul;75(7):3450-4
references: 210461
references: Exp Parasitol. 1978 Dec;46(2):189-206
references: 83247
references: Nat Rev Microbiol. 2006 Jun;4(6):477-86
references: 16710327
references: PLoS Negl Trop Dis. 2013 Nov;7(11):e2526
references: 24244771
references: PLoS Negl Trop Dis. 2009 Sep 01;3(9):e509
references: 19721701
references: PLoS Negl Trop Dis. 2012;6(6):e1691
references: 22720107
references: Am J Hum Genet. 2013 Jul 11;93(1):54-66
references: 23768513
references: Genome Res. 2009 May;19(5):850-8
references: 19299565
references: Int J Parasitol. 2010 Feb;40(2):149-56
references: 19968994
references: Hum Genet. 2010 Sep;128(3):345-50
references: 20635188
references: Int J Parasitol. 2004 Jul;34(8):887-98
references: 15217727
references: J Biol Chem. 1997 Oct 10;272(41):25576-82
references: 9325276
references: Mol Biochem Parasitol. 2001 Apr 25;114(1):1-16
references: 11356509
references: Mol Biochem Parasitol. 1994 Aug;66(2):211-20
references: 7808471
references: Tropenmed Parasitol. 1981 Sep;32(3):134-40
references: 6285560
references: Trends Parasitol. 2002 Nov;18(11):486-90
references: 12473364
references: Adv Parasitol. 2001;49:1-70
references: 11461029
references: Mol Biochem Parasitol. 2003 Mar;127(1):79-84
references: 12615339
references: Parasitology. 2005 Aug;131(Pt 2):143-50
references: 16145931
references: Ann N Y Acad Sci. 2006 Oct;1081:311-9
references: 17135530
references: PLoS Negl Trop Dis. 2011 Sep;5(9):e1287
references: 21909441
references: Trop Med Int Health. 2005 Sep;10(9):840-9
references: 16135190
references: Infect Genet Evol. 2007 Jan;7(1):60-8
references: 16720107
references: J Biol Chem. 2008 Aug 1;283(31):21540-9
references: 18505729
references: Science. 2010 Aug 13;329(5993):841-5
references: 20647424
references: Ann Soc Belg Med Trop. 1976;56(1):55-63
references: 1015880
references: Mol Biochem Parasitol. 1999 Nov 30;104(2):271-83
references: 10593181
references: Am J Trop Med Hyg. 2007 May;76(5):922-9
references: 17488917
references: PLoS Negl Trop Dis. 2013;7(3):e2121
references: 23556014
references: Virulence. 2012 Jan-Feb;3(1):72-6
references: 22286709
references: Mol Biochem Parasitol. 1989 Sep;36(2):169-76
references: 2528066
references: Parasitology. 1994 Jul;109 ( Pt 1):95-111
references: 7914692
references: Infect Genet Evol. 2012 Oct;12(7):1519-23
references: 22691369
references: PLoS Pathog. 2007 Sep 28;3(9):1250-61
references: 17845074
references: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4118-23
references: 17360487
references: Hum Genet. 2014 Jan;133(1):69-83
references: 24005574
references: Mol Biochem Parasitol. 2004 Nov;138(1):9-20
references: 15500911
references: Exp Parasitol. 1991 May;72(4):430-9
references: 2026217
references: Cell Mol Life Sci. 2006 Sep;63(17):1937-44
references: 16847577
references: PLoS Negl Trop Dis. 2012;6(7):e1728
references: 22802982
references: Tropenmed Parasitol. 1984 Jun;35(2):105-8
references: 6464184
references: PLoS Pathog. 2013;9(4):e1003317
references: 23637606
references: Science. 2008 May 2;320(5876):677-81
references: 18451305
references: Tropenmed Parasitol. 1982 Jun;33(2):113-8
references: 6287687
references: J Biol Chem. 1989 Mar 25;264(9):5210-7
references: 2494183
references: Tropenmed Parasitol. 1978 Sep;29(3):335-45
references: 726046
references: Mol Biochem Parasitol. 2001 Mar;113(1):127-38
references: 11254961
references: Mol Biochem Parasitol. 1995 Mar;70(1-2):131-8
references: 7637693
references: Mol Biochem Parasitol. 1994 Dec;68(2):277-84
references: 7739673
references: Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16137-41
references: 20805508
references: Cell. 1998 Dec 11;95(6):839-46
references: 9865701
references: J Protozool. 1990 Sep-Oct;37(5):393-400
references: 2120433
references: Tropenmed Parasitol. 1979 Jun;30(2):212-9
references: 483383
references: Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1905-10
references: 23319650
references: J Biol Chem. 2008 Oct 24;283(43):28934-43
references: 18701454
references: Mol Biochem Parasitol. 2001 Nov;118(1):33-40
references: 11704271
references: J Eukaryot Microbiol. 2007 Jan-Feb;54(1):18-21
references: 17300512
references: Lancet. 2001 Aug 25;358(9282):625-8
references: 11530149
references: J Cell Biol. 1994 Jul;126(1):155-67
references: 8027174
references: J Infect Dis. 2005 Jul 1;192(1):178-86
references: 15942909
references: Nature. 2013 Sep 19;501(7467):430-4
references: 23965626
references: Ann Soc Belg Med Trop. 1991 Mar;71(1):39-46
references: 2042999
references: J Biol Chem. 2003 Jan 3;278(1):422-7
references: 12401813
references: Infect Genet Evol. 2006 Mar;6(2):123-9
references: 15894515
references: Adv Parasitol. 1980;18:175-246
references: 7001872
references: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4680-5
references: 11930015
references: Lancet. 2005 Aug 27-Sep 2;366(9487):745-7
references: 16125592
references: PLoS Pathog. 2009 Dec;5(12):e1000685
references: 19997494
references: Biochem Soc Trans. 2000 Feb;28(2):51-6
references: 10816098
references: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19509-14
references: 19858474
references: Infect Immun. 2004 Dec;72(12):7040-4
references: 15557627
references: Mol Microbiol. 2010 May;76(4):806-14
references: 20398209
references: Eukaryot Cell. 2006 Jan;5(1):132-9
references: 16400175
references: PLoS Pathog. 2013;9(10):e1003686
references: 24098129
references: J Exp Med. 1996 Mar 1;183(3):1023-9
references: 8642243
references: Science. 2005 Jul 15;309(5733):416-22
references: 16020726