A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome.
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TLDR
In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b.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.read more
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References
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Journal ArticleDOI
The Genome of the African Trypanosome Trypanosoma brucei
Matthew Berriman,Elodie Ghedin,Elodie Ghedin,Christiane Hertz-Fowler,Gaëlle Blandin,Hubert Renauld,Daniella Castanheira Bartholomeu,Nicola Lennard,Elisabet Caler,N. Hamlin,Brian J. Haas,Ulrike Böhme,Linda Hannick,Martin Aslett,Joshua Shallom,Lucio Marcello,Lihua Hou,Bill Wickstead,U. Cecilia M. Alsmark,Claire Arrowsmith,Rebecca Atkin,Andrew Barron,Frédéric Bringaud,Karen Brooks,Mark Carrington,Inna Cherevach,Tracey-Jane Chillingworth,Carol Churcher,Louise Clark,Craig Corton,Ann Cronin,Robert L. Davies,Jonathon Doggett,Appolinaire Djikeng,Tamara Feldblyum,Mark C. Field,Audrey Fraser,Ian Goodhead,Zahra Hance,David Harper,Barbara Harris,Heidi Hauser,Jessica B. Hostetler,Al Ivens,Kay Jagels,David W. Johnson,Justin Johnson,Kristine Jones,Arnaud Kerhornou,Hean Koo,Natasha Larke,Scott M. Landfear,Christopher Larkin,Vanessa Leech,Alexandra Line,Angela Lord,Annette MacLeod,P. Mooney,Sharon Moule,David M. A. Martin,Gareth W. Morgan,Karen Mungall,Halina Norbertczak,Doug Ormond,Grace Pai,Christopher S. Peacock,Jeremy Peterson,Michael A. Quail,Ester Rabbinowitsch,Marie-Adèle Rajandream,Chris P Reitter,Steven L. Salzberg,Mandy Sanders,Seth Schobel,Sarah Sharp,Mark Simmonds,Anjana J. Simpson,Luke J. Tallon,C. Michael R. Turner,Andrew Tait,Adrian Tivey,Susan Van Aken,Danielle Walker,David Wanless,Shiliang Wang,Brian White,Owen White,Sally Whitehead,John Woodward,Jennifer R. Wortman,Mark Raymond Adams,T. Martin Embley,Keith Gull,Elisabetta Ullu,J. David Barry,Alan H. Fairlamb,Fred R. Opperdoes,Barclay G. Barrell,John E. Donelson,Neil Hall,Neil Hall,Claire M. Fraser,Sara E. Melville,Najib M. El-Sayed,Najib M. El-Sayed +104 more
TL;DR: Comparisons of the cytoskeleton and endocytic trafficking systems of Trypanosoma brucei with those of humans and other eukaryotic organisms reveal major differences.
Journal ArticleDOI
Association of trypanolytic ApoL1 variants with kidney disease in African Americans.
Giulio Genovese,Giulio Genovese,David J. Friedman,Michael D. Ross,Laurence Lecordier,Pierrick Uzureau,Barry I. Freedman,Donald W. Bowden,Carl D. Langefeld,Taras K. Oleksyk,Andrea L. Uscinski Knob,Andrea J. Bernhardy,Pamela J. Hicks,George W. Nelson,Benoit Vanhollebeke,Cheryl A. Winkler,Jeffrey B. Kopp,Etienne Pays,Martin R. Pollak,Martin R. Pollak +19 more
TL;DR: This article showed that focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22.
Association of Trypanolytic ApoL1 Variants with Kidney Disease in
Giulio Genovese,David J. Friedman,Michael W. Ross,Laurence Lecordier,Pierrick Uzureau,Barry I. Freedman,Donald W. Bowden,Carl D. Langefeld,Taras K. Oleksyk,Andrea L. Uscinski Knob,Andrea J. Bernhardy,Pamela J. Hicks,George W. Nelson,Benoit Vanhollebeke,Cheryl A. Winkler,Jeffrey B. Kopp,Etienne Pays,Martin R. Pollak +17 more
TL;DR: In African Americans, focal segmental glomerulosclerosis and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22, which speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.
Journal ArticleDOI
Neglected tropical diseases
TL;DR: Although there are proven strategies to control several NTDs, these diseases continue to cause a massive burden of morbidity and there is urgent need for more basic and operational research, drug and vaccine development, and greater prioritization by governments and international agencies.
Journal ArticleDOI
Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene
Shay Tzur,Saharon Rosset,Revital Shemer,Guennady Yudkovsky,Sara Selig,Ayele Tarekegn,Ayele Tarekegn,Endashaw Bekele,Neil Bradman,Walter G. Wasser,Doron M. Behar,Karl Skorecki +11 more
TL;DR: This work uses recently released sequences from the 1000 Genomes Project to identify two western African-specific missense mutations in the neighboring APOL1 gene, and demonstrates that these are more strongly associated with ESKD than previously reported MYH9 variants.
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