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Telomeric expression sites are highly conserved in Trypanosoma brucei.

Hertz-Fowler C, Figueiredo LM, Quail MA, Becker M, Jackson A, Bason N, Brooks K, Churcher C, Fahkro S, Goodhead I, Heath P, Kartvelishvili M, Mungall K, Harris D, Hauser H, Sanders M, Saunders D, Seeger K, Sharp S, Taylor JE, Walker D, White B, Young R, Cross GA, Rudenko G, Barry JD, Louis EJ, Berriman M - PLoS ONE (2008)

Bottom Line: Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs).Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire.This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom. chf@sanger.ac.uk

ABSTRACT
Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

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Overview of T. brucei Lister 427 BES.BES are drawn to scale and have been aligned at their 5′-most ESAG7 or ESAG6 sequence. The inset shows the regions conserved between the dual promoters present in some of the clones. The VSG indicated in front of the BES label refers to the telomere-proximal VSG.
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pone-0003527-g003: Overview of T. brucei Lister 427 BES.BES are drawn to scale and have been aligned at their 5′-most ESAG7 or ESAG6 sequence. The inset shows the regions conserved between the dual promoters present in some of the clones. The VSG indicated in front of the BES label refers to the telomere-proximal VSG.

Mentions: Nineteen TAR clones [19] were sequenced, manually finished and analysed. This set represents 14 unique BESs, with TAR clones from BESs 9 and 16 having been re-classified (Table 2). For each BES group, at least one clone was sequenced (Figure 3, Table 1), choosing a larger sized clone wherever possible. Additional clones were sequenced for BES3 and BES4 to verify the sequence and clone integrity. Global alignments showed that TAR clones 2 and 15 (BES3) as well as 3 and 28 (BES4) are 100% identical at the DNA level with the exception of an ESAG7 triplication in TAR28. In addition, TAR clones from BES1 (TAR40), BES2 (TAR129) and BES17 (TAR59) were compared to the same BES previously sequenced from a BAC library [27] and were 99%,100% and 99% identical, respectively, indicating that TAR cloning produced stable clones.


Telomeric expression sites are highly conserved in Trypanosoma brucei.

Hertz-Fowler C, Figueiredo LM, Quail MA, Becker M, Jackson A, Bason N, Brooks K, Churcher C, Fahkro S, Goodhead I, Heath P, Kartvelishvili M, Mungall K, Harris D, Hauser H, Sanders M, Saunders D, Seeger K, Sharp S, Taylor JE, Walker D, White B, Young R, Cross GA, Rudenko G, Barry JD, Louis EJ, Berriman M - PLoS ONE (2008)

Overview of T. brucei Lister 427 BES.BES are drawn to scale and have been aligned at their 5′-most ESAG7 or ESAG6 sequence. The inset shows the regions conserved between the dual promoters present in some of the clones. The VSG indicated in front of the BES label refers to the telomere-proximal VSG.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2567434&req=5

pone-0003527-g003: Overview of T. brucei Lister 427 BES.BES are drawn to scale and have been aligned at their 5′-most ESAG7 or ESAG6 sequence. The inset shows the regions conserved between the dual promoters present in some of the clones. The VSG indicated in front of the BES label refers to the telomere-proximal VSG.
Mentions: Nineteen TAR clones [19] were sequenced, manually finished and analysed. This set represents 14 unique BESs, with TAR clones from BESs 9 and 16 having been re-classified (Table 2). For each BES group, at least one clone was sequenced (Figure 3, Table 1), choosing a larger sized clone wherever possible. Additional clones were sequenced for BES3 and BES4 to verify the sequence and clone integrity. Global alignments showed that TAR clones 2 and 15 (BES3) as well as 3 and 28 (BES4) are 100% identical at the DNA level with the exception of an ESAG7 triplication in TAR28. In addition, TAR clones from BES1 (TAR40), BES2 (TAR129) and BES17 (TAR59) were compared to the same BES previously sequenced from a BAC library [27] and were 99%,100% and 99% identical, respectively, indicating that TAR cloning produced stable clones.

Bottom Line: Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs).Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire.This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom. chf@sanger.ac.uk

ABSTRACT
Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

Show MeSH
Related in: MedlinePlus