TY - JOUR T1 - Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania. JF - PLoS Pathog Y1 - 2007 A1 - Bringaud, Frederic A1 - Müller, Michaela A1 - Cerqueira, Gustavo Coutinho A1 - Smith, Martin A1 - Rochette, Annie A1 - el-Sayed, Najib M A A1 - Papadopoulou, Barbara A1 - Ghedin, Elodie KW - 3' Untranslated Regions KW - Animals KW - Base Sequence KW - Biological Evolution KW - Down-Regulation KW - Gene Expression Regulation KW - Genome, Protozoan KW - Leishmania KW - Leishmania major KW - Molecular Sequence Data KW - Retroelements KW - RNA, Messenger KW - sequence alignment KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi AB -

Trypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis), Trypanosoma brucei (sleeping sickness), and Trypanosoma cruzi (Chagas disease). Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements--LmSIDER1 (785 copies) and LmSIDER2 (1,073 copies)--that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are approximately 70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3'-untranslated regions (3'UTRs) of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3'UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function.

VL - 3 CP - 9 M3 - 10.1371/journal.ppat.0030136 ER - TY - JOUR T1 - Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2006 A1 - Bringaud, Frederic A1 - Ghedin, Elodie A1 - Blandin, Gaëlle A1 - Bartholomeu, Daniella C. A1 - Caler, Elisabet A1 - Levin, Mariano J. A1 - Baltz, Théo A1 - Najib M. El‐Sayed KW - Degenerate retroelement KW - Evolution KW - Ingi KW - L1Tc KW - Leishmania major KW - Non-LTR retrotransposon KW - Retroposon KW - Trypanosoma brucei KW - Trypanosoma cruzi AB - The ingi and L1Tc non-LTR retrotransposons - which constitute the ingi clade - are abundant in the genome of the trypanosomatid species Trypanosoma brucei and Trypanosoma cruzi, respectively. The corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, Leishmania major. To study the evolution of non-LTR retrotransposons in trypanosomatids, we have analyzed all ingi/L1Tc elements and highly degenerate ingi/L1Tc-related sequences identified in the recently completed T. brucei, T. cruzi and L. major genomes. The coding sequences of 242 degenerate ingi/L1Tc-related elements (DIREs) in all three genomes were reconstituted by removing the numerous frame shifts. Three independent phylogenetic analyses conducted on the conserved domains encoded by these elements show that all DIREs, including the 52 L. major DIREs, form a monophyletic group belonging to the ingi clade. This indicates that the trypanosomatid ancestor contained active mobile elements that have been retained in the Trypanosoma species, but were lost from L. major genome, where only remnants (DIRE) are detectable. All 242 DIREs analyzed group together according to their species origin with the exception of 11 T. cruzi DIREs which are close to the T. brucei ingi/DIRE families. Considering the absence of known horizontal transfer between the African T. brucei and the South-American T. cruzi, this suggests that this group of elements evolved at a lower rate when compared to the other trypanosomatid elements. Interestingly, the only nucleotide sequence conserved between ingi and L1Tc (the first 79 residues) is also present at the 5'-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs. VL - 145 SN - 0166-6851 ER - TY - JOUR T1 - Gene synteny and evolution of genome architecture in trypanosomatids. JF - Mol Biochem Parasitol Y1 - 2004 A1 - Ghedin, Elodie A1 - Bringaud, Frederic A1 - Peterson, Jeremy A1 - Myler, Peter A1 - Berriman, Matthew A1 - Ivens, Alasdair A1 - Andersson, Björn A1 - Bontempi, Esteban A1 - Eisen, Jonathan A1 - Angiuoli, Sam A1 - Wanless, David A1 - Von Arx, Anna A1 - Murphy, Lee A1 - Lennard, Nicola A1 - Salzberg, Steven A1 - Adams, Mark D A1 - White, Owen A1 - Hall, Neil A1 - Stuart, Kenneth A1 - Fraser, Claire M A1 - el-Sayed, Najib M A KW - Animals KW - Computational Biology KW - Evolution, Molecular KW - Gene Order KW - Genome, Protozoan KW - Genomics KW - Leishmania major KW - Multigene Family KW - Recombination, Genetic KW - Retroelements KW - Selection, Genetic KW - Synteny KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi KW - Trypanosomatina AB -

The trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.

VL - 134 CP - 2 M3 - 10.1016/j.molbiopara.2003.11.012 ER -