Abstract
Leishmania major is a flagellated protozoan parasite of medical importance. Like other members of the Trypanosomatidae family, it possesses unique mechanisms of gene expression such as constitutive polycistronic transcription of directional gene clusters, gene amplification, mRNA trans-splicing, and extensive editing of mitochondrial transcripts. The molecular signals underlying most of these processes remain under investigation. In order to investigate the role of DNA secondary structure signals in gene expression, we carried out a genome-wide in silico analysis of the intrinsic DNA curvature. The L. major genome revealed a lower frequency of high intrinsic curvature regions as well as inter- and intra- chromosomal distribution heterogeneity, when compared to prokaryotic and eukaryotic organisms. Using a novel method aimed at detecting region-integrated intrinsic curvature (RIIC), high DNA curvature was found to be associated with regions implicated in transcription initiation. Those include divergent strand-switch regions between directional gene clusters and regions linked to markers of active transcription initiation such as acetylated H3 histone, TRF4 and SNAP50. These findings suggest a role for DNA curvature in transcription initiation in Leishmania supporting the relevance of DNA secondary structures signals.
Highlights
Leishmania is a flagellated protozoan parasite of significant medical importance in tropical and subtropical regions of the world
Intrinsic Curvature Distribution in the L. major Genome In order to characterize the secondary structure of the Leishmania genomic sequences, an analysis of the intrinsic curvature distribution was carried out using the bend.it algorithm
Following the completion of the genome sequencing of the Tritryps [47,48,49], genome wide approaches in L. major have been mainly aimed at the characterization of global gene and protein expression profiles during development and in response to drugs, as well as protein subcellular localization, and host-parasite interactions [18,50,51,52,53,54,55,56,57,58,59]
Summary
Leishmania is a flagellated protozoan parasite (order Kinetoplastida) of significant medical importance in tropical and subtropical regions of the world. The numerous human-infective Leishmania species cause a spectrum of diseases known as leishmaniasis, ranging from asymptomatic to lethal infection of internal organs. Leishmania and other members of the Trypanosomatidae family possess unique mechanisms of gene expression, little is known about the nucleic acid signals driving them [2]. No precise element participating in chromosome replication, segregation and mitotic stability has been described in Leishmania, sequences with similarity to the yeast autonomously replicating consensus sequence and centromere DNA elements have been detected in L. donovani [3]. Repeated sequences (direct or inverted) involved in DNA rearrangements, alteration of gene copy number (deletion or amplification), formation of extrachromosomal circular or linear amplicons and supernumerary chromosomes have been described in Leishmania [5,6]. Retroposon traces have been reported [7,8,9] and their involvement in mRNA instability and in the control of transcription initiation have been proposed [10]
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