TY - Generic T1 - Genomic analysis of sequence-dependent DNA curvature in Leishmania. Y1 - 2013 A1 - Smircich, Pablo A1 - Forteza, Diego A1 - El-Sayed, Najib M A1 - Garat, Beatriz KW - Chromosome mapping KW - Comparative Genomic Hybridization KW - Computational Biology KW - DNA, Protozoan KW - Genome, Protozoan KW - Genomics KW - HUMANS KW - Leishmania KW - Nucleic Acid Conformation AB -

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.

JA - PLoS One VL - 8 CP - 4 M3 - 10.1371/journal.pone.0063068 ER - TY - JOUR T1 - The genome and its implications. JF - Adv Parasitol Y1 - 2011 A1 - Teixeira, Santuza M A1 - El-Sayed, Najib M A1 - Araújo, Patrícia R KW - Animals KW - Antigens, Protozoan KW - Chagas Disease KW - Chromosomes KW - Comparative Genomic Hybridization KW - DNA, Protozoan KW - Gene Expression Regulation KW - Genetic Variation KW - Genome, Protozoan KW - Host-Parasite Interactions KW - HUMANS KW - Species Specificity KW - Synteny KW - Transcription, Genetic KW - Transfection KW - Trypanosoma cruzi AB -

Trypanosoma cruzi has a heterogeneous population composed of a pool of strains that circulate in the domestic and sylvatic cycles. Genome sequencing of the clone CL Brener revealed a highly repetitive genome of about 110Mb containing an estimated 22,570 genes. Because of its hybrid nature, sequences representing the two haplotypes have been generated. In addition, a repeat content close to 50% made the assembly of the estimated 41 pairs of chromosomes quite challenging. Similar to other trypanosomatids, the organization of T. cruzi chromosomes was found to be very peculiar, with protein-coding genes organized in long polycistronic transcription units encoding 20 or more proteins in one strand separated by strand switch regions. Another remarkable feature of the T. cruzi genome is the massive expansion of surface protein gene families. Because of the high genetic diversity of the T. cruzi population, sequencing of additional strains and comparative genomic and transcriptome analyses are in progress. Five years after its publication, the genome data have proven to be an essential tool for the study of T. cruzi and increasing efforts to translate this knowledge into the development of new modes of intervention to control Chagas disease are underway.

VL - 75 M3 - 10.1016/B978-0-12-385863-4.00010-1 ER -