Background: Homopolymeric tracts, particularly poly dA.dT, are enriched within the intergenic sequences of eukaryotic genomes where they appear to act as intrinsic regulators of nucleosome positioning. A previous study of the incomplete genome of the human malarial parasite Plasmodium falciparum reports a higher than expected enrichment of poly dA.dT tracts, far above that anticipated even in this highly AT rich genome. Here we report an analysis of the relative frequency, length and spatial arrangement of homopolymer tracts for the complete P. falciparum genome, extending this analysis to twelve additional genomes of Apicomplexan parasites important to human and animal health. In addition, using nucleosome-positioning data available for P. falciparum, we explore the correlation of poly dA.dT tracts with nucleosome-positioning data over key expression landmarks within intergenic regions.
Results: We describe three apparent lineage-specific patterns of homopolymeric tract organization within the intergenic regions of these Apicomplexan parasites. Moreover, a striking pattern of enrichment of overly long poly dA.dT tracts in the intergenic regions of Plasmodium spp. uniquely extends into protein coding sequences. There is a conserved spatial arrangement of poly dA.dT immediately flanking open reading frames and over predicted core promoter sites. These key landmarks are all relatively depleted in nucleosomes in P. falciparum, as would be expected for poly dA.dT acting as nucleosome exclusion sequences.
Conclusions: Previous comparative studies of homopolymer tract organization emphasize evolutionary diversity; this is the first report of such an analysis within a single phylum. Our data provide insights into the evolution of homopolymeric tracts and the selective pressures at play in their maintenance and expansion.
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http://dx.doi.org/10.1186/1471-2164-15-848 | DOI Listing |
J Inorg Biochem
March 2024
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA, UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, (B1906ZAA) La Plata, Argentina. Electronic address:
ACS Omega
February 2023
School of Physical Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
In biological systems, the unprompted assembly of DNA molecules by cationic ligands into condensed structures is ubiquitous. The ability of ligands to provoke DNA packaging is crucial to the molecular organization and functional control of DNA, yet their underlined physical roles have remained elusive. Here, we have examined the DNA condensation mechanism of four cationic ligands, including their primary DNA-binding modes through extensive biophysical studies.
View Article and Find Full Text PDFEur J Med Chem
October 2021
Department of Chemistry, Georgia State University, Atlanta, GA, 30303, Georgia.
Dicationic diamidines have been well established as potent antiparasitic agents with proven activity against tropical diseases like trypanosomiasis and malaria. This work presents the synthesis of new mono and diflexible triaryl amidines (6a-c, 13a,b and 17), their aza analogues (23 and 27) and respective methoxyamidine prodrugs (5, 7, 12a,b, 22 and 26). All diamidines were assessed in vitro against Trypanosoma brucei rhodesiense (T.
View Article and Find Full Text PDFInorg Chem
July 2019
Department of Chemistry and Chemical Engineering , Chalmers University of Technology, Kemigården 4 , SE-412 96 Gothenburg , Sweden.
The biexponential excited-state emission decay characteristic of DNA intercalated tris-bidentate dppz-based ruthenium complexes of the general form Ru(L)dppz has previously been explained by a binding model with two distinct geometry orientations of the bound ligands, with a distinct lifetime associated with each orientation. However, it has been found that upon DNA binding of Ru(phen)dppz the fractions of short and long lifetimes are strongly dependent on environmental factors such as salt concentration and, in particular, temperature. Analyzing isothermal titration calorimetry for competitive binding of Ru(phen)dppz enantiomers to poly(dAdT), we find that a consistent binding model must assume that the short and long lifetimes states of intercalated complexes are in equilibrium and that this equilibrium is altered when neighboring bound ligands affect each other.
View Article and Find Full Text PDFPhys Chem Chem Phys
April 2018
Department of Chemistry and Chemical Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
Isothermal titration calorimetry (ITC) has been utilized to investigate the effect of methyl substituents on the intercalating dppz ligand of the enantiomers of the parent complex Ru(phen)2dppz2+ (phen = 1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) on DNA binding thermodynamics. The methylated complexes (10-methyl-dppz and 11,12-dimethyl-dppz) have large, concentration-dependent, positive heats of dilution, and a strong endothermic background is also apparent in the ITC-profiles from titration of methylated complexes into poly(dAdT)2, which make direct comparison between complexes difficult. By augmenting a simple cooperative binding model with one equilibrium for complex self-aggregation in solution and one equilibrium for complex aggregation on saturated DNA, it was possible to find an excellent global fit to the experimental data with DNA affinity parameters restricted to be equal for all Δ-enantiomers as well as for all Λ-enantiomers.
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