engleski

SitaRam: a computational approach for multiperspective visualization of higher-order and progressive patterns in highly repetitive regions of DNA

Background and Purpose: Highly repetitive DNA sequences localized in centromeric and telomeric regions of chromosomes have essential roles in cell division and aging, respectively. (Peri)centromeric and (sub)telomeric repetitive DNA sequences are poorly understood because they exhibit extreme complexity and polymorphism of sequence and organization at all levels and because they are not yet fully assembled. The objective of this work was to develop the model for computational visualization of universal features as well as the variability that characterize the architecture of these DNA regions directly from their primary sequence using a repeat-finding strategy combined with color-coding of sequence- relatedness. The main purpose was to provide detailed maps that would help in understanding the relationship between the primary sequence, organization, evolutionary history and function of repetitive DNA sequences in eukaryotic genomes. Materials and Methods: The proposed approach, named SitaRam, is based on application of BLAST (blastn and bl2seq), MapDraw, multicolor DotPlot, Clustal and Sfor methods. It was developed on AC017075 and AC019063 BAC clone sequences that encompass the centromere gap at the human chromosome 7. Results: SitaRam approach was found to be equally suitable for the visual analysis of »new« and »old« alpha-satellite DNA arrays. Provided here are graphic presentations of the discontinuous progressive pattern at the border of the centromeric D7Z1 array and presentations of the entire multimerically arranged D7Z2 array together with its monomerically arranged surrounding. Multicolor, multiscale and multiregister visualization of tandem repeat variants within satellite arrays in their sequential order revealed diverse hallmarks of unequal crossover as the process generating these arrays. By DotPlot merging, a difference in the frequency and distribution pattern of CENP-B boxes is revealed between alpha-satellite domains characterized by higher-order, progressive and irregular monomeric organization. Conclusions: The proposed representations are characterized by small space requirements and enable simultaneous visualization of diverse types of satellite and interspersed DNA sequences, their inversions, insertions, deletions and potential protein- binding sites. According to the appearance of repetitive patterns, satellite DNA arrays can be visually classified in respect to their evolutionary age, chromosomal location and function. Among the potentials of this model are the comparative analysis of repetitive DNA sequences originating from different eukaryotes and from diverse parts of their chromosomes, the evaluation of individual polymorphism, the detection of as yet unidentified sequences, information compression and simplification of education on repetitive DNAs.

pattern visualization ; high-resolution DNA mapping ; evolution ; alpha-satellite DNA ; interspersed DNA ; CENP-B boxes ; higher-order organization ; monomeric organization ; gradient of divergence ; unequal crossover

Errata corrige, Periodicum Biologorum. 108, 1 ; 109.