IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Existence, relative abundance, and putative function of guanine quadruplexes in the model species Danio rerio
Autor/es:
MARGARIT, E.; ARMAS, P.; CALCATERRA, N. B.
Lugar:
Rosario
Reunión:
Congreso; 4to. Congreso Argentino de Bioinformática y Biología Computacional (4CAB2C) y 4ta. Conferencia Internacional de la Sociedad Iberoamericana de Bioinformática (SolBio).; 2013
Institución organizadora:
Sociedad Iberoamericana de Bioinformática (SolBio).
Resumen:
Background
Guanine quadruplexes (G4) are
secondary structures of single-stranded DNA or RNA formed by the stacking of
planar layers of four guanines (tetrads) interacting by Hoogsteen hydrogen
bonds. G4 were characterized in several species and related to specific
biological functions, such as gene expression regulation and chromatin
structure modification. Albeit the widespread use of Danio rerio for
the study of vertebrate gene function, genome-wide studies regarding these structures have
not been performed yet.
Methods and Results
In this work, we performed and
exhaustive analysis of zebrafish genomic, gene, and promoter sequences searching
for putative G4 sequences (PQS). Sequences were downloaded from Ensembl [www.ensembl.org] and scanned for PQS formed by the
stacking of two (G4-2) or three (G4-3) guanine tetrads using Quadparser [www.quadruplex.org]. We found 55,109 G4-3s and
17,137,202 G4-2s in the zebrafish genome. Most of the G4-3s (46%) were found within
transcriptional units, contained either in mature mRNAs (5.6%) or intronic
sequences (94.4%). Furthermore, 79 and 702 G4-3s were detected in 5´- and
3´-UTRs, respectively. Scanning of promoter regions revealed the existence of 1,023
G4-3s (1.8%) in 918 genes. Regarding G4-2s, 819,495 (4.8%) were found in 26,426
transcriptional units, mainly in intronic sequences (98.6%). G4 density was
calculated and compared to the whole genome value. As expected, G4 density was
lower than in warm-blood animals, likely due to the lower GC content of
zebrafish genome. G4-2s were enriched in coding sequences and 5´UTRs, while lower
in 3´ UTRs. No significant differences in G4-3s densities were found among either
coding sequences or 3? UTR, while an impoverishment in G4-3s was detected in
5?UTRs. Furthermore, an enrichment of G4-3s was detected in transcription template
DNA strands. Promoters and mRNAs enriched in PQS were classified according Gene
Ontology (GO) terms using Cytoscape [www.cytoscape.org]. mRNAs grouped in development,
differentiation and embryo morphogenesis, while promoters grouped in regulation
of gene expression, embryo development and morphogenesis. Finally, PQS-containing
promoters from zebrafish, mouse and human were compared resulting in a total of
104 conserved genes grouped in development and gene expression regulation GO
terms.
Conclusions
This study presents a first
draft of the distribution and potential function of G4 in zebrafish genome and
establishes a starting point concerning their role in vertebrate development
and evolution. Although not highly represented in zebrafish genome, we
speculate that PQS in developmental genes have been positively selected during
natural evolution.