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G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae.

Capra JA, Paeschke K, Singh M, Zakian VA - PLoS Comput. Biol. (2010)

Bottom Line: We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures.We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA.The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.

ABSTRACT
G-quadruplex DNA is a four-stranded DNA structure formed by non-Watson-Crick base pairing between stacked sets of four guanines. Many possible functions have been proposed for this structure, but its in vivo role in the cell is still largely unresolved. We carried out a genome-wide survey of the evolutionary conservation of regions with the potential to form G-quadruplex DNA structures (G4 DNA motifs) across seven yeast species. We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures. We characterized the association of conserved and non-conserved G4 DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features and gene classes. Our comprehensive, integrated evolutionary and functional analysis confirmed the previously observed associations of G4 DNA motifs with promoter regions and the rDNA, and it identified several previously unrecognized associations of G4 DNA motifs with genomic features, such as mitotic and meiotic double-strand break sites (DSBs). Conserved G4 DNA motifs maintained strong associations with promoters and the rDNA, but not with DSBs. We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA. The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint.

Show MeSH
The distribution of G4 DNA motifs across the S. cerevisiae nuclear genome.Each small circle represents the location of a G4 DNA motif in a chromosome. Motifs conserved across the sensu stricto species are highlighted in red.
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pcbi-1000861-g004: The distribution of G4 DNA motifs across the S. cerevisiae nuclear genome.Each small circle represents the location of a G4 DNA motif in a chromosome. Motifs conserved across the sensu stricto species are highlighted in red.

Mentions: Disregarding the G-rich telomeres, the distribution of G4 DNA motifs across the 16 yeast nuclear chromosomes was relatively constant (Fig. 4). Chromosome XVI had the lowest density of G4 DNA motifs with 0.034 G4 sites per kb of sequence, while chromosome VI had the highest at 0.067 per kb. G4 DNA motifs were found across the entire length of most chromosomes (Fig. 4). The longest stretch of the genome without a G4 DNA motif was a 180 kb ORF-rich region on the right arm of chromosome IV (1062535–1242537). A region on the right arm of chromosome VI had the highest density of G4 DNA with seven G4 DNA motifs within ∼16 kb (182580–199009). This region contains a variety of functional elements, including an autonomously replicated sequence (ARS), tRNA genes, several ORFs, and a Ty1 retrotransposon.


G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae.

Capra JA, Paeschke K, Singh M, Zakian VA - PLoS Comput. Biol. (2010)

The distribution of G4 DNA motifs across the S. cerevisiae nuclear genome.Each small circle represents the location of a G4 DNA motif in a chromosome. Motifs conserved across the sensu stricto species are highlighted in red.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908698&req=5

pcbi-1000861-g004: The distribution of G4 DNA motifs across the S. cerevisiae nuclear genome.Each small circle represents the location of a G4 DNA motif in a chromosome. Motifs conserved across the sensu stricto species are highlighted in red.
Mentions: Disregarding the G-rich telomeres, the distribution of G4 DNA motifs across the 16 yeast nuclear chromosomes was relatively constant (Fig. 4). Chromosome XVI had the lowest density of G4 DNA motifs with 0.034 G4 sites per kb of sequence, while chromosome VI had the highest at 0.067 per kb. G4 DNA motifs were found across the entire length of most chromosomes (Fig. 4). The longest stretch of the genome without a G4 DNA motif was a 180 kb ORF-rich region on the right arm of chromosome IV (1062535–1242537). A region on the right arm of chromosome VI had the highest density of G4 DNA with seven G4 DNA motifs within ∼16 kb (182580–199009). This region contains a variety of functional elements, including an autonomously replicated sequence (ARS), tRNA genes, several ORFs, and a Ty1 retrotransposon.

Bottom Line: We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures.We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA.The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.

ABSTRACT
G-quadruplex DNA is a four-stranded DNA structure formed by non-Watson-Crick base pairing between stacked sets of four guanines. Many possible functions have been proposed for this structure, but its in vivo role in the cell is still largely unresolved. We carried out a genome-wide survey of the evolutionary conservation of regions with the potential to form G-quadruplex DNA structures (G4 DNA motifs) across seven yeast species. We found that G4 DNA motifs were significantly more conserved than expected by chance, and the nucleotide-level conservation patterns suggested that the motif conservation was the result of the formation of G4 DNA structures. We characterized the association of conserved and non-conserved G4 DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features and gene classes. Our comprehensive, integrated evolutionary and functional analysis confirmed the previously observed associations of G4 DNA motifs with promoter regions and the rDNA, and it identified several previously unrecognized associations of G4 DNA motifs with genomic features, such as mitotic and meiotic double-strand break sites (DSBs). Conserved G4 DNA motifs maintained strong associations with promoters and the rDNA, but not with DSBs. We also performed the first analysis of G4 DNA motifs in the mitochondria, and surprisingly found a tenfold higher concentration of the motifs in the AT-rich yeast mitochondrial DNA than in nuclear DNA. The evolutionary conservation of the G4 DNA motif and its association with specific genome features supports the hypothesis that G4 DNA has in vivo functions that are under evolutionary constraint.

Show MeSH