Limits...
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

Related in: MedlinePlus

The distribution of G4 DNA motifs across the S. cerevisiae mitochondrial DNA.The horizontal black line represents the 75kb mtDNA genome. The rectangles above mark the location of tRNA genes (green), rRNA genes (red), and ORFs (blue). ORFs that encode multiple genes (like COX1, subunit I of cytochrome c oxidase) are drawn as a single rectangle. The vertical black lines below indicate the location of the 32 G4 DNA motifs across the mtDNA. The width of these lines reflects the actual length of the G4 DNA motif. (Note that several motifs are so close that they overlap in the figure.) All motifs are drawn below the mtDNA sequence regardless of the strand on which they occur. The distribution of mitochondiral G4 DNA motifs is biased against overlapping these genomic features; only two of the 32 motifs overlap a tRNA, rRNA, or ORF (q<0.001).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2908698&req=5

pcbi-1000861-g005: The distribution of G4 DNA motifs across the S. cerevisiae mitochondrial DNA.The horizontal black line represents the 75kb mtDNA genome. The rectangles above mark the location of tRNA genes (green), rRNA genes (red), and ORFs (blue). ORFs that encode multiple genes (like COX1, subunit I of cytochrome c oxidase) are drawn as a single rectangle. The vertical black lines below indicate the location of the 32 G4 DNA motifs across the mtDNA. The width of these lines reflects the actual length of the G4 DNA motif. (Note that several motifs are so close that they overlap in the figure.) All motifs are drawn below the mtDNA sequence regardless of the strand on which they occur. The distribution of mitochondiral G4 DNA motifs is biased against overlapping these genomic features; only two of the 32 motifs overlap a tRNA, rRNA, or ORF (q<0.001).

Mentions: A previous analysis of the G4 DNA motifs in the yeast genome did not consider the mtDNA [10]. We found that mtDNA had an order of magnitude more G4 DNA motifs per kb (0.373) than any of the nuclear chromosomes (0.034–0.067). This high density is surprising because the yeast mtDNA is far more AT-rich than the nuclear genome (83% AT in mtDNA compared to 62% AT genome-wide). The distribution of the G4 DNA motifs across the mtDNA was biased towards regions that do not encode ORFs, rRNA, or tRNA genes (Fig. 5). Only two of the 32 mitochondrial G4 DNA motifs overlapped an ORF, and none of the motifs overlapped tRNA or rRNA genes (q<0.001 for this amount of overlap with mitochondrial features). Due to the lack of sequence information for the mtDNA in other fungi, we were not able to analyze the evolutionary conservation of the mitochondrial G4 DNA motifs.


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 mitochondrial DNA.The horizontal black line represents the 75kb mtDNA genome. The rectangles above mark the location of tRNA genes (green), rRNA genes (red), and ORFs (blue). ORFs that encode multiple genes (like COX1, subunit I of cytochrome c oxidase) are drawn as a single rectangle. The vertical black lines below indicate the location of the 32 G4 DNA motifs across the mtDNA. The width of these lines reflects the actual length of the G4 DNA motif. (Note that several motifs are so close that they overlap in the figure.) All motifs are drawn below the mtDNA sequence regardless of the strand on which they occur. The distribution of mitochondiral G4 DNA motifs is biased against overlapping these genomic features; only two of the 32 motifs overlap a tRNA, rRNA, or ORF (q<0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000861-g005: The distribution of G4 DNA motifs across the S. cerevisiae mitochondrial DNA.The horizontal black line represents the 75kb mtDNA genome. The rectangles above mark the location of tRNA genes (green), rRNA genes (red), and ORFs (blue). ORFs that encode multiple genes (like COX1, subunit I of cytochrome c oxidase) are drawn as a single rectangle. The vertical black lines below indicate the location of the 32 G4 DNA motifs across the mtDNA. The width of these lines reflects the actual length of the G4 DNA motif. (Note that several motifs are so close that they overlap in the figure.) All motifs are drawn below the mtDNA sequence regardless of the strand on which they occur. The distribution of mitochondiral G4 DNA motifs is biased against overlapping these genomic features; only two of the 32 motifs overlap a tRNA, rRNA, or ORF (q<0.001).
Mentions: A previous analysis of the G4 DNA motifs in the yeast genome did not consider the mtDNA [10]. We found that mtDNA had an order of magnitude more G4 DNA motifs per kb (0.373) than any of the nuclear chromosomes (0.034–0.067). This high density is surprising because the yeast mtDNA is far more AT-rich than the nuclear genome (83% AT in mtDNA compared to 62% AT genome-wide). The distribution of the G4 DNA motifs across the mtDNA was biased towards regions that do not encode ORFs, rRNA, or tRNA genes (Fig. 5). Only two of the 32 mitochondrial G4 DNA motifs overlapped an ORF, and none of the motifs overlapped tRNA or rRNA genes (q<0.001 for this amount of overlap with mitochondrial features). Due to the lack of sequence information for the mtDNA in other fungi, we were not able to analyze the evolutionary conservation of the mitochondrial G4 DNA motifs.

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
Related in: MedlinePlus