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Silent but not static: accelerated base-pair substitution in silenced chromatin of budding yeasts.

Teytelman L, Eisen MB, Rine J - PLoS Genet. (2008)

Bottom Line: However, we found evidence of an additional factor in this diversification.Likewise, intra-species analysis of polymorphisms also revealed increased SNP frequencies in both intergenic and synonymous coding positions of silenced DNA.This analysis suggested that silenced DNA in Saccharomyces cerevisiae and closely related species had increased single base-pair substitution that was likely due to the effects of the silencing machinery on DNA replication or repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, California, United States of America.

ABSTRACT
Subtelomeric DNA in budding yeasts, like metazoan heterochromatin, is gene poor, repetitive, transiently silenced, and highly dynamic. The rapid evolution of subtelomeric regions is commonly thought to arise from transposon activity and increased recombination between repetitive elements. However, we found evidence of an additional factor in this diversification. We observed a surprising level of nucleotide divergence in transcriptionally silenced regions in inter-species comparisons of Saccharomyces yeasts. Likewise, intra-species analysis of polymorphisms also revealed increased SNP frequencies in both intergenic and synonymous coding positions of silenced DNA. This analysis suggested that silenced DNA in Saccharomyces cerevisiae and closely related species had increased single base-pair substitution that was likely due to the effects of the silencing machinery on DNA replication or repair.

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Lack of conservation in HML and HMR flanking intergenic regions.The results from the BLAST searches with S. cerevisiae HML and HMR and surrounding sequence against corresponding syntenic S. paradoxus contigs are shown with percent identity plotted for 200-bp windows. Genes are annotated on the x-axis. Segments without significant BLAST matches are shaded.
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pgen-1000247-g002: Lack of conservation in HML and HMR flanking intergenic regions.The results from the BLAST searches with S. cerevisiae HML and HMR and surrounding sequence against corresponding syntenic S. paradoxus contigs are shown with percent identity plotted for 200-bp windows. Genes are annotated on the x-axis. Segments without significant BLAST matches are shaded.

Mentions: To identify the E and I silencers in the sensu stricto species, we searched for peaks of conservation in multiple sequence alignments. For both of the S. cerevisiae HML and HMR, we identified contigs in the sequenced sensu stricto species that contained a part of the locus and the adjacent gene. The right side of HMR was misassembled in S. paradoxus with two disjointed contigs with incorrect inverted ends, so we resequenced and assembled the region (GenBank EU597267). HML and HMR were conserved across all five species with clearly conserved orthologs of the neighboring genes (Table S1). However, unlike most intergenic sequences in the genome, the regions around HML and HMR were too diverged to allow multiple alignments. Moreover, local pairwise alignments of these flanking sequences between any of the ten species pairs were also unexpectedly dissimilar. The best pairwise alignments were between the two closest species S. cerevisiae and S. paradoxus, but instead of the genome-wide average of 80% identity for orthologous intergenic regions, the percent identities were: 46% left of HML, 55% right of HML, 52% left of HMR, 45% right of HMR. These alignments were almost as dissimilar as if the sequences were unrelated; 1000 random equal-length sequences with identical base composition that we generated had an averaged local pairwise similarity of 45%. BLAST-based comparisons also did not reveal matches for the sequences between HML or HMR and the nearest flanking genes, ruling out local inversions and rearrangements (Figure 2).


Silent but not static: accelerated base-pair substitution in silenced chromatin of budding yeasts.

Teytelman L, Eisen MB, Rine J - PLoS Genet. (2008)

Lack of conservation in HML and HMR flanking intergenic regions.The results from the BLAST searches with S. cerevisiae HML and HMR and surrounding sequence against corresponding syntenic S. paradoxus contigs are shown with percent identity plotted for 200-bp windows. Genes are annotated on the x-axis. Segments without significant BLAST matches are shaded.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570616&req=5

pgen-1000247-g002: Lack of conservation in HML and HMR flanking intergenic regions.The results from the BLAST searches with S. cerevisiae HML and HMR and surrounding sequence against corresponding syntenic S. paradoxus contigs are shown with percent identity plotted for 200-bp windows. Genes are annotated on the x-axis. Segments without significant BLAST matches are shaded.
Mentions: To identify the E and I silencers in the sensu stricto species, we searched for peaks of conservation in multiple sequence alignments. For both of the S. cerevisiae HML and HMR, we identified contigs in the sequenced sensu stricto species that contained a part of the locus and the adjacent gene. The right side of HMR was misassembled in S. paradoxus with two disjointed contigs with incorrect inverted ends, so we resequenced and assembled the region (GenBank EU597267). HML and HMR were conserved across all five species with clearly conserved orthologs of the neighboring genes (Table S1). However, unlike most intergenic sequences in the genome, the regions around HML and HMR were too diverged to allow multiple alignments. Moreover, local pairwise alignments of these flanking sequences between any of the ten species pairs were also unexpectedly dissimilar. The best pairwise alignments were between the two closest species S. cerevisiae and S. paradoxus, but instead of the genome-wide average of 80% identity for orthologous intergenic regions, the percent identities were: 46% left of HML, 55% right of HML, 52% left of HMR, 45% right of HMR. These alignments were almost as dissimilar as if the sequences were unrelated; 1000 random equal-length sequences with identical base composition that we generated had an averaged local pairwise similarity of 45%. BLAST-based comparisons also did not reveal matches for the sequences between HML or HMR and the nearest flanking genes, ruling out local inversions and rearrangements (Figure 2).

Bottom Line: However, we found evidence of an additional factor in this diversification.Likewise, intra-species analysis of polymorphisms also revealed increased SNP frequencies in both intergenic and synonymous coding positions of silenced DNA.This analysis suggested that silenced DNA in Saccharomyces cerevisiae and closely related species had increased single base-pair substitution that was likely due to the effects of the silencing machinery on DNA replication or repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, California, United States of America.

ABSTRACT
Subtelomeric DNA in budding yeasts, like metazoan heterochromatin, is gene poor, repetitive, transiently silenced, and highly dynamic. The rapid evolution of subtelomeric regions is commonly thought to arise from transposon activity and increased recombination between repetitive elements. However, we found evidence of an additional factor in this diversification. We observed a surprising level of nucleotide divergence in transcriptionally silenced regions in inter-species comparisons of Saccharomyces yeasts. Likewise, intra-species analysis of polymorphisms also revealed increased SNP frequencies in both intergenic and synonymous coding positions of silenced DNA. This analysis suggested that silenced DNA in Saccharomyces cerevisiae and closely related species had increased single base-pair substitution that was likely due to the effects of the silencing machinery on DNA replication or repair.

Show MeSH