西亚试剂：Local DNA Topography Correlates with Functional Noncoding R

Local DNA Topography Correlates with Functional Noncoding Regions of the Human Genome

Stephen C. J. Parker 1, Loren Hansen 2, Hatice Ozel Abaan 3, Thomas D. Tullius 4*, Elliott H. Margulies 3*

1 Bioinformatics Program, Boston University, Boston, MA 02215, USA.
2 Bioinformatics Program, Boston University, Boston, MA 02215, USA.; National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD, USA.
3 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
4 Bioinformatics Program, Boston University, Boston, MA 02215, USA.; Department of Chemistry, Boston University, Boston, MA 02215, USA.

The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein binding affinity and. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species using hydroxyl radical cleavage patterns to interrogate the solvent accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained—double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than regions identified solely on the basis of nucleotide sequence. These results support that the molecular shape of DNA is under selection and can identify evolutionary history.

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