Abstract
In the age of genomics, DNA is depicted as a string of letters. While this is a useful device for representing the information in a genome, the molecular nature of DNA is obscured. Proteins cannot actually “read” DNA letters – they discriminate between DNA binding sites via molecular recognition, which is sensitive to DNA structure. Since shape is essential to DNA’s biological function, we hypothesized that natural selection can act to preserve DNA shape without maintaining the exact sequence of nucleotides. To test this hypothesis, we developed a DNA structure database, ORChID, and used it to map structural variation throughout the human genome. We then devised a computational algorithm, Chai, to detect evolutionary constraint on DNA shape. We found that Chai regions correlate better with experimental functional elements than do genomic regions that are sequence-constrained. Our results support the hypothesis that DNA shape can be a substrate for natural selection.
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Acknowledgments
This work was funded by a grant to T.D.T. from the National Human Genome Research Institute (NHGRI) of the NIH (R01 HG003541). E.H.M. was supported by the Intramural Research Program of the NHGRI, NIH. S.C.J.P. was the recipient of a National Academies Ford Foundation Dissertation Fellowship.
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Tullius, T.D., Parker, S.C.J., Margulies, E.H. (2011). Evolutionary Constraint on DNA Shape in the Human Genome. In: Pontarotti, P. (eds) Evolutionary Biology – Concepts, Biodiversity, Macroevolution and Genome Evolution. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20763-1_14
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DOI: https://doi.org/10.1007/978-3-642-20763-1_14
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