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The Molecular Evolution of Nucleosome Positioning Through Sequence-Dependent Deformation of the DNA Polymer
Authors:G A Babbitt  M Y Tolstorukov  Y Kim
Institution:1. School of Biological and Medical Sciences, Rochester Institute of Technology , Rochester , NY;2. Center for Evolutionary Functional Genomics , The Biodesign Institute Arizona State University , Tempe , Arizona;3. Center for Biomedical Informatics , Harvard Medical School , Boston , Massachusetts;4. Department of Medicine , Brigham and Women's Hospital , Boston , Massachusetts;5. Center for Evolutionary Functional Genomics , The Biodesign Institute Arizona State University , Tempe , Arizona;6. School of Life Sciences Arizona State University Tempe , Arizona
Abstract:Abstract

The computational prediction of nucleosome positioning from DNA sequence now allows for in silico investigation of the molecular evolution of biophysical properties of the DNA molecule responsible for primary chromatin organization in the genome. To discern what signal components driving nucleosome positioning in the yeast genome are potentially targeted by natural selection, we compare the performance of various models predictive of nucleosome positioning within the context of a simple statistical test, the repositioned mutation test. We demonstrate that while nucleosome occupancy is driven largely by translational exclusion in response to AT content, there is also a strong signature of evolutionary conservation of regular patterns within nucleosomal DNA sequence related to the structural organization of the nucleosome core (e.g., 10-bp dinucleotide periodicity). We also use computer simulations to investigate hypothetical coding and regulatory constraints on the ability of sequence properties affecting nucleosome formation to adaptively evolve. Our results demonstrate that natural selection may act independently on different DNA sequence properties responsible for local chromatin organization. Furthermore, at least with respect to the deformation energy of the DNA molecule in the nucleosome, the presence of the genetic code has greatly restricted the ability of sequences to evolve the dynamic nucleosome organization typically observed in promoter regions.
Keywords:Evolution  Nucleosome positioning  Chromatin  Histone  Yeast
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