Reference: Babbitt GA and Kim Y (2008) Inferring natural selection on fine-scale chromatin organization in yeast. Mol Biol Evol 25(8):1714-27

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Abstract

Despite its potential role in the evolution of complex phenotypes, the detection of negative (purifying) and positive selection on non-coding regulatory sequence has been elusive because of the inherent difficulty in predicting the functional consequences of mutations on non-coding sequence. Because the functioning of regulatory sequence depends upon both chromatin configuration and cis-regulatory factor binding, we investigate the idea that the functional conservation of regulatory regions should be associated with the conservation of sequence-dependent bending properties of DNA that determine its affinity for the nucleosome. Recent advances in the computational prediction of sequence-dependent affinity to nucleosomes provide an opportunity to distinguish between neutral and non-neutral evolution of fine-scale chromatin organization. Here, a statistical test is presented for detecting evolutionary conservation and/or adaptive evolution of nucleosome affinity from interspecies comparisons of DNA sequences. Local nucleosome affinities of homologous sequences were calculated using two recently published methods. A randomization test was applied to sites of mutation to evaluate the similarity of DNA-nucleosome affinity between several closely related species of Saccharomyces yeast. For most of the genes we analyzed, the conservation of local nucleosome affinity was detected at a few distinct locations in the upstream non-coding region. Our results also demonstrate that different patterns of chromatin evolution have shaped DNA-nucleosome interaction in at the core promoters of TATA-containing and TATA-less genes, and that elevated purifying selection has maintained low affinity for nucleosome in the core promoters of the latter group. Across the entire yeast genome, DNA-nucleosome interaction was also discovered to be significantly more conserved in TATA-less genes compared to TATA-containing genes.

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Journal Article
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Babbitt GA, Kim Y
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