Inferring natural selection on fine-scale chromatin organization in yeast
Inferring natural selection on fine-scale chromatin organization in yeast
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DOI：
10.1093/molbev/msn127
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发表时间：
2008-08-01
影响因子：
10.7
通讯作者：
Kim, Y.
中科院分区：
文献类型：
--
作者：
Babbitt, G. A.;Kim, Y.
尽管它在复杂表型的进化中具有潜在的作用，但由于预测突变对非编码序列的功能后果的固有困难，对非编码调控序列的负(纯化)和正选择的检测一直难以捉摸。由于调节序列的功能依赖于染色质构型和顺式调节因子结合，因此我们研究了调节区的功能保守应该与DNA序列依赖的弯曲特性的保守有关的想法，这决定了它与核小体的亲和力。核小体序列依赖亲和力的计算预测的最新进展为区分染色质组织的中性和非中性进化提供了机会。在这里，提出了一种统计检验，用于从DNA序列的物种间比较中检测核小体亲和力的进化保守性和/或适应性进化。用最近发表的两种方法计算了同源序列的局部核小体亲和力。对突变位点进行随机化检验，以评价几种近缘酵母之间DNA-核小体亲和力的相似性。对于我们分析的大多数基因，在上游非编码区的几个不同位置检测到局部核小体亲和力的保守性。我们的结果还表明，染色质进化的不同模式在含TATA基因和不含TATA基因的核心启动子上形成了DNA-核小体相互作用，而在后者的核心启动子中，提高的纯化选择保持了对核小体的低亲和力。在整个酵母基因组中，还发现与含有TATA的基因相比，不含TATA的基因的DNA与核小体的相互作用要保守得多。
Despite its potential role in the evolution of complex phenotypes, the detection of negative (purifying) and positive selection on noncoding regulatory sequence has been elusive because of the inherent difficulty in predicting the functional consequences of mutations on noncoding 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 nonneutral 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 2 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 noncoding region. Our results also demonstrate that different patterns of chromatin evolution have shaped DNA-nucleosome interaction 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 with TATA-containing genes.