DNA SEQUENCE COMPLEXITY AND MUTATIONAL DYNAMICS

DNA 序列复杂性和突变动力学

• 批准号: 3759318
• 负责人: J WOOTTON
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3759318
• 关键词: DNA; gene mutation; nucleic acid sequence; nucleic acid structure; statistics /biometry; thermodynamics; tissue mosaicism

DNA sequences show enourmous statistical heterogeneity in their local compositional characteristics. This project is investigating the possible causes of the mosaicism in sequence complexity, particularly the roles of mutational biases, medium and long range combinatorial constraints, and correlates of specific functional and structural classes of sequence. A. Distributions of local complexity: Using formal definitions of local compositional complexity of DNA subsequences, the robustness of the Salamon/Konopka maximum entropy relationship has been explored: Given a functionally equivalent set of DNA sequences, the distribution of complexity among all subsequences of this set appears to be as random as possible consistent with the mean complexity of these subsequences. It has now been shown that this maximum entropy effect follows as a consequence of the dynamics of almost any mutational mechanism that incorporates a bias toward low-complexity, for example the neighbor- dependent biases in substitution mutations observed in human genomic mutations. B. Feathered structure of medium range complexity distributions: DNA segments of length range 40 to 200 nucleotides have distributions of compositional complexity with a novel regularity of structure ("feathering"). This is a consequence of the mathematical properties of the local compositional complexity measures when applied to relatively long sequences. The pattern observed in genomic sequences but not in random sequences reflects the nonuniform representation of different complexity classes in natural DNA sequences. Significance of project: The project is beginning to provide detailed explanations for some of the puzzling features found from statistical analyses of DNA sequences, including aspects of the so-called "long range correlations" inferred by other research groups from spectral analysis.

DNA序列在其局部区域显示出巨大的统计异质性。 组成特征 该项目正在调查 序列复杂性中镶嵌现象的可能原因，特别是 突变偏倚的作用，中长期组合 约束，以及特定功能和结构类的相关性 顺序。 A.局部复杂性的分布：使用局部复杂性的形式定义 DNA序列的组成复杂性， Salamon/Konopka最大熵关系已经被探索： 功能等同的DNA序列的集合， 这个集合的所有序列之间的复杂性似乎是随机的， 可能与这些序列的平均复杂度一致。 它 现在已经表明，这种最大熵效应如下： 几乎任何突变机制的动力学结果， 结合了对低复杂度的偏好，例如邻居- 在人类基因组中观察到的替代突变的依赖性偏倚 突变。 B。中程复杂性分布的羽状结构：DNA 长度范围为40至200个核苷酸的片段具有以下分布： 具有新颖的结构规则性的成分复杂性 （“羽化”）。 这是一个数学性质的结果， 局部成分复杂性测量当应用于相对 长序列 在基因组序列中观察到的模式， 随机序列反映了不同的 自然DNA序列的复杂性。项目意义： 项目开始提供详细的解释， 从DNA序列的统计分析中发现的令人困惑的特征， 包括所谓的“长距离相关性”的方面， 其他研究小组从光谱分析。