LONG-RANGE CORRELATIONS IN DNA SEQUENCES

最近，尺度不变的长程关联的存在 跨越数千个碱基对--有时跨越 整个染色体-已经在DNA序列中被证明包含 非编码材料。虽然蛋白质编码的机制很好 了解，对非编码部分的作用知之甚少 基因组(内含子和基因组间序列)包含超过2/3的 某些真核生物的整个基因组长度。的研究。 长程相关性可能会提供一种更好地区分 基因组序列的编码区和非编码区。它还可以回答一个 关于组织、进化、空间的问题数量 非编码基因组材料的结构和功能。 我们正在请求NIH的支持，以与 以下是具体目标： 1)系统地测试假设(基于我们的初步 观察)信使RNA和外显子序列通常只有 短程相关性，而内含子和基因组间序列 标度不变的长程关联；此外，还测试了 通过我们设计的新的统计方法进行的观察 特别适用于非静态系统，如DNA序列。 2)定量描述DNA中已知的动态现象的作用 进化--例如在内部和之间复制和洗牌片段 染色体、重复元件的插入和内含子的缺失； 开发DNA基因组组织的进化模型并对其进行测试 大量的DNA序列，并检验长距离的假设 相关性与地球表面的三维空间结构有关 染色体中的DNA分子。 3)开发了一种新的统计编码序列查找(CSF)算法，该算法 自动识别编码区，基于我们发现的长- 范围相关性存在于非编码区，在编码中不存在 DNA序列的区域。 这些目标与检测编码的实际需要直接相关 DNA序列中的区域以及理解的长期目标 非编码DNA序列在全球基因组结构中的作用， 组织和进化。

Recently the existence of scale-invariant long-range correlations extending across thousands of base pairs-and sometimes over the length of the entire chromosome-has been demonstrated in DNA sequences that contain non-coding material. While the mechanism for protein coding is well understood, little is known about the role of noncoding parts of the genome (introns and intergenomic sequences) that comprise more than 2/3 of the entire genome length in some eukaryotic species. The study of long.range correlations may provide a tool for better distinguishing coding and non-coding regions of genomic sequences. It may also answer a number of questions regarding the organization, evolution, spatial structure, and function of the noncoding genomic material. We are requesting NIH support to carry out investigations with the following specific aims: 1) Systematically test the hypothesis (based upon our preliminary observations) that messenger RNA and exon sequences usually have only short range correlations while introns and intergenomic sequences have scale-invariant long-range correlations; also, test the universality of this observation by new statistical methods that we have designed specifically for non.stationary systems such as DNA sequences. 2) Quantitatively characterize the role of known dynamic phenomena in DNA evolution-such as duplication and shuffling fragments within and between chromosomes, insertion of repetitive elements and intron deletion; also, develop an evolutionary model of DNA genome organization and test it on large number of DNA sequences, and test the hypothesis that long-range correlations are related to the three-dimensional spatial structure of the DNA molecule in the chromosome. 3) Develop a new statistical "Coding Sequence Finder" (CSF) algorithm that automatically identifies coding regions, based upon our finding that long- range correlations exist in non-coding regions and do not exist in coding regions of DNA sequences. These aims are directly related to the practical need of detecting coding regions in DNA sequences as well as the long term goal of understanding the role of non-coding DNA sequences in global genomic structure, organization, and evolution.