ORIGINS OF THE CG-RICH ISOCHORES OF THE HUMAN GENOME

人类基因组富含 CG 的等位基因的起源

• 批准号: 3305083
• 负责人: WEN-HSIUNG LI
• 金额: $ 12万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3305083
• 关键词: DNA replication origin; biochemical evolution; gene mutation; genes; genetic library; genetic markers; genome; human genetic material tag; molecular cloning; nucleic acid sequence

Our long-term goal is to know the factors that determine the compositional patterns in various regions of the human genome by a combination of molecular and statistical methods. In particular, we want to know: (1) Do the GC-rich isochores (compositionally homogeneous DNA segments) have any functional significance? These isochores represent about one-third of the genome of humans and other warm-blooded vertebrates, but are nearly absent in cold-blooded vertebrates. Usually they are located in Giemsa light (R) bands of metaphase chromosomes and replicate early in the cell cycle, whereas most GC-poor isochores are located in Giemsa dark (C) bands and replicate late in the cell cycle. The origin of the GC-rich isochores is mysterious. One hypothesis is that the GC-rich isochores arose because of functional (selective) advantages whereas another hypothesis postulates that they arose from different mutational biases in different DNA regions in the replication of germline DNA. (2) Is "GC-richness" a good gene marker? And is the GC level at the third position of codons generally higher than the level in noncoding regions, so that this feature is useful for identifying coding regions? (3) What is the role of CpG islands in gene regulation? (4) Does the rate of mutation in a DNA region depend on its GC content? (5) Are the selective constraints on the usage of synonymous codons in vertebrate genes strong enough to affect the GC level and the rate of substitution at degenerate sited of codons? To investigate the above questions we propose to (a) clone and sequence several high, intermediate and low GC regions from Homo sapiens and Galago crassicaudatus (a primate). We will use the data to be obtained and data from other laboratories to study: (b) Do most GC-rich regions occur in or near coding regions? (c) Rates of nucleotide substitution in regions with different GC levels, (d) Evolutionary change of GC content and CpG dinucleotides in vertebrate and invertebrate genomes, (e) Variation of GC content among the various regions of a gene, and (f) Rates of silent substitution in coding and noncoding regions. A comparison of these rates can reveal the strength of selective constraints on the usage of synonymous codons.

我们的长期目标是了解决定组成的因素 人类基因组各个区域的模式通过结合 分子和统计方法。 特别是我们想知道： （1）做富含GC的等化位置（组成均匀的DNA 细分）具有任何功能意义？这些等距代表 人类和其他温血脊椎动物的基因组的三分之一，但 冷血脊椎动物几乎不存在。 通常他们位于 中期染色体的Giemsa Light（R）带并在早期复制 细胞周期，而大多数GC贫乏的等距位于Giemsa Dark（C） 频带并在细胞周期后期复制。 GC富裕的​​起源 等距是神秘的。 一个假设是富含GC的等距 由于功能（选择性）优势而出现 假设假设它们来自不同的突变偏见 种系DNA复制中的不同DNA区域。 （2）“ gc-richness”是一个好的基因标记吗？并且是GC级别 密码子的第三位置通常高于非编码的水平 区域，以便此功能对于识别编码区域有用吗？ （3）CpG岛在基因调节中的作用是什么？ （4）DNA区域中突变的速率取决于其GC 内容？ （5）是对同义密码子使用的选择性约束 脊椎动物基因足以影响GC水平和速率 换人的密码子替换？ 为了调查上述问题，我们建议（a）克隆和 序列来自Homo Sapiens的几个高，中间和低的GC区域 和Galago Crassicaudatus（灵长类动物）。 我们将使用要获得的数据 和其他实验室的数据进行研究：（b）大多数富含GC的区域 发生在编码区域中还是附近？ （c）核苷酸取代的速率 GC含量不同的区域，（d）GC含量的进化变化和 脊椎动物和无脊椎动物基因组中的CpG二核苷酸，（e）变化 基因的各个区域之间的GC含量，（f）无声的速率 替换编码和非编码区域。 这些费率的比较 可以揭示选择性约束的强度对同义词的使用 密码子。