EVOLUTIONARY MOLECULAR GENETICS OF MITOCHONDRIAL DNA

线粒体 DNA 的进化分子遗传学

• 批准号: 3277755
• 负责人: WESLEY M BROWN
• 金额: $ 13.6万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-02-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3277755
• 关键词: animal population study; autoradiography; developmental genetics; extrachromosomal DNA; gene expression; genome; mitochondrial DNA; molecular cloning; molecular genetics; molecular pathology; nucleic acid sequence; ribosomal RNA

The mitochondrial system of animals is an excellent one in which to study molecular evolution. Its DNA is easily purified, contains genes for 13 proteins, 2 ribosomal RNAs and 22 transfer RNAs, yet is small enough to analyze completely. Mitochondrial DNA (mtDNA) lacks intervening, spacer and repetitive sequences, making its analysis uncomplicated. The same genes are present in all animals, but the gene arrangement can change. MtDNA is inherited maternally and is thus free of complications caused by biparental inheritance. The sequence of vertebrate mtDNA changes rapidly, relative to nuclear DNA, due to both base substitutions and deletion/additions. The most extensive changes occur in one small but interesting region (the D-loop region) which contains the regulatory elements for replication and gene expression. Comparisons in this region will allow us to identify sequences that may be important to these functions. Changes in vertebrate mtDNA can be correlated with time, via the fossil record. Two basic questions regarding the evolution of vertebrate mtDNA will be addressed: (1) What kinds of sequence changes occur and in what proportions, and (2) how can a high rate of sequence change be tolerated in the genome of an organelle whose functions are so vital for the cell? To answer these, mtDNA will be obtained from a series of species whose divergence times are well known. The same mitochondrial genes will be cloned and sequenced from each. The sequences will be compared, and the kinds and relative proportions of the changes determined. Changes will be analyzed with respect to the functions of the genes in which they occur. Useful information about constraints on molecular structure and function and how constraints are affected by genome size should be obtained. Also, two instances of sequence rearrangement in the D-loop will be analyzed in order to gain insight into the mechanistic basis of rearrangements. A long-term study of mitochondrial DNA from other major animal groups will be initiated. The immediate goals of the study are to define the total range of variation present in animal mtDNA and to test the generality of the knowledge that has been obtained from studies of vertebrate mtDNAs. The groups chosen include, respectively, the causative agents of schistosomiasis and their intermediate hosts. Knowledge of the biology of these organisms may ultimately lead to methods of control.

动物的线粒体系统是一个很好的研究对象 分子进化 它的DNA很容易纯化，含有13个基因 蛋白质，2核糖体RNA和22转移RNA，但足够小， 全面分析。 线粒体DNA（mtDNA）缺乏间插间隔区 和重复序列，使其分析不复杂。 相同的 基因存在于所有动物中，但基因排列可以改变。 MtDNA是母系遗传的，因此没有由遗传引起的并发症。 双亲遗传 相对于核DNA，脊椎动物mtDNA的序列变化很快， 由于碱基替换和缺失/添加。 最广泛的 变化发生在一个小但有趣的区域（D环区域）， 含有复制和基因表达的调控元件。 在这一区域的比较将使我们能够识别序列， 对这些功能很重要。 脊椎动物线粒体DNA的变化可以 通过化石记录与时间相关联。 两个基本问题 脊椎动物线粒体DNA的进化将被解决：（1）什么样的 序列变化发生的比例，以及（2）如何可以高速率 序列变化的细胞器的基因组中， 对细胞来说是如此重要吗 为了回答这些问题，线粒体DNA将 从一系列的物种，其分歧时间是众所周知的。 同样的线粒体基因将被克隆和测序。 的 序列将进行比较，和种类和相对比例的 变化决定。 将根据功能分析变更 它们发生的基因。 有关约束的有用信息 分子结构和功能以及基因组如何影响限制 尺寸应该得到。 此外，两个实例的序列重排， 将对D回路进行分析，以便深入了解 重新安排的基础。 对其他主要动物群体的线粒体DNA进行长期研究， 被启动。 这项研究的直接目标是确定 动物mtDNA中存在的变异范围，并测试 从脊椎动物mtDNA研究中获得的知识。 所选的基团分别包括以下病原体： 血吸虫病及其中间宿主。 生物学知识 这些生物体最终可能导致控制方法。