Evolution and Function of Primate Cytochrome c oxidase Gene

灵长类细胞色素c氧化酶基因的进化与功能

• 批准号: 9816923
• 负责人: Lawrence Grossman
• 金额: $ 33.5万
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9816923&HistoricalAwards=false
• 关键词: Evolution; Function; Primate; Cytochrome; oxidase

Cytochrome c oxidase (COX) comprises 13 subunits in mammals; three encoded in mitocondrial (mt) DNA and ten in nuclear DNA. Analysis of the evolution pattern of individual subunits can suggest tests of function and can serve as a model for the evolution of a multisubunit complex. In humans, the COX complex is unique among mammals in lacking the heart isoform of subunit VIII, which was apparently silenced sometime in primate evolution. The lineage in which it was lost will be identified, the promoter regions of COX8 heart and liver isoforms from closely related lineages will be isolated and characterized, and reporter constructs will be used to evaluate their tissue-specificity and activity in differentiated and undifferentiated myoblasts. COX7A isoform genes have mitochondrial targeting presequences which previous results suggest are involved in tissue-specific isoform function. This was unexpected because the presequences are removed during mitochondrial import and are thought not to participate in COX function. To investigate the potential for differential presequence function, the intracellular location of each of the two isoform proteins will be examined in cells that express both. Finally, the nucleotide substitution rates of three selected nuclear subunits will be determined.COX provides a model system to test whether evolution of nuclear genes is parallel to that of mitochondrial genes with which they come in structural contact or functionally interact.

细胞色素c氧化酶（考克斯）在哺乳动物中由13个亚基组成，其中3个编码于线粒体DNA，10个编码于核DNA。对单个亚基的进化模式的分析可以建议功能测试，并可以作为多亚基复合物进化的模型。 在人类中，考克斯复合体在哺乳动物中是独一无二的，因为它缺乏亚单位VIII的心脏同种型，而亚单位VIII在灵长类进化的某个时候显然是沉默的。将鉴定其丢失的谱系，将分离和表征来自密切相关谱系的COX 8心脏和肝脏亚型的启动子区域，并使用报告构建体来评估其在分化和未分化成肌细胞中的组织特异性和活性。COX7A亚型基因具有线粒体靶向前序列，先前的结果表明其参与组织特异性亚型功能。这是出乎意料的，因为前序列在线粒体输入过程中被去除，并且被认为不参与考克斯功能。为了研究差异前序列功能的可能性，将在表达这两种蛋白的细胞中检查两种亚型蛋白中的每一种的细胞内位置。考克斯提供了一个模型系统来测试核基因的进化是否与线粒体基因的进化平行，它们与线粒体基因在结构上接触或功能上相互作用。