GENETICS AND EVOLUTION OF THE CARBONIC ANHYDRASE

利用三种碳酸酐酶（CA）同工酶（CA I、CA II、CA III）作为一种酶， 模型多位点酶系统，我们建议研究的分子进化 来自共同祖先基因的同工酶，以及 调节它们在人类和其他脊椎动物细胞中的表达。 特别是， 我们的研究方向是：1）人类的进化起源 CA同工酶，2）突变和进化变化对 不同CA同工酶的调节和功能，以及3）组织 和哺乳动物细胞中CA基因的结构。 我们计划继续研究几种CA的氨基酸序列 从多种哺乳动物和非哺乳动物来源纯化的同工酶及其用途 这一信息，以研究CA同工酶的进化速度比较 因为它们起源于一个共同祖先基因的基因复制。 我们将 还试图从化学上表征最近发现的几种 人红细胞CA I和CA II。 由于相当不寻常（相比之下， CA Ⅰ和CA Ⅱ同工酶的动态和分布特征 发现了哺乳动物肌肉和肝脏的CA III同工酶，我们希望扩大我们的研究范围。 活性部位特有残基修饰的初步研究 从人以及选定的非哺乳动物中纯化的CA III分子 源 通过这样的研究，我们希望能对“真”有更多了解 CA III同工酶的生理作用。

Utilizing the three carbonic anhydrase (CA) isozymes (CA I, CA II, CA III) as a model multilocus enzyme system, we propose to study the molecular evolution of isozymes derived from a common ancestral gene, as well as the mechanisms which regulate their expression in human and other vertebrate cells. In particular, we are directing our research toward: 1) the evolutionary origins of the human CA isozymes, 2) the effect of mutations and evolutionary change on the regulation and function of the different CA isozymes, and 3) the organization and structure of CA genes in mammalian cells. We plan to continue our studies on the amino acid sequences of several CA isozymes purified from a variety of mammalian and non-mammalian sources, and use this information to study the comparative rates of evolution of the CA isozymes since their origin by gene duplication from a common ancestral gene. We will also attempt to chemically characterize several recently discovered variants of human red cell CA I and CA II. Because of the rather unusual (compared to the CA I and II isozymes) kinetic and distributional characteristics of the recently discovered CA III isozymes of mammalian muscle and liver, we wish to expand our preliminary studies on the modificatton of residues unique to the active site of the CA III molecules purified from human as well as selected non-mammalian sources. Through such studies, we hope to understand more about the "true" physiological roles of the CA III isozymes.