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RNases for understanding the origin of new gene function

用于了解新基因功能起源的 RNA 酶

基本信息

批准号：
7155520
负责人：
JIANZHI ZHANG
金额：
$ 15.96万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-01-01 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7155520
关键词：
Address Affect Alleles Amino Acid Substitution Amino Acids Anti-Bacterial Agents Antiviral Agents Arginine Bacteria Biochemical Biodiversity Biological Assay Biological Models Blood Vessels Bos taurus Cattle Cleaved cell Cysteine Data Digestion Disulfides Endoribonucleases Enzymatic Biochemistry Enzymes Eosinophil cationic protein Eosinophil-Derived Neurotoxin Event Evolution Family Gene Duplication Genes Genetic Genetic Variation Growth Health Host Defense Human Immunity In Vitro Infection Laboratories Malignant Neoplasms Mammals Modeling Molecular Numbers Object Attachment Organism Pancreatic ribonuclease Pattern Personal Satisfaction Physiological Processes Play Pongidae Population Primates Process Property Proteins RNA RNA Viruses RNase 2 RNase-5 Ribonucleases Rodent Role Science Site Site-Directed Mutagenesis Testing Vertebrates Virus angiogenesis angiogenin bactericide disulfide bond duplicate genes experience gene function innovation member mutant novel research study ribonuclease k6 theories tumor growth

项目摘要

The long-term objective of my laboratory is to understand how new genes with novel functions originate and how these molecular innovations contribute to the survival, adaptation, and evolution of organisms. Although it is well known that gone duplication plays an important role in the evolution of novel gone functions, the evolutionary forces and molecular mechanisms underlying functional changes of duplicated genes remain poorly understood. Here the ribonuclease (RNase) A gene superfamily of mammals is used as a model system to address the above questions, because (1) the superfamily includes many recently duplicated genes with distinct functions, (2) these functions can be assayed relatively easily in vitro, with the feasibility of analyzing mutant proteins generated by site-directed mutagenesis, (3) members of the superfamily are involved in immunity and cancer and are related to human health, and (4) substantial biochemical, structural, and functional information is available on the superfamily. Eight members of the superfamily are known in humans, and they are pancreatic RNase (or RNase 1), eosinophil-derived neurotoxin (EDN or RNase 2), eosinophil cationic protein (ECP or RNase 3), RNase 4, angiogenin (or RNase 5), RNase k6 (or RNase 6), RNase 7, and RNase 8. As enzymes, all of them can cleave phospodiester bonds in RNA. But they have also evolved other functions and are involved in various physiological processes including digestion of dietary RNAs, angiogenesis, and host defenses. Our specific aims are (1) to test two competing theories on the origin of new gene function by functional characterization of the reconstructed common ancestral gone of the duplicated EDN and ECP genes of higher primates, which have antiviral and antibacterial activities, respectively; (2) to identify amino acid substitutions responsible for the antibacterial function of ECP; (3) to identify amino acid substitutions that led to the potent ribonuclease activity and antiviral activity in EDN; (3) to investigate the recent emergence of an bactericidal alleleic form of the RNase 7 gene in humans and to test its potential role in human health and evolution; (5) to study the evolution of disulfide-bridging in RNase 8 among hominoids and the functional consequences cause by changes in disulfide bonds; and (6) to study the cause of the rapid evolution of primate angiogenin and to identify key amino acid residues necessary for the angiogentic activity in angiogenin.

我实验室的长期目标是了解具有新功能的新基因是如何产生的