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Studying the evolution of gene regulation at the protein level in primates

研究灵长类动物蛋白质水平基因调控的进化

基本信息

批准号：
7545152
负责人：
George Herbert Perry
金额：
$ 4.48万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-11 至 2011-08-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7545152
关键词：
Accounting Antibodies Area Biological Process Categories Complex Data Analyses Disease susceptibility Drug Metabolic Detoxication Epitopes Evolution Gene Expression Gene Expression Regulation Genes Genomics Goals Heart Human Immune Individual Kidney Label Linear Models Liver Liver Extract Lung Macaca Macaca mulatta Measurement Mediating Messenger RNA MicroRNAs Microarray Analysis Modeling Modification Molecular Profiling Natural Selections Numbers Pan Genus Pan troglodytes Pattern Play Primates Protein Hybridization Proteins Proxy Recording of previous events Regulatory Pathway Reporting Research Design Role Sampling Scanning Selection Criteria Spottings Technology Testis Thinking Time Tissues Transcript Variant Work base defense response expectation human disease human tissue insight interest nonhuman primate novel numb protein protein expression protein function species difference trait

项目摘要

DESCRIPTION (provided by applicant): The goal of this study is to identify proteins whose expression levels have evolved under natural selection in humans and non-human primates. Variation in gene regulation, both at the transcriptional and translational levels, is thought to be involved in human phenotypic diversity including disease susceptibility, and is hypothesized to have played an important role in human evolution. Although most previous work in this area has focused on mRNA levels, proteins are usually more directly involved in biological processes. Moreover, complex translational regulatory mechanisms can influence protein levels independent of transcript abundance. Therefore, the characterization of variation in protein levels in humans and non-human primates is expected to provide considerable insight into the genomic mechanisms that may have played important roles in our evolutionary history. In this study, I will (i) develop an antibody microarray platform for highthroughput measurements of steady-state protein expression levels in multiple primate species, (ii) use this platform for comparisons of human, chimpanzee (Pan troglodytes), and rhesus macaque (Macaca mulatta) liver, kidney, heart, lung and testis tissues, and (iii) examine ratios of intra- and inter-specific variation to identify proteins whose expression levels have evolved under stabilizing selection across primates or directional selection in the human lineage. These proteins may be involved in human diseases, for example when expression levels are perturbed. Furthermore, proteins with adaptive changes in steady-state expression levels may have been important in the evolution of human-specific traits, which will be explored using analyses of protein functions and patterns of expression and natural selection by tissue. Variation in protein expression levels is thought to be involved in human phenotypic diversity including disease susceptibility, and may have played an important role in human evolution. This study will use highthroughput technologies to compare protein expression levels across five different tissues from humans, chimpanzees, and rhesus macaques, to identify proteins with expression levels that (i) are highly similar among the three primate species, and (ii) have significantly increased or decreased along the human lineage. Such proteins may be involved in human diseases, for example when expression levels are perturbed, and proteins with significant human lineage changes in expression levels may have been important in the evolution of physical traits that are unique to our species.

描述（由申请人提供）：