Deciphering the Evolution of the Opioid/Orphanin Gene Family

University Of Denver, Denver CO

Investigators

Abstract

A striking feature of chemical communication systems in the brains of jawed vertebrates (gnathostomes) is the apparent duplication of genes that produce useful neuropeptide compounds. For example, in mammals there are four neuropeptide precursors (proenkephalin, prodynorphin, proopiomelanocortin, and proorphanin) that produce opiate-like peptides (opioids) or nociceptic-like peptides (orphanins). These four precursors are members of a gene family, the opioid/orphanin family, and the apparent redundancy of genes in this family in fact reflects the evolutionary history of the vertebrates. Gene duplication events at discrete points in vertebrate evolution have allowed for the layering of neuropeptide networks over time, and have led to a diversification in function of these peptide products, including roles in analgesia, nociception, motor control, and feeding. This project combines molecular biology procedures with a comparative approach to define trends in the evolutionary radiation of the orphanin/opioid gene family in gnathostomes. The cloning and sequencing of cDNAs, coupled with the measurement of gene expression by real-time PCR, will generate a database of sequences for each gene in the family that will be used to perform cladistic analyses and to identify novel opioid sequences. By examining selected vertebrate lineages where the evolution of this gene family has been slower than in mammals or teleost fish, it is possible to make inferences about the origin and transitions in the sequential evolution of this gene family. These data will test the 'proenkephalin hypothesis' that the ancestral gene in the opioid/orphanin gene family was a gene that coded for the enkephalin-like product. Results will provide a new level of understanding of the evolutionary mechanisms underlying the functional diversity in this important family of neuropeptides. The impact of this project will extend beyond neuroendocrinology to molecular neurobiology in general, and to evolutionary biology with respect to the trends that promote species diversity. Multi-disciplinary undergraduate and graduate training also is an important component of this project.