Extensive Changes in the Expression of the Opioid Genes between Humans and Chimpanzees

Abstract

The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences (PENK, PNOC, and OPRL1), with two others marginally significant (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes.

Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives

“…Distal TM domains (TMV–VII) and the intracellular C-terminus are encoded by exon 3 [27]. All genes encoding opioid receptors produce multiple mRNA isoforms, what results from alternative splicing, alternative promoters, but also various sites of polyadenylation and inclusions of non-coding sequences [28]. …”

Toward a Deeper Understanding of the Genetics of Bipolar Disorder

“…According to Darwinian Theory, common, positively selected traits provided an evolutionary advantage, but in the case of some traits, left almost all members of a population vulnerable to the disease (Figure 1 ) ( 23 ). Supporting evidence has come from comparisons of the human genome to the genome of the chimpanzee, which revealed evidence for positive selection in the opioid receptor genes ( 24 ) and immune response genes ( 25 , 26 ). These studies provided support for a link between entire genes or even gene families and common human traits, such as creativity and novelty seeking, which might have not only provided an evolutionary advantage but also made all humankind susceptible to addiction and other psychiatric disorders ( 27 ).…”

The genetics of the opioid system and specific drug addictions

“…The ligands' genes all share overall similar structure with a single intron in the coding region. The opioid system is presumed to have been formed by genome duplications early in vertebrate evolution (Cruz-Gordillo et al 2010; Li et al 1996). Each receptor gene also produces multiple mRNA isoforms through the use of alternative splicing, alternative promoters ( OPRM1, OPRK1 ), alternative polyadenylation sites ( OPRK1 ), or inclusion of non-coding exons.…”