|JIANG, HONGBO - Kansas State University|
|WEI, ZHAOJUN - Kansas State University|
|ADAMS, MICHAEL - University Of California|
|PARK, YOONSEONG - Kansas State University|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2014
Publication Date: 10/28/2014
Citation: Jiang, H., Wei, Z., Nachman, R.J., Adams, M., Park, Y. 2014. Functional phylogenetics reveals contributions of pleiotropic peptide action to ligand-receptor coevolution. Scientific Reports. 4:6800.
Interpretive Summary: Insect pests have developed resistance to several conventional pesticides, and new approaches are needed for pest management. Although neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions, the neuropeptides hold little promise as pest control agents because they can be degraded in the target pest. New, selective control agents may be developed by designing mimics of these neuropeptides that resist degradation and either inhibit or over-stimulate critical neuropeptide-regulated life functions. In this study, we explore the relatedness of the ‘active sites’ from a stored grain pest, the red flour beetle, that are associated with five different neuropeptides that separately regulate the critical life functions of water balance, the protective state of diapause (‘hibernation’), reproduction, development, and digestion. All of the five are related, although some have closer associations than others. Therefore, neuropeptides from each group showed a propensity to cross-activate the active sites of others to different degrees. The work can lead to the identification of specific chemical structures necessary to either turn on all active sites, or to selectively turn on one or a few to the exclusion of others. This discovery, and the new information gained from it, will aid in the design of neuropeptide-like compounds capable of selectively disrupting critical life functions in pest insects while sparing insects beneficial to man and agriculture. This may eventually lead to development of practical neuropeptide-like substances that can effectively control pest insects in an environmentally friendly fashion.
Technical Abstract: The evolution of peptidergic signaling has been accompanied by a significant degree of ligand-receptor coevolution. Closely related clusters of peptide signaling molecules are observed to activate related groups of receptors, implying that genes encoding these ligands may orchestrate an array of functions, a phenomenon known as pleiotropy. Here we examine whether pleiotropic actions of peptide genes might influence ligand-receptor coevolution. Four test groups of neuropeptides characterized by conserved C-terminal amino acid sequence motifs and their cognate receptors were examined in the red flour beetle (Tribolium castaneum): 1) cardioacceleratory peptide 2b (CAPA); CAPAr, 2) pyrokinin/diapause hormone (PK1/DH); PKr-A, -B, 3) pyrokinin/pheromone biosynthesis activating hormone (PK2/PBAN); PKr-C, and 4) ecdysis triggering hormone (ETH); ETHr-b. Ligand-receptor specificities were established through heterologous expression of receptors in cell-based assays for 9 endogenous ligands. Based on ligand-receptor specificity analysis, we found positive pleiotropism exhibited by ETH on ETHR-b and CAPAr, whereas PK1/DH and CAPA are more highly selective for their respective authentic receptors than would be predicted by phylogenetic analysis. Disparities between evolutionary trees deduced from receptor sequences vs. functional ligand-receptor specificities lead to the conclusion that pleiotropy exhibited by peptide genes influences ligand-receptor coevolution.