Feeding and the rhodopsin family g-protein coupled receptors in nematodes and arthropods

Abstract

In vertebrates, receptors of the rhodopsin G-protein coupled superfamily (GPCRs) play an important role in the regulation of feeding and energy homeostasis and are activated by peptide hormones produced in the brain-gut axis. These peptides regulate appetite and energy expenditure by promoting or inhibiting food intake. Sequence and function homologs of human GPCRs involved in feeding exist in the nematode roundworm, Caenorhabditis elegans (C. elegans), and the arthropod fruit fly, Drosophila melanogaster (D. melanogaster), suggesting that the mechanisms that regulate food intake emerged early and have been conserved during metazoan radiation. Nematodes and arthropods are the most diverse and successful animal phyla on Earth. They can survive in a vast diversity of environments and have acquired distinct life styles and feeding strategies. The aim of the present review is to investigate if this diversity has affected the evolution of invertebrate GPCRs. Homologs of the C. elegans and D. melanogaster rhodopsin receptors were characterized in the genome of other nematodes and arthropods and receptor evolution compared. With the exception of bombesin receptors (BBR) that are absent from nematodes, a similar gene complement was found. In arthropods, rhodopsin GPCR evolution is characterized by species-specific gene duplications and deletions and in nematodes by gene expansions in species with a free-living stage and gene deletions in representatives of obligate parasitic taxa. Based upon variation in GPCR gene number and potentially divergent functions within phyla we hypothesize that life style and feeding diversity practiced by nematodes and arthropods was one factor that contributed to rhodopsin GPCR gene evolution. Understanding how the regulation of food intake has evolved in invertebrates will contribute to the development of novel drugs to control nematodes and arthropods and the pests and diseases that use them as vectors.

Keywords: conservation; evolution; feeding; invertebrates; rhodopsin GPCR.

Figure 1

Overview of endocrine factors that regulate feeding behavior in the human brain-gut axis. In humans and other vertebrates, feeding is regulated by signals from the environment (odor and taste), hunger (metabolic signals), and endocrine signals produced by the gut and brain. The orange arrow represents the blood connection between gut and brain and the black arrow the nervous connection via the vagal afferent terminals through which peptides produced by the gut modulate the feeding response in the brain. GAL, NPY, OX, Ghrelin, and MCH are orexigenic peptides and promote appetite and feeding. CCK, MSH, NMU, BB, NK, SP, NPFF are anorexigenic. The role of SST peptides in feeding is unclear. The full peptide names are indicated in Table 1.

Figure 2

Stylized phylogenetic tree showing the relationship between human GRAFS. The number of human representatives identified within each superfamily is indicated within brackets (Fredriksson et al., 2003). Rhodopsin family members (which are represented by the blue branch) are the most numerous and their members are classified into four main sub-branches (α, β, γ, and δ). Human receptors, which are activated by peptides and have a role in feeding regulation, are members of the rhodopsin and secretin families.

Figure 3

Phylogenetic relationship of the Human (Hsa) rhodopsin GPCRs involved in feeding with the nematode C. elegans (Cel) and arthropod D. melanogaster (Dme) sequence homologs. Trees were constructed using the neighbor joining method with 1000 bootstrap replicates (uniform rate among sites, pairwise deletion using the p-distance substitution model) built in the Mega5.1 program. Receptors were classified into six distinct subfamilies: (A) Gastrin-Cholecystokinin receptors; (B) Neurokinin/neuropeptide FF/orexin receptors, (C) Neuropeptide Y receptors, (D) Bombesin receptors, (E) Ghrelin/obstatin and Neuromedin U receptors, and (F) Somatostatin and galanin receptors. Accession numbers are described in Table 3.

Figure 4

Distribution of rhodopsin subfamily members in nematodes and arthropods. The phylogenetic relationship of the species analyzed is represented on the right and their feeding habits are indicated. The black circle indicates a putative gene duplication event in the nematode radiation and the black cross potential gene deletion in the T. spiralis genome. Genes that were identified based upon sequence similarity but that were not considered for phylogenetic analysis are indicated within brackets “()”; ni- GPCR member not identified, and P represent parasitic nematode and arthropod. The evolutionary relationship within nematodes and arthropods was obtained from (Consortium, ; Sommer and Streit, 2011).

Figure 5

Phylogenetic analysis of the nematode rhodopsin GPCRs. (A) Gastrin-cholecystokinin receptors; (B) Neurokinin/neuropeptide FF/orexin receptors, (C) Neuropeptide Y receptors, (D) Ghrelin-Obstatin/neuromedin U receptors, and (E) Somatostatin and galanin receptors. The C.elegans (Cel) receptors are annotated in bold. C. briggsae (Cbr), C. japonica (Cja), P. pacificus (Ppa) H. contortus (Hco) B. malayi (Bma), T. spiralis (Tsp), and M. incognita (Min). Accession numbers of the sequences used are indicated. Trees were constructed using the sequence alignment displayed in Figure S1 Supplementary Material using the methodology described in Figure 3.

Figure 6

Phylogenetic analysis of the arthropod rhodopsin GPCRs. (A) Gastrin-cholecystokinin receptors; (B) Neurokinin/neuropeptide FF/Orexin receptors, (C) Neuropeptide Y receptors, (D) Bombesin receptors, (E) Ghrelin-Obstatin/Neuromedin U receptors, and (F) Somatostatin and galanin receptors. The D. melanogaster (Dme) receptors are annotated in bold. A. gambiae (Aga), A. aegypti (Aae), A. mellifera (Ame), B. mori (Bmo), and I. scapularis (Isc). Accession numbers of the sequences used are indicated. Trees were constructed using the sequence alignment displayed in Figure S2 in Supplementary Material using a similar approach to that described in Figure 3.

Figure 6

Phylogenetic analysis of the arthropod rhodopsin GPCRs. (A) Gastrin-cholecystokinin receptors; (B) Neurokinin/neuropeptide FF/Orexin receptors, (C) Neuropeptide Y receptors, (D) Bombesin receptors, (E) Ghrelin-Obstatin/Neuromedin U receptors, and (F) Somatostatin and galanin receptors. The D. melanogaster (Dme) receptors are annotated in bold. A. gambiae (Aga), A. aegypti (Aae), A. mellifera (Ame), B. mori (Bmo), and I. scapularis (Isc). Accession numbers of the sequences used are indicated. Trees were constructed using the sequence alignment displayed in Figure S2 in Supplementary Material using a similar approach to that described in Figure 3.