title: Unravelling the Evolution of the Allatostatin-Type A, KISS and Galanin Peptide-Receptor Gene Families in Bilaterians: Insights from Anopheles Mosquitoes.
abstract: Allatostatin type A receptors (AST-ARs) are a group of G-protein coupled receptors activated by members of the FGL-amide (AST-A) peptide family that inhibit food intake and development in arthropods. Despite their physiological importance the evolution of the AST-A system is poorly described and relatively few receptors have been isolated and functionally characterised in insects. The present study provides a comprehensive analysis of the origin and comparative evolution of the AST-A system. To determine how evolution and feeding modified the function of AST-AR the duplicate receptors in Anopheles mosquitoes, were characterised. Phylogeny and gene synteny suggested that invertebrate AST-A receptors and peptide genes shared a common evolutionary origin with KISS/GAL receptors and ligands. AST-ARs and KISSR emerged from a common gene ancestor after the divergence of GALRs in the bilaterian genome. In arthropods, the AST-A system evolved through lineage-specific events and the maintenance of two receptors in the flies and mosquitoes (Diptera) was the result of a gene duplication event. Speciation of Anopheles mosquitoes affected receptor gene organisation and characterisation of AST-AR duplicates (GPRALS1 and 2) revealed that in common with other insects, the mosquito receptors were activated by insect AST-A peptides and the iCa2+-signalling pathway was stimulated. GPRALS1 and 2 were expressed mainly in mosquito midgut and ovaries and transcript abundance of both receptors was modified by feeding. A blood meal strongly up-regulated expression of both GPRALS in the midgut (p < 0.05) compared to glucose fed females. Based on the results we hypothesise that the AST-A system in insects shared a common origin with the vertebrate KISS system and may also share a common function as an integrator of metabolism and reproduction.
  
  
  CONCLUSIONS
  AST-A and KISS/GAL receptors and ligands shared common ancestry prior to the protostome-deuterostome divergence. Phylogeny and gene synteny revealed that AST-AR and KISSR emerged after GALR gene divergence. AST-AR genes were present in the hemichordates but were lost from the chordates. In protostomes, AST-ARs persisted and evolved through lineage-specific events and duplicated in the arthropod radiation. Diptera acquired and maintained functionally divergent duplicate AST-AR genes.
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Rute C
authors.initials: RC
authors.lastname: Felix
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Marlene
authors.initials: M
authors.lastname: Trindade
authors.affiliation: Centro de Malária e outras Doenças Tropicais, UEI Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008, Lisboa, Portugal.
authors.forename: Isa R P
authors.initials: IR
authors.lastname: Pires
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Vera G
authors.initials: VG
authors.lastname: Fonseca
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Rute S
authors.initials: RS
authors.lastname: Martins
authors.affiliation: Centro de Malária e outras Doenças Tropicais, UEI Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008, Lisboa, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Silveira
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Power
authors.affiliation: Comparative Endocrinology and Integrative Biology, Centre of Marine Sciences, Universidade do Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: João C R
authors.initials: JC
authors.lastname: Cardoso
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D020013:Calcium Signaling; D019143:Evolution, Molecular; D005216:Fat Body / Q000737:chemistry / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D049750:Genome, Insect; D005947:Glucose / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D010053:Ovary / Q000737:chemistry / Q000378:metabolism; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D044088:Receptors, Galanin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012098:Reproduction / Q000235:genetics; D016415:Sequence Alignment; D026801:Synteny
chemical_list: D019476:Insect Proteins; D043562:Receptors, G-Protein-Coupled; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D005947:Glucose