title: A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss).
abstract: In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity.
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, NO-1430 Ås, Norway.
authors.forename: Uniza Wahid
authors.initials: UW
authors.lastname: Khan
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, NO-1430 Ås, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Øverli
authors.affiliation: University of Rochester Medical Center, School of Medicine and Dentistry, Department of Pharmacology and Physiology, Rochester, NY 14642, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hinkle
authors.affiliation: KAUST catalysis center (KCC), King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
authors.forename: Farhan Ahmad
authors.initials: FA
authors.lastname: Pasha
authors.affiliation: Department of Molecular Biosciences, University of Oslo, NO-0316 Oslo, Norway.
authors.forename: Ida Beitnes
authors.initials: IB
authors.lastname: Johansen
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, NO-1430 Ås, Norway.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Berget
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, NO-1430 Ås, Norway.
authors.forename: Patricia I M
authors.initials: PI
authors.lastname: Silva
authors.affiliation: Norwegian School of Veterinary Medicine, Institute of Basal Sciences and Aquatic Medicine, NO- 0033 Oslo, Norway.
authors.forename: Silje
authors.initials: S
authors.lastname: Kittilsen
authors.affiliation: Technical University of Denmark, National Institute of Aquatic Resources, DK-9850 Hirtshals, Denmark.|Norwegian Institute for Water Research (NIVA), NO-0349 Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Höglund
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, NO-1430 Ås, Norway.|NTNU - Norwegian University of Science and Technology, NO-7491 Trondheim, Norway.
authors.forename: Stig W
authors.initials: SW
authors.lastname: Omholt
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, NO-1430 Ås, Norway.
authors.forename: Dag Inge
authors.initials: DI
authors.lastname: Våge
mesh_terms: D000818:Animals; D015870:Gene Expression; D005786:Gene Expression Regulation; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D017686:Oncorhynchus mykiss / Q000502:physiology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D058261:Receptor Activity-Modifying Proteins / Q000378:metabolism*; D044103:Receptor, Melanocortin, Type 2 / Q000096:biosynthesis*; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D050505:Mutant Proteins; D012333:RNA, Messenger; D058261:Receptor Activity-Modifying Proteins; D044103:Receptor, Melanocortin, Type 2; D011979:Receptors, Pituitary Hormone; C029446:MSH receptor