Molecular evolution of the pigmentation gene melanocortin-1 receptor in rodents

Abstract

ABSTRACT. Adaptive variation in the melanocortin 1-receptor gene (MC1R), a key locus in melanogenesis, has been identified in some species of rodents. However, in others, MC1R has no causative role in pigmentation phenotypes despite their coat color variation. In this study, we characterized the rates and patterns of MC1R nucleotide and amino acid sequence evolution and, particularly, selective pressures in the separated domains of the protein using a comparative analysis of 43 species representing three major lineages of rodents with variable coat colors. We found high amino acid variation (44% of sites) throughout the protein. Most substitutions were observed in extracellular and transmembrane domains; the intracellular segment was conserved across species. Pairwise non-synonymous substitutions did not vary significantly in different domains among the rodent lineages -i.e., variation was not associated with phylogenetic distance. Phylogenybased likelihood analysis suggested that purifying selection has mostly shaped the evolutionary course of MC1R. However, a high proportion of sites (27%) were under relaxation of functional constraints (ω = 0.38), and four sites (3, 14, 26, and 251) clearly evolved under positive selection (ω ≅ 2.9). Thus, our data indicate a high proportion of sites evolving under relaxed evolutionary constraints, which might indicate the evolvability of the system in the generation of adaptive changes in specific taxa in rodent lineages.

Endothelin Receptor B2 (EDNRB2) Gene Is Associated with Spot Plumage Pattern in Domestic Ducks (Anas platyrhynchos)

“…It is noticed that no destructive or even lethal effects of this gene were observed in duck and the identical situation is found in chicken and quail mutants [ 13 , 14 ]. We can speculate that the Arg332His substitution found in EDNRB2 is a neutral mutation which is not harmful for surviving or reproduction in spite of possible strong selective pressure in the wild [ 1 , 38 ]. Variation in EDNRB2 sequences is able to help us to infer phylogenetic and phylogeographic relationships among organisms, assess the adaptive evolution of plumage color and understand gene evolution and evolutionary history of aves [ 39 , 40 ].…”

Mouse models for V103I and I251L gain of function variants of the human MC4R display decreased adiposity but are not protected against a hypercaloric diet

“…Interestingly, the melanocortin 1 receptor gene ( MC1R ), paralog and ancestor of MC4R , is also polymorphic in its coding region and produces heritable gain of function variation with functional adaptive consequences [ 47 , 48 ], as found in several wild mouse populations that underwent an evolutionary darkening of their dorsal pelage after sandy rock terrains transitioned to black cooled lava flow lands following activity of nearby volcanoes [ 49 ]. The newly established darker landscape was likely to exert selective pressure for the fixation of novel Mc1r mutations that promoted the production of dark eumelanin-stained hairs restoring camouflage adaptation against visual predators, such as hunting owls.…”

Mouse models for V103I and I251L gain of function variants of the human MC4R display reduced adiposity and are not protected from a hypercaloric diet

“…Interestingly, the melanocortin 1 receptor gene ( MC1R ), paralog and ancestor of MC4R , has also shown to be polymorphic in its coding region and to produce heritable gain of function variation with functional adaptive consequences [47,48]; as found in several wild mouse populations that underwent an evolutionary darkening of their dorsal pelage after sandy rock terrains transitioned to black cooled lava flow lands following activity of nearby volcanoes [49]. The newly established darker landscape was likely to exert selective pressure for the fixation of novel Mc1r mutations that promoted the production of dark eumelanin-stained hairs restoring camouflage adaptation against visual predators such as hunting owls.…”