Independent Nonframeshift Deletions in the MC1R Gene Are Not Associated with Melanistic Coat Coloration in Three Mustelid Lineages

Abstract

Sequence variation within the 5' flanking (about 240 bp) and exon regions (426 bp) of the melanocortin-1 receptor (MC1R) gene was examined to determine the potential role of this protein in the melanistic coat coloration of 17 mustelid species in four genera: Gulo (wolverines), Martes (martens), Mustela (weasels), and Meles (badgers). Members of the genera Mustela and Meles, together with Martes flavigula and Martes pennanti, were shown to have intact gene sequences. However, several "in frame" deletions of the MC1R gene region implicated in melanism of other species were detected within members of the genera Martes and Gulo. For instance, Gulo gulo possessed a 15 bp deletion in the second transmembrane domain coding region, while Martes americana, Martes melampus, Martes zibellina, and Martes martes shared a 45 bp deletion overlapping this area. In addition, Martes foina was found to possess a 10 bp insertion followed closely by a 28 bp deletion immediately downstream of the deletion found in other martens. Notably, none of these indels was associated with a melanistic phenotype. Phylogenetic analysis revealed that each of these nonrandomly distributed deletions arose independently during the evolution of this family. Specific indel-neighboring motifs appear to largely account for the biased and repeated occurrence of deletion events in the Martes/Gulo clade.

Genetic characterization of Okinawan black rats showing coat color polymorphisms of white spotting and melanism

“…Melanocortin-1 receptor (Mc1r) and agouti signaling protein (Asip) (formerly genes E and A, respectively) are known to cause the melanistic form in a dominant and recessive manner, respectively (Feldman, 1926;Tomich and Kami, 1966). Both genes reportedly affect coat color changes in a variety of mammalian species (e.g., Vage et al, 1997;Eizirik et al, 2003;Hosoda et al, 2005;Kingsley et al, 2009). In a previous study of rats from the Otaru port on Hokkaido, where the dorsal agouti and black polymorphism exist, we found that the Otaru rats have the dominant system of melanism in which a single-nucleotide polymorphism (SNP) of Mc1r, i.e., a change from G to A at site 280 that leads to the replacement of glutamic acid with lysine in the amino acid sequence, causes the melanism (Kambe et al, 2011).…”

Comparative analysis of evolutionary modes in Mc1r coat color gene in wild mice and mustelids

“…In our previous study of mustelid carnivores (Martes and Mustela; Hosoda et al, 2005) we demonstrated that 'in frame' deletion events in mustelids are concentrated in a particular portion of the Mc1r gene and arise in association with specific nucleotide motifs (Hosoda et al, 2005); and further, that they are not associated with melanistic coat coloration. Interestingly, the 5' region of the Mc1r gene, which in other mammals hosts many functionally important single nucleotide polymorphisms (SNPs) and 'in frame' deletions (Eizirik et al, 2003;Mundy et al, 2004), in mustelids has a high nonsynonymous/synonymous substitution ratio (nearly 1, although this was estimated without correction for codon usage bias; Hosoda et al, 2005).…”

Evolutionary and phylogeographic views on <i>Mc1r</i> and <i>Asip</i> variation in mammals

“…In martens, the Mc1r coding region exhibits three independent length-modification events that resulted in a lack of a 15 bp, 18 bp, and 45 bp segment near TM2 and EC1 (Hosoda et al, 2005), whereas no such deletion or insertion events are visible in the other mustelid taxon, weasels. In-frame deletion events have been reported in other groups of mammals including domestic rabbits and jaguars (Fontanesi et al, 2006).…”

“…The in-frame deletion events in martens are concentrated in a particular portion of the Mc1r gene (i.e., EC1; Fig. 2A) and are thought to have arisen in association with specific nucleotide motifs, such as tandem repeats of two codons (6 bp) and an inverted repeatlike segment between the tandem repeats (Hosoda et al, 2005). It is plausible to presume that the emergence of such specific motifs could be the consequence of the above mentioned genomic constraints, and strong codon usage bias.…”