Results and Discussion
The MC1R gene was determined to be the gene responsible for the dark mutation. (The dark mice are a mutation of the light mice with a dark coat with unbanded hair.) The information about the unbanded hair was a starting point for marking the genes to see what genotypes were actually responsible for the dark phenotype. Although agouti may be involved, it is not directly related to the phenotypic differences. Four amino acid mutations were located on the MC1R gene as follows: Arg-18-->Cys, Arg109-->Trp, Arg160-->Trp, Gln233-->His. These mutations presented in the Pinacate dark mice show a direct genotype to phenotype association. One or more of these mutations cause the light and dark coats on the mice.
Another possible reason for the coat color variations is population structure.
If the mice engaged in non-assortative mating, or mated with only like mice, differences in the coat color could easily be perpetuated. Thus, random coat differences can occur within a population even when there is not a gene responsible. However, these mice are known to engage in assortative mating.
To determine whether population structure was a major factor, mitochondrial DNA was sequenced and it was determined that light and dark mice interact with each other. Therefore there is no evidence for population structure causing the color differences. This reinforces the fact that one of the four mutations above is indeed responsible for the mutation. The fact that there is random mating and there are differences mean that there is a gene responsible for the differences in coat color.
The genetic mutations that relate to mouse coat hair color cause a change in charge of associated amino acids. Four different amino acid regions were found to be connected to mouse coat hair color. Three of these showed a change in charge from positively charged arginine to an uncharged amino acid. The fourth amino acid region had an uncharged glutamine that was replaced by a positively charged histidine. All four of these mutations were found in regions of the Mc1r receptor which are probably involved in interactions with other proteins.
In addition to the finding about the change in amino acid charge, Nachman et al found that the allele for dark coat hair color is dominant over the allele for light mouse hair color. In the mice studied in the laboratory, mutations in the Mc1r receptor which caused loss-of-function were found to be recessive – resulting in light color. Mutations resulting in gain-of-function in the Mc1r receptor were found to be dominant, causing dark color.
Nachman et al also found that the pattern of variation in nucleotides in the Mc1r alleles from mice at the Pinacate study site indicates recent positive selection. Positive selection, often referred to as directional selection, occurs when natural selection favors a single allele – leading allele frequency to continuously shift in one direction. The idea of directional selection was a major theme of the well-known peppered moth study, a classic example of natural selection in action (see references for a link to information about this important study). Nachman et al found that the level of nucleotide diversity among alleles coding for light coat color was greater than the level of nucleotide diversity in alleles coding for dark coat color.
Nachman et al found that their data does not allow them to determine the effects of the four previously mentioned amino acid sites on coat color. They also found that the amino acid changes occurred in the Mc1r receptor among the mice from the Pinacate study site but not from the Armendaris mice. They suggest that this finding indicates that a similar dark phenotype has evolved independently and via different genetic changes. Nachman et al conclude by stating that Mc1r darkening mutations have also been found in other species. Ecological factors, such as predation, may have an effect on changes in observed population frequencies.
|
|