Molecular Genetics
DNA is made up of long strings of nucleotides. There are four nucleotides in DNA: Adenine (A), Thymine (T), Guanine (G) and Cytosine (C). These nucleotides are held together by a phosphate-sugar “backbone” and are complemented by a parallel strand of nucleotides making a DNA molecule “double-stranded”. Parallel strands are held together by hydrogen bonds between bases; Adenine binds to Thymine, Cytosine binds to Guanine. Discrete sections of DNA carry sequences of nucleotides that, when processed, are responsible for proteins or functional RNA chains. These sections are called genes. When making a protein, the DNA is first transcribed into a single-stranded piece of messenger RNA (mRNA) using an enzyme called RNA polymerase. The newly made mRNA is then translated through a ribosome into a long chain of amino acids. This chain of amino acids folds up to make a functional protein. Proteins build the organism, including all measurable and observable characteristics.
MC1R Gene
The Melanocortin-1-receptor (MC1R) gene can be found on chromosome 16 in mammals. Once transcribed from DNA into mRNA, the 951 base pair sequence is eventually translated into the respective MC1R protein with the assistance of a ribosome. This protein, which is a folded chain of 317 amino acids, can fulfill its role as a transmembrane protein.
When conducting genetic testing on Peromyscus polionotus, a team of Harvard Researchers uncovered a mutation present within the MC1R gene. A single nucleotide substitution at position 199 (cytosine to thymine) in the MC1R gene results in an inhibited function of the MC1R protein. This small difference causes a change in the amino acid chain produced by translation. Amino acid at position 67 within the polypeptide chain becomes a cysteine rather than an arginine. Meaning, mice with darker fur, that had a cytosine nucleotide at position 199, had an arginine amino acid at position 67. Mice with lighter fur, that had a thymine nucleotide at position 199, had a cysteine amino acid at position 67.
Wild Type & Mutant Alleles
Since the mice have two alleles of the MC1R gene, there are three possible options. They can either be homozygous, and have two ‘arginine’ (wild type) alleles; or homozygous, and have two ‘cysteine’ (mutant) alleles. The third option would be heterozygous, or one of each ‘cysteine’ (mutant) and ‘arginine’ (wild type) alleles.
Of the research conducted, it was discovered that of mice that were homozygous with two wild type alleles, all 126 had dark brown fur color. Of the 118 mice that were homozygous with two mutant alleles, 41% were light brown in color, 36% were medium brown in color, and 23% were dark brown in color. Of the 215 that were heterozygous, 81% had dark brown fur, and 19% had medium brown fur.
Wait… if the cysteine substitution codes for a light fur color phenotype, why weren’t all the mice with the homozygous mutant alleles light in fur color? This is because the MC1R gene is not the only gene that controls fur color within these mice. Like most traits, multiple genes are responsible for a phenotype. MC1R is one of the more influential genes when it comes to fur color in this situation, estimated to control somewhere between 10% to 40% of varying fur color.
