Skin Color Genetics

Eumelanin is a dark, natural pigment found in human’s skin. It is responsible for the shade of skin color that an individual may have; a greater amount of eumelanin production correlates with darker skin, and a lesser amount of eumelanin would correlate to lighter skin. Whereas eumelanin is responsible for the shade of skin color, pheomelanin is the pigment responsible for the hue of skin color, such as yellows, reds and browns. As many things, an individual’s skin color is determined by genetics. This module will discuss the production of eumelanin in 3 steps, as well as introducing where some problems in the pathway could potentially arise.

Step 1

The pathway to eumelanin production is intricate and complex, and contains many molecules. To begin, an abundant amino acid referred to as tyrosine is transported into the melanosome organelle (which is found in the melanocyte) with the help of the protein OKA2. With the help of proteins SLC24A5 and SLC45A2, which are responsible for regulating the concentration of ions within the melanosome that are vital for eumelanin production, tyrosine comes into contact with an enzyme called tyrosinase, and in the presence of oxygen is turned into dopaquinone.

 

tyrosine + tyrosinase + oxygen = dopaquinone

Step 2

Melanocytes contain a transmembrane protein called melanocortin-1-receptor, also known as MC1R. When this transmembrane protein interacts with molecules on the outside of the melanocyte, it stimulates MC1R to alter its shape, which in turn signals the melanocyte to begin a handful of biochemical reactions. This in turn leads to the production of cyclic adenosine monophosphate, or cAMP. However, the amount of cAMP that is produced varies; for example a mutation that alters the MC1R protein could affect the melanocyte’s ability to create cAMP. Another protein called the Aguti Signaling Protein, or ASIP, that is capable of binding to the MC1R protein, which can then render the MC1R protein incapable of signaling for cAMP production. 

When there are excess amounts of cAMP, dopaquinone will convert into a molecule known as dopachrome. However, if there are limited amounts of cAMP that is produced within the melanocyte, then pheomelanin will be produced.

dopaquinone + excess cAMP = dopachrome

OR

dopaquinone + limited cAMP = pheomelanin

Step 3

Dopachrome is capable of breaking down into 5,6-dihydroxyindole (DHI). However, it also is able to produce 5,6-dihydroxyindole-2-carboxylic acid (DHICA) when coming into contact with the enzyme dopachrome tautomerase (DCT). 

dopachrome = DHI

OR

dopachrome + DCT = DHICA

At this stage, DHI and DHICA, of which are both monomers, conjoin to form the eumelanin polymer chain.

DHI + DHICA = eumelanin

Pathway Interruptions

However, it should be noted that this isn’t always what occurs; mutations that inhibit the proper function of proteins such as tyrosinase, or DCT, or others can link to the inability to produce pigment, like albinism. If there is a mutation within a gene or the presence of another agent (like ASIP) that inhibits the production of eumelanin, it can disrupt the pathway and lead to little or no eumelanin being produced. 

As previously mentioned, the process of eumelanin production is quite complicated and consists of many moving parts. And all it could take to disrupt the eumelanin production process is to inhibit just one of those moving parts, whether it be tyrosine, cAMP, DHI, or many others.