It’s not that I’m at them, but there are lots and lots lying around. Papers in horizontal and vertical orientation on both sides of my laptop, each vying to get my attention, each important. Or at least I thought so when I piled them there.

So, I feel like I owe readers of this blog a follow-up post entitled “A Dark Horse II” in which I get to write about the article that initially inspired me to write part I, but which I didn’t have the time to get to, even then.

Dilemma: do I, or don’t I, write it? Or do I just punt and link to the article in PLoS Genetics about the golden horse coat color entitled “champagne dilution”?

The mutation responsible for the champagne horse color is in a protein that binds and carries glycine into the cell under acidic conditions, or gets it out of acidic subcompartments called lysosomes. Alanine, proline, and the neurotransmitter GABA as well. [The rest is biochemistry, and I am really grateful to biochemists for doing what they do, because I can’t get that interested.]

The horse mutation doesn’t stop the protein, Slc36a1 (what a name!), from working. It just swaps one component amino acid for another, thereby reducing in some way the quantity of red and black pigment that gets made by the melanocytes (pigment cells) in the skin and at the base of hair follicles.

Many horse breeders value animals with variation in coat color. Several genes are known which diminish the intensity of the coloration and are phenotypically described as “dilutions”. Two of these are a result of the Cream (CR) locus and Silver (Z) locus. The molecular basis for Cream is the result of a single base change in exon 2 of the Slc45a2 (Solute Carrier 45 family A2) gene […] The Silver dilution is the result of a missense mutation of Pmel17 (Premelanosomal Protein) […] and affects only [black] eumelanin, causing little to no visible change in the amount of [red] pheomelanin regardless of zygosity. The change in eumelanin is most apparent in the mane and tail, where the black base color is diluted to white and gray.

Doesn’t that sound attractive? As for the champagne dilution, which you can add to a number of genetic backgrounds in the horse, you can see examples in the article (Figures 1 and 2).

A similar approach in the golden zebrafish led to the identification of a more effective mutation in the Slc24a5 gene (yes, you guessed it, Solute Carrier 45 family A2) by Lamason and co-workers. Effective in that the protein doesn’t work, and when it doesn’t, intracellular calcium transport does not either. Okay, it was not the intracellular calcium that got this paper into Science, but the followup. A more minor mutation, or variation, of the same gene exists in humans, and correlates with population skin color. One variant is more frequent in dark-skinned populations, while a more recent evolutionary variant is more frequent in light-skinned populations.

Variation of skin, eye, and hair color in Europeans, in whom [the same SLC24A5 variant] predominates, indicates that other genes contribute to pigmentation within this population. For example, variants in MC1R have been linked to red hair and very light skin [reviewed in (37)], whereas OCA2 or a gene closely linked to it is involved in eye color (7, 38). The lightening caused by the derived allele of SLC24A5 may be permissive for the effect of other genes on eye or hair color in Europeans.

So I am still curious about why a pigment cell needs calcium and proline, glycine or GABA in the little compartments that contain melanin. But once more out of time. Maybe I’ll get around to white blotches on the face and belly in a future installment, which subject is far closer to my current preoccupations in any case.