White people are mutants

Razib inspired me to share some of the story behind why white people are considered derivatives.

Reposted from the Classic Digital Bio.

No red herrings, here! Lamason et. al. found a single gene that controls human skin color while studying pigmentation in zebra fish (1).

These zebra fish had an unusual golden color that turned out to be an important clue. Lamason and collaborators found that the golden zebra fish lost their normal color because of a mutation in the slc24a5 gene. When the zebra fish have the mutant form, they produce fewer melanosomes.

A short language lesson
Fewer melanosomes, right. What on earth is a melanosome? Melanosomes are special compartments that store pigment, you can think of them like clear containers that hold brown paint. The brown paint would correspond to the pigment, melanin. There also different shades of brown paint (melanin), one lighter (phaeomelanin) and one darker (eumelanin). Melanosomes are only found in special kinds of cells called "melanocytes."

Fewer melanosomes mean a lighter color.

So what do we care about zebra fish?
We're very, very, very distant cousins and we share a common ancestor somewhere way, way, back in time. So, if zebra fish have this gene that controls melanosome production, humans probably have it, too. (Evolution is not controversial in my field; it's fundamental.)

So, just like all biologists have been doing for the past twenty some years, Lamason and friends went fishing off the GenBank (a database of nucleotide sequences), using the zebra fish gene as bait.

What did they catch?
They found the human version of the gene and looked to see if there were any differences that were associated with skin color. Indeed, there were. Europeans had the mutant gene (i.e. fewer melanosomes, lighter skin), while Africans had the gene that makes more melanosomes.

Other research
This isn't the first study to look at the genetics of skin color. Other researchers have run across skin color genes while studying cancer biology. Bonilla, et. al. found a single nucleotide change in the 3' untranslated region of the ASIP gene that is associated with skin color (2). (This changes the sequence of the messenger RNA but NOT the sequence of the protein). One nucleotide is associated with a lighter skin color, in Americans of African descent, with the other nucleotide, the skin color is darker.

The melanocortin 1 receptor (MC1R) also accounts for some variation in skin pigmentation and hair color (3). In this case, variation in the MCR1 protein results in red hair.

What do we conclude?
First, for those of you with a paranoid bent, your worst fears are confirmed. We can tell skin color with a simple genetic test. Hopefully, this ability won't be misused.

Second, the differences that determine skin color are very small. Statistically, it would seem that changing a few nucleotides in a 3 billion nucleotide genome, would be insignificant.

So it would seem.....

Read the abstracts from the original papers:

1. Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O'donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC. 2005. SLC24A5, a putative cation exchanger, affects pigmentation in zebra fish and humans. Science. 310:1782-6.

2. Bonilla C, Boxill LA, Donald SA, Williams T, Sylvester N, Parra EJ, Dios S, Norton HL, Shriver MD, Kittles RA. 2005. The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum Genet. 116:402-6.

3. Rees JL. 2004. The genetics of sun sensitivity in humans. Am J Hum Genet. 75:739-51.

technorati tags: biology, bioinformatics, race, DNA sequencing, zebrafish