White people are mutants
50 points for digital biology! Lamason et. al. found a new gene that controls human skin color while studying pigmentation in zebra fish (1).
No red herrings, here! 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.
Subject: Doing biology with bioinformatics
No red herrings, here! 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.
Subject: Doing biology with bioinformatics
posted by Sandra Porter at 11:38 AM
4 Comments:
Thank you for confirming something I've always known: I am a mutant!
Actually, please clarify one of your statements: 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. How can the mRNA be changed but not the protein if you have a different phenotypic effect (i.e., lighter vs. darker skin)?
Dear Anonymous,
We're all mutants in some way, we just didn't know it until the our genome got sequenced. ;o)
As your question about RNA. To repeat the question, you asked why a change in the mRNA, that doesn't affect the structure of the protein, would lead to a change in skin color?
The answer is, I don't know. But I can speculate. The most likely explanation is that this mutation does something to change the concentration of mRNA. If we have less mRNA, we probably have less protein.
Since this mutation maps in the 3' untranslated region of the mRNA, it might have an effect on some of the things that happen to mRNA between the time that it gets made and time that it gets exported out into the cytoplasm and translated.
There are a few different things that this mutation might do. It might decrease the efficiency of polyadenylation, since that happens at the 3' end; it might somehow effect export from the nucleus, or it might decrease the stability of the mRNA. RNA folds into all kinds of wild structures. Changing one base might change the ability to form one of those structures.
Very interesting, specially the serendipity in it: Zebra fish gene BLASTed and human gene around.
"We can tell skin color with a simple genetic test" Michael Jackson start crying!!
Is this related at all to albinism? Thanks.
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