It’s time to vociferously discuss some science again, over a mug of beer (or a fortifying orange juice, or any other stimulant of your choice). This story even made it to some news sites, only because it seems to be important to too many people. But the science is fascinating, and the experiments very well thought out, so why not bring it out on Balancinglife?
Yup, this post’s all about the color of skin. A lot of us know that different skin color is due to different amounts of the pigment melanin. This pigment is produced in the skin by cells called melanocytes, and stored in structures called melanosomes. Quite obviously, Africans have tons of melanin, white Europeans have very little, and lots of the rest have some thing in between. But it wasn’t clear at all how this happened, and what controlled it.
But there’s been some breakthrough research recently. And this knowledge didn’t come to us from human patients, but from some humble fish. Clearly, fish aren’t only important as food that increases human lifespan (and making the mind sharp, at least in Bertie Wooster’s opinion). The fish studied are a very popular lab too, called zebrafish that are supremely easy to manipulate genetically. They’re called zebrafish for obvious reasons. They have deep, rich stripes running across themselves, not unlike those striped horses of the savannah. Now, some researchers noticed something odd. There’s a known strain of zebrafish called golden, which are lightly colored, and have much lighter lines running across them. These fish have “hypopigmented” melanophores (a lot less melanin) compared to the “wild type” or normal zebrafish, and the development of melanin pigmentation is delayed in these golden zebrafish. So a bunch of researchers started looking at this more closely.
Interestingly, the melanosomes of these fish looked a lot like the melanosomes of light skinned humans. So they figured that the gene causing this “golden” effect would be somehow responsible for skin color. And so they did some nice genetics (positional cloning and morpholino knockdowns, which we won’t get in to), and identified a specific gene. (image from Science, 2005, 310, 5755, pp. 1782 - 1786)
Blink. Take a deep breath.
Now, as a refresher for those who forgot, a gene (DNA) is made in to RNA, which then gives rise to a protein. This protein is the actual functional unit that carries out the action. Proteins are made up of scores of building blocks called amino acids, and we’ll get back to these in a moment. Now, how do you prove that this gene is responsible for color in normal zebrafish? Simple, take the gene, and put it in to the golden zebrafish and see what happens. The researchers did exactly that, and found that the normal gene, once introduced in to golden zebrafish fully restored normal color to these fish. Clearly, this gene plays a major role in skin color.
But what does that have to do with us, you ask? The researchers asked the same question, and mined the human genome for genes that looked like this fish gene. The found a gene, SLC24A5, in humans, where 69% of the amino acids were identical to the fish gene, suggesting with little doubt that it was the human version of the same gene. Now here comes their most convincing experiment.
They took the human gene, and put it in to the golden zebrafish. Guess what? The golden zebrafish regained their normal color. The human gene was fully functional in fish, and worked to regulate color, proving with out doubt (one of) it’s functions.
There remained one obvious question. Did this explain different colors in humans? The researchers then looked through different human populations to see how this gene was different in them. They looked for “polymorphisms”, differences in the human gene in different populations. And the found one. Almost all Africans, native Americans and Asians (93-100%) have an amino acid called Alanine in a certain position in this gene. Almost all white Europeans had another amino acid called Threonine there, in that exact same position in the gene. And this can happen with just one single mutation in the DNA of the gene, a change of just one single base (out of thousands). And African Americans of mixed ancestry showed the same statistics, with the fairer ones having a greater prevalence of the Threonine mutation.
But the story remains incomplete (isn’t that the beauty of science? One discovery leads to more questions). East Asians (Chinese, Japanese, Koreans etc) are light skinned. But almost all of them shared the same allele as the Africans. So, in their case, there seems to have been a second selection (of some other gene, that’s still unknown) that’s resulted in lighter skin.
All this however still doesn’t tell us why light has been preferred. It is well known that dark skin protects the skin against ultraviolet damage, an obvious protection in harsh, sunny climes (Africa). But for light skin the most plausible hypothesis (still unproven) is that it allows more absorption of sunshine (required to make Vitamin D) in regions where there is little sun, requiring some “positive selection” of a gene for this purpose.
A nice bit of work, using a model organism (in this case a fish) to answer human questions, and elegantly illustrating natural selection and evolution in an everyday system.