Thursday, December 22, 2005

Happy hour: The color of our skin

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.


Vikrum said...

Hi Sunil,

Thanks for writing about this fascinating topic. You explain something which is complicated (at least to us non-scientists) very clearly.


Shruthi said...

I agree with Vikrum. You have explained it very well - and the topic being interesting - helps too!

Ashish Gupta said...

Excellent and lucid write-up Sunil.

I remember reading somewhere that coldness has something to do with skin colour. Colder the climate you live in, fairer you get. And we have observed people temporarily getting fairer/darker depending on how much time (reasonably long, say in months/years) they spend in Sun. So has this anything to do wit gene, or some other phenomenon?

Abi said...

Thanks for another excellent post, Sunil.

When I read "They took the human gene, and put it in to the golden zebrafish", it sounded quite fascinating. Is it easy to do? Perhaps you will explain how this sor ot stuff is done.

Thanks in advance.

Sunil said...

Vikrum, Shruthi, you're welcome.

Ashish.....i'm not in any way an expert in melanin signalling, but usually these signalling effects are complex. There definitely is a gene response (for just about any physiological process), and the sun's radiation turns on a bunch of different genes. Apparently the nature of radiation also has its effects. There are different types of Ultraviolet radiation (A and B), and it seems that UVA directly activates melanocytes (and increases pigmentation) but tanning is mostly caused by UVB, which does not directly increase melanin, but indirectly activates a bunch of pathways (altering the activity of many genes) resulting in more melanin finally. These processes are fairly complex, which is why biological processes are hard to study, since so many different events "talk" to each other.

But yes.......all physiological effects, in one way or another, will go down to some genes.'re welcome.

Actually, putting in genes of one species to another is not that difficult really. It also depends a lot on the model organism you're working with. Usually, you do this using DNA carrying elements (also DNA) called plasmids, where you put in your gene of choice, and then put the entire plasmid in to the organism you want to put it in to. If you want to put another gene in to Bacteria, it is simplicity in itself, and will take you less than a week. It gets more and more difficult as you go to "higher" organisms, but is fairly easy to do in worms (c. elegans), flies (Drosophila), yeast etc. Zebrafish are an excellent system to work with, as are frogs (xenopus), but here you do your modifications with eggs/embryos (where you inject RNA or DNA directly in to the embryo). So it's not too hard.

It's a little more work to do gene "knock-ins" in rodents, using plasmid vectors, but it is routinely done. A modern tool to get stuff in to mammals are "viral vectors" where you use viruses (with their virulence knocked-down) to which you tag along your gene of interest, to infect cells or tissues. The viruses are naturally very effective in getting in, and do so, but are non-virulent. So all they'll end up expressing is your gene of interest.

Perhaps i'll go in to the details of these processes in some post in the future.

zigzackly said...

Fascinating. And lucidly written. Off to trawl your archives now.

(Came here via DesiPundit, by the way.)

Sunil said...

Welcome to Balancinglife, Peter.

If there's ever a "CollaBlog" that you start on science, i'll be more than happy to be a part of it! :-))

Suhail said...

Very well written. Really makes it easy to understand. The very fact that I read through to the end of this article means it held my interest and I could understand atleast 50% of it. Usually I am the first one to run away from any Biology-types articles.
DNA/RNA, gene, vitamin, protein has been something which I could never comprehend, and embarassingly at that. Still do not..but never late to make an attempt, wot say?
(ps:yes, I am BACK for good, hopefully :-)

Anonymous said...

That was fascinating!

East Asians (Chinese, Japanese, Koreans etc) are light skinned.
I find it interesting that we Indians have colour from one end of the spectrum to the other.

Have you heard of the Genographic project, where they try to trace the migratory route of one's ancestors based on the genes?

Sunil said...'s a fascinating field, and searching will reveal a lot of answers about us humans, so don't be shy to read about it.

Srikanth, thanks. It's not surprising at all that Indians spread across the human color rainbow. It's the same with much of the Mediterrainian countries, as well as Iran and Central Asia. And it's because these regions have been right at the center of human activity, with all races flocking in (as migrants or invaders) and which will result in a highly mixed and diverse population. India itself has had it's Indus civilization, the Dravidian cultures, Aryan migration, Greek invasion, invasions by Huns, Kushans, Shakas, then Arabs, Turks and Tajiks, Mongols, then the Europeans.......there's little doubt that the populations have to be highly mixed.

I have indeed heard of the Genographic project.....though i don't know any of it's details, or what its final goals are.

Anonymous said...

excellent post! very well explained..

pippala leaf said...

Excellent post Sunil. I agree with AshishG's observation. Your post explains why people from southern India (where heat and humidity is high) tend to have darker skin. Thanks again for these kind of posts.

apu said...

Thanks Sunil - infact I remember reading about this discovery in the newspaper, butyour post was far more lucid!

Sunil said...

Thanks Sue, Apu.

Madhu.......that's a very, very simplistic explanation, and not really true. A lot of non-punjabi, non-kashmiri "North Indians" are rather dark. And if you go a little towards the east (Bihar, Bengal), the people are in general darker. On the other hand, a lot of South Indians are rather fair. So, these simplistic explanations don't hold good....especially since this evolution has taken thousands of years to happen, not just a few years. And India is a real melting pot of races....:-)

Anonymous said...

As you said, this topic was covered on the evening news on TV. I happened to miss it, and am really glad that I got to read about it on your blog.
Just curious, is science your major in academics.
nice post...

Sunil said...

yes Rajeshwari..i'm a scientist. I'm a researcher in the biomedical/biochemical sciences, and hope to wrap up my phd in the next few months.

Anonymous said...

hi sunil im extremely interested in what i've just read, pls let me know if ur phd concerns some of the same research.....

Anonymous said...

If you do more research on melanin, you'll find that all ethnicities have SAME AMOUNT of melanin, but it's the size of melanin that differentiates darker skin tone from light skin tone.
The fair skin tones of many northern Europeans have nothing to do with living in colder climate. As you know, Siberians, Inuits and Tungus people live in much colder climate and they have slightly darker skin pigment. The reason? Norhern Europe is very overcast and there's much less penetration of UV rays than in northern Asia.

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