How do we know the genetic code? (Part 1)

Over the course of the next few posts, I hope to tell you the story behind one of the most important codebreaking efforts in history.  The code at the center of this story does not concern itself with assassination conspiracies or terrorist plots.  There is no political intrigue or corporate espionage.  No couriers are relieved of their parcels (or their lives) during a clandestine midnight ride.  The code of which I speak isn’t really much of a code at all; its message can be read in the very faces of those who carry it.  And every single one of us, and everyone we know or have ever known or will ever know, carries this code with us.

The field of genetics offers a host of contrasts.  In the race for survival, our genes confer upon us great assets while simultaneously saddling us with numerous liabilities.  Genes place strict physical constraints on what a particular individual can and can’t do, and yet if a situation is even remotely advantageous to survival, we can be almost certain that somewhere, some organism has the genes to exploit it.  Our genes are–with the exception of identical twins–uniquely ours, and yet all of us, from the mightiest sequoia to the most insignificant cyanobacterium, are built using the same basic four-letter code: A, T, C, G.

It’s no easy feat, turning four letters into millions of species.  So in this post and the next, I’m going to do something I don’t often do:  I’m going to explain, in detail, what we know about the genetic code.  I’ll leave the explanation of how we know what we know for subsequent posts.

 Behind blue eyes

Most of us have a passing familiarity with genetics, whether we realize it or not.  We understand that tall parents tend to produce tall kids.  We understand that those “family history” questions that we answer when we go to get life insurance are, in some sense, a quick and dirty genetic test.  We know that genes define relationships within and across species:  a dog-wolf hybrid seems more realistically achievable than a dog-cat hybrid (or a dog-shrimp hybrid, or a dog-mushroom hybrid, etc.).  And when we go to school, we’re taught that all these basic observations about the world around us are due to something called DNA.  But what is DNA?  And what does possessing a certain kind of DNA have to do with my having blue eyes?  Wait a sec, why are my eyes blue, anyway?  (For the record, my eyes are green.  But assuming blue eyes simplifies this discussion considerably.)

Axl Rose once said, “She’s got eyes of the bluest skies.”  I wonder if he knows how close to the truth he actually was.  See, humans only have one pigment in their eyes–melanin–and it’s brown.  So, unless you’re albino, in which case you have no pigments, your eyes are brown.  But people with blue eyes have much less of this brown pigment than people with brown eyes do.  When light reflects off a blue-eyed person’s iris, there’s really only enough pigment to absorb the reddish tones of the visible spectrum.  The rest of the light is scattered and reflected away.  Looking at your standard visible spectrum (also known as a rainbow)…

…we see that once you absorb the reddish colors, most of the colors left to scatter are on the blue end of the spectrum.  That’s why eyes can have brown pigmentation and yet appear blue.  As a side note, this preferential scattering of blue light is known in the scientific community as Rayleigh scattering, and it’s also the reason why the sky is blue:  air molecules preferentially scatter blue light as well.  So yes, Axl, her eyes are in fact the same color as the sky.  But the point is that blue-eyed people and brown-eyed people both have the same pigment:  melanin.  It’s just that blue-eyed people have less of it.

So less melanin → bluer eyes.

But what causes someone to have less melanin?  Well, melanin in the body is made from a specific amino acid called tyrosine.  The less tyrosine you have, the less raw material your body has to work with in making melanin.

So less tyrosine → less melanin → bluer eyes.

But how can you get less tyrosine?  After all, you constantly replenish amino acids by eating, and your body makes some on its own.  So shouldn’t your eyes get bluer after a big meal?  Not quite.  Your body has specialized cells that make melanin from tyrosine.  In order to make melanin, the tyrosine has to gain entry into those cells.  And those cells are pretty exclusive.  They’ve even got a big-ass bouncer at the entryway named “P protein.”  How P is feeling will determine whether the tyrosine gets into the cell tonight or not.

But the picture of P as a bouncer is a little misleading.  P is what’s called an integral membrane protein, and far from just being the bouncer at Club Melanin, P is actually the doorway itself.  And any given melanin-making cell will have multiple P proteins dotting its surface–multiple entryways into the cell.  The more P proteins there are, the more tyrosine can get into the cell, making more melanin and, in turn, making the eyes darker.

So fewer P proteins → less tyrosine → less melanin → bluer eyes.

But what causes a cell to have more or fewer P proteins?  It turns out there’s another protein called HERC2 that basically acts as a dimmer switch to turn up or down the production of P proteins.  HERC2 comes in a few different varieties, one of which is pretty rare.  That rare version just happens to dim P protein production down to the “blue-eyed” level.

So rare HERC2 protein → fewer P proteins → less tyrosine → less melanin → bluer eyes.

But what causes someone to have the rare version of HERC2?  Now we’re finally getting somewhere:  the flavor of HERC2 that you possess is determined by patterns in your DNA, specifically a short section of your DNA known as a “gene.”  The HERC2 gene is a series of letters (A, T, C, and G, as mentioned before) that encodes what kind of HERC2 your body produces.

So specific HERC2 gene in our DNA → rare HERC2 protein → fewer P proteins → less tyrosine → less melanin → bluer eyes.

I did this little demonstration because most people assume that your DNA somehow mysteriously reveals itself in your outwardly visible traits (or, in some unfortunate cases, in your medical history).  People are usually surprised to see how far removed our DNA actually is from, e.g., our eye color.

What is the genetic code?

At this point, you might be saying, “You’ve been yammering on about blue eyes for a while now and at no point have you mentioned anything about the genetic code you’re supposedly going to break for us.”  Actually, I have mentioned it, although I might have intentionally obfuscated it just a touch.  Looking back at our equation for blue eyes:

Specific HERC2 gene in our DNA → rare HERC2 protein → fewer P proteins → less tyrosine → less melanin → bluer eyes

we saw, albeit very briefly, that a little bit of biochemistry or physics got us from one concept to the next.  So if we wanted to hand-wave, we could just say, e.g.:

1.  Fewer P proteins

2.  ???????????? (biochemistry)

3.  Profit! (Less tyrosine)

Each one of those arrows up there is probably several Ph.D. dissertations worth of work, but for the next few blog posts, we’re really only concerned about one of the arrows.  Curiously, it’s the one that I explained in the least detail, and for good reason:  it’s the most important one.  It’s the arrow between “Specific HERC2 gene in our DNA” and “rare HERC2 protein.”  How do we go from a specific series of letters in our DNA to a protein that functions and contributes actively to our biochemistry and even to our outward appearance?  The answer to that question is the genetic code.

As you can see, it took a whole blog post just to define the term we hope to explain.  This is a big topic, so it’s going to require several posts.  Next time, I’ll actually explain the biochemistry behind the genetic code.  We’ll look at what DNA is, what proteins are, and how they interact.  After that, I’ll get into the details of how all of this craziness was discovered (short answer: lots of grad students working lots of late nights).  This is pretty intense stuff, so if understanding doesn’t come at first, feel free to ask questions or make comments if I need to clarify things.  But I encourage you to stick with me while I explain the genetic code; it’s one of the most interesting and important pieces of science from the last century.

Leave a Reply

Your email address will not be published. Required fields are marked *