Why are men the colorblind ones? (Vertical Integration Part 1: Biology)

“Vertical Integration” is a classic business concept, most notably used by Andrew Carnegie’s steel company. It occurs when a company buys several levels of supply and distribution of its product; for instance, a steel processing company may also buy the ore mines and the railroads to distribute its steel.

School subjects are taught horizontally. Students take biology classes, where they learn about many different aspects of biology, but hardly ever go into a deeper, vertical understanding of how these phenomena occur. A student may learn the nuances of the subject one level down (biologists learning chemistry, or chemists learning physics, or physicists learning math), but hardly anyone goes all the way down.

That is the point of the Vertical Integration series. Instead of taking a broad subject and going horizontally, I will take one single topic and go down, down, down on this elevator until I understand exactly how it works. The topic:

Why are men so often colorblind?

The Short Answers:

Why are males more often color blind than females?

Males have one X chromosome and one Y chromosome. Females have two X chromosomes. Red-green color blindness is recessive, and the gene for it is on the X chromosome. If men get it on their X chromosome, they have it. But women need to get two copies, one on each X, in order to be color blind.

What makes a gene recessive?

Recessive genes are broken or damaged versions of a gene that essentially aren’t doing anything. Dominant genes function well. A songbird with broken vocal chords will be drowned out by birds with loud voices.

What makes a gene “broken”?

Genes themselves don’t do much. Being “broken” doesn’t mean that the DNA is cut or anything, but there are many steps needed to put a gene into action. When one of those steps does wrong, the gene has no effect on its host. For instance, RNA polymerase is the enzyme responsible for starting a gene down its path to having a voice. But in many broken genes, RNA polymerase can’t bind to the DNA and start that pathway.

 

The Long Answers:

Why are men more often color blind than women?

Advanced Explanation:

The vast of your DNA is contained in chromosomes, long pieces of DNA that contain many different genes as well as non-coding (non-gene) regions. Unless you have a genetic condition like Down Syndrome, you have 46 chromosomes, 23 inherited from your mother and 23 inherited from your father. The first 44 chromosomes are just called “2 Chomosome #1s, 2 Chromosome #2s, 2 Chromosome #3s” all the way to “2 Chromosome #22s.” But the 23rd chromosomes? Those are your sex chromosomes, meaning they determine your biological sex. Again, unless you have a genetic condition like Trisomy X, you have two sex chromosomes. Females have two large X chromosomes, and males have one large X chromosome along with one tiny Y chromosome.

You may be familiar with dominant and recessive genes: you have two copies of each gene (one from mother and one from father), and recessive gene copies can only shine through when you have no dominant copies of that gene. Normally, this means that you need two recessive copies: one from mother and one from father.

However, you only need two recessive copies when you have two copies of the gene. The X chromosome is immensely larger than the Y chromosome, and therefore has far more genes. Since the X chromosome has no chromosome to match with inside of a male body, that means that a large number of those genes only have one copy. Therefore, to have a recessive trait, you only need one recessive gene copy, because there’s no room left for a dominant copy.

There are many different kinds of colorblindness, but the most well-known is red-green colorblindness (you can’t tell red and green apart). Red-green colorblindness is far more common in males than in females. This is because the colorblindness is the recessive version of the red-green color gene, and the gene is on the X chromosome with no match on the Y chromosome. For a female to be colorblind, she needs two colorblind versions of the red-green gene, one for each X chromosome. If she has even one “color” version of that gene, she will not be colorblind. But in males, there is only one slot for the gene; therefore, to be colorblind, all they need is a single copy of the colorblind version.

Thus, males are more often colorblind because they have no second chances: they either are colorblind, or they aren’t, whereas females can still inherit one colorblind copy of the gene and have a backup.

For more info and exceptions to the above paragraphs, please look into: mitochondrial DNA, chromosomal abnormalities, intersex, androgen insensitivity syndrome, genetic inhibition, epistasis, and incomplete dominance. 

Explain It Like I’m 5:

Your DNA is organized into 46 strands called chromosomes. You get 23 from each parent. 22 of those chromosomes have a perfect match from the other parent (44 in total). The two chromosomes left (#23 from mom and #23 from dad) are called sex chromosomes, because your sex is based off of which copies of each you get. Females got two X versions of that chromosome, whereas males only got one X version (plus a Y version to make two sex chromosomes in total). But the Y version is much smaller than the X version, so it can’t fit as many genes onto it.

In short, the gene that determines whether or not you have red-green color vision is located on the X chromosome and not on the Y chromosome: females have two gene copies and males only have one. People who are red-green colorblind only have the colorblind version of the gene, which is recessive. But females, with twice as many X chromosomes, are twice as likely to get at least one color-vision copy of the gene, which is dominant. A female with one colorblind copy of the gene can still keep her red-green vision if she has a backup, but a male with one colorblind copy will always be colorblind.

Chromosomes are like bins because they can contain many things at once, but they do have a limit. Imagine that to have color vision, you need to have a working magnifying glass, but it can only be put into the X chromosome bins. If you’re male and find that there is a broken magnifying glass in your only X bin, then you’re tough out of luck. Because of that broken magnifying glass, there’s no room for a working one, and you don’t have another bin to put a working one into. For females, by contrast, having a broken magnifying glass in one X bin is not the end of the world because you have that other X bin to put a working one in. You only need one proper magnifying glass, after all (because color vision is a dominant gene). A female will only be denied magnifying pleasure (color vision) if both of the X bins contain broken magnifying glasses. That’s much less likely than having just one broken one.

What makes a gene recessive?

Advanced Explantion:

This question was the inspiration for this series. All throughout middle school and high school, diseases and blue eyes had been explained to me as “there are two recessive copies of the gene.” But, somehow, I never thought to ask the question, “What is a recessive gene?” A gene that’s recessive? Good job, Sherlock. Why is it recessive?

In short, a recessive copy of a gene is a broken or damaged copy. It doesn’t show because it isn’t doing very much. My eyes are blue because they’re not making a lot of brown pigment, so nothing shows up. Your eyes may be brown because you have at least one gene making pigment and picking up the slack for that lazy, broken blue-eyed gene.

Of course, things are a bit more complicated than just dominant/recessive. Another popular middle/high-school genetics example is rose color: red, pink, or white. White is recessive, and red is dominant. There is not a “pink” version of the rose-color gene; pink only arises when the rose has one dominant copy and one recessive copy. Back in high school, I assumed that this was like mixing paints: one gene makes red paint and one gene makes white paint, and then the paints mix together to make pink. That is NOT what happens. There is no “white paint” for roses. White would be a lack of paint (pigment), in this case. White is the color of the blank canvas, of the default rose petals. Pink color occurs when there isn’t enough red pigment to fully saturate that canvas. If both genes are the red version, the petals will be a nice, deep, red color. If only one gene codes for red pigment, the rose can work its butt off, but it will never be able to make enough pigment to make its petals fully red. It’s like trying to paint a room red with only one tablespoon of red paint: you can spread it thin and cover each wall, but it is going to be very, very light.

If you look at a “white” gene copy in roses, you’ll likely find that it looks exactly like the “red” copy…but with a key difference. Again, there are lots of things that key difference might be: a huge portion of the gene could have been deleted, for instance. Or there may just be one single mutation that throws everything into disarray. There’s more than one way to skin a cat, and there’s more than one way to break a gene.

To tie this back in with red-green colorblindness: to see each color, your eyes need to make cones (color receptors). Those cones are made of proteins and, without them, you wouldn’t be able to see color. The proteins those cones are made of are the end-products of genes, like how babies are the product of unprotected sex (straight sex, that is. #LoveIsLove). The “colorblind” version of the red-green color vision gene is just the broken version. Without a working gene, you don’t have proteins, and you don’t have red-green cones.

For more info and exceptions to the above paragraphs, please look into: epistasis, incomplete dominance, continuous traits, cones and rods, and genetic inhibition. 

Explain It Like I’m 5:

To me, the words dominant and recessive are a bit misleading. I always imagined that a dominant gene copy would just grow a pair of hands and sucker-punch the recessive copy into submission. Sadly, that is not the case. In my opinion, “dominant” genes should be called “actually accomplishing something” genes, and “recessive” genes should be “broken” genes. Because that’s often what they are: a version of the gene that’s been damaged, and therefore reverts back to the host’s default, as if the gene had never existed.

Take color in roses for instance. What’s the default color for roses? White. A rose needs a functional “red” gene in order to become red. If it only has two broken copies of that gene, it will remain white like a piece of paper with no writing utensils nearby. That is why we see that the “red” version of the gene is dominant and the “white” version is recessive. In reality, the rose either has a functional red gene or it doesn’t.

Color is an easy example. So is sound. The words “dominant” versus “recessive” are directly analogous to a working piano versus a piano with no strings. Someone in another room will only hear sound coming from the functional piano, because it’s the only one making any noise. It’s not that the functional piano is making a superior song: it’s that it’s making a song at all.

Which brings us back to color blindness. Color blindness is recessive because it is the lack of functional color vision. Color vision comes from a working gene copy, and colorblindness from a broken gene copy.

And here you thought I threw in “broken magnifying glass” by coincidence.

What makes a gene “broken”?

Advanced Explanation:

What broke the gene? Well, many things could have gone wrong, because there are many steps to making a gene’s final product, which is a protein. This is the pathway from gene to protein (warning: jargon ahead):

RNA polymerase binds to the gene and reads the DNA code, RNA polymerase makes mRNA, the mRNA goes through several modifications, the mRNA finds a ribosome, the ribosome binds to and reads the mRNA code, tRNAs gather at the ribosome to follow the mRNA instructions to make a polypeptide chain, the polypeptide folds, the polypeptide joins with another polypeptide to make the protein, the protein gets picked up by various cell machinery and shoved out of the cell, and the protein travels to its end point.

If even one of those things goes wrong, say goodbye to your brown eyes. Or, in our case, to red-green color vision.

But because this series is “Vertical Integration” and not “Vertically Integrate until you get to the gene-to-protein step, and then span out,” we’ll be focusing on the very first step: RNA polymerase binds to the gene. Your genome is filled with both genes and non-coding regions, and RNA polymerase is only supposed to bind to and read genes. So it won’t bind just anywhere, because it wasn’t designed to. But every gene is different. Just like how you would be confused to try and find the gene portions of the genome amidst trillions of As, Ts, Cs, and Gs, RNA polymerase can’t tell a gene from a non-coding regions. Instead, at the beginning of many genes are one (or several) promoters–DNA code that RNA polymerase can find like a homing pigeon finds its home. The more promoters, the stronger the call. These regions are normally really specific: that way, RNA polymerase will bind only to those promoters, and then just start moving sideways to process the gene that follows it.

Again, several things could go wrong. Namely, the promoter could be blocked by something (a long list of possible somethings), or it could just mutate. Again, RNA polymerase is trained to only go to that one sequence, so if some of the letters of that sequence change, RNA polymerase won’t go there. RNA polymerase, like most enzymes, is very literal that way.

For more info and exceptions to the above paragraphs, please look into: non-synonymous mutation, promoters and inhibitors, chromatin folding, enhancers and repressors, non-coding genome regions, DNA transcription, RNA translation, DNA codons and anticodons, green eyes, enzyme specificity, and protein folding. 

Explain It Like I’m 5:

I like comparing genes to cooking recipes: the recipe does not make the cake. Cooks (in this metaphor, enzymes in your body) make cakes (color vision), following the recipe’s instructions. Yes, you, the head cook, are the enzyme RNA polymerase, which starts off the whole process. To make that cake, you and your cooks need to:

1) find the recipe

2) read and understand the recipe

3) go off and do all the steps required to make the cake

Just like many things can go wrong in a kitchen (not enough eggs, broken oven, lazy cook, pesky dogs stealing your ingredients), lots of things can go wrong in making a genetic trait (cake), which is the end-product of a gene (recipe). Especially in step #3. Here, we’re focusing on step #1: finding the recipe. That’s where you, RNA polymerase, come in to get the ball rolling.

Your cookbook, like your genome, is huge. Absolutely huge. Trillions upon trillions of letters are in that cookbook. To find the recipe you want, you need a table of contents. Without that table of contents, you might find the recipe, but you’re more likely to just change your dinner plans and move onto another recipe (gene) that’s easier to find. In this metaphor, something called gene promoters (homing codes for RNA polymerase) are entries in the table of contents, and DNA mutations are typos in words. In a dominant gene, your table of contents was well-proofread, the head cook can easily find the recipe for boysenberry cake (red-green color vision), and thus the cake gets made (the person is not colorblind). In a recessive gene, your table of contents has a typo where the Google autocorrect on the author’s computer changed “boysenberry cake” to “poison hairy cake.” Or even more confusing, perhaps it was changed to: “senberryboy cake.” If you’re browsing through every entry and are a very literal person (as enzymes often are), you are not going to flip to the page for poison hairy cake, and thus your boysenberry cake will not get made.

As a side note, as a small child, I actually thought that it was “Poison Berry Cake” and refused to eat it. When I found out it was really “Boys ‘n Berry Cake,” I was equally reluctant to eat it because I did not want to commit cannibalism.

 

 

This is Part 1 of a long series. We go much deeper down this rabbit hole, but there isn’t space for it in a single blog post. And, once we go beyond the reaches of my field of biology (which we are rapidly approaching), I will need to fact-check my explanations. Stay tuned for Part II!


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