Other Genetic Principles

I am curious if there is any evidence that a gene is more likely to be passed on if it is turned on. Also, is an on gene more likely to be affected by mutation?

-A curious adult from Toronto

May 29, 2008

What an interesting pair of related questions! Whether a gene is on or not doesn't really affect its chances for being passed down.

We all have two copies of every gene: one from mom and one from dad. Only one copy is passed on to your kids and that copy is "chosen" pretty much at random. This random selection isn't affected by whether or not a gene is on.

But genes that are turned on are more vulnerable to DNA mutations. Luckily our cells have evolved ways to make up for this. The end result is that genes that are on do not end up with more mutations.

Turning Genes On and Off

Let's step back a moment and talk about how genes are turned on and off. This is a fascinating but complicated topic. A good understanding of how it works should help answer your questions.

As you may know, just about all the cells in our body contain DNA. DNA has genes that are instructions for how to build and run each one of us. The DNA (and so its set of genes) is the same whether it is in a brain or skin cell. This entire set of DNA is called a genome.

But wait a minute! If DNA is the instructions, and each cell has the same DNA, wouldn't all cells end up being the same? How can we get different types of cells to do different things? Obviously our brain works very differently from our skin.

Well, it turns out that there is a very complex system of turning different genes on and off. Brain cells know to turn all the "brain genes" on and all the "skin genes" off. By turning on or off the right set of genes, you can get all sorts of different kind of cells, even when they all have the same DNA.

This turning on and off of genes is called "gene expression." Genes that are turned on are said to be "expressed."

I think it's worth mentioning here that having a gene expressed isn't necessarily an advantage. Ok sure, you definitely want to turn on brain genes in a brain. But you really don't want to turn on those brain genes in a skin cell.

Sometimes when a gene is turned on in the wrong place it is a disadvantage. For example, cancer is often caused by genes that are on when they shouldn't be. Both turning on and turning off genes at the right place and at the right time is very important.

So let's think about what happens when it comes to passing your DNA on to the next generation.

When we have kids, a special type of cells called germ cells is involved. These are more commonly known as sperm and egg. It is the DNA in these germ cells that's going to be passed on.

Germ cells carry just one copy of all their genes instead of two copies like most of the other cells. That way when the egg and the sperm fuse, the child gets two copies. But aside from that, germ cells carry the exact same DNA as the rest of your body. And the genes that are expressed in a germ cell are different than the ones that are expressed in the brain or skin.

The sperm or the egg doesn't really care (or know) what genes were turned on in the brain or skin cells. All the genes in these germ cells are going to get passed down and inherited by the child! This is why gene expression doesn't impact heritability. But it can affect how vulnerable DNA is to mutations.

Gene Expression Does Not Result in More Mutations

At first I was puzzled by the second part of your question. Why should expressing a gene make it more susceptible to mutations? Once I started to think in more detail about how DNA works, I realized that expressed genes would be expected to build up more mutations. But they don't.

To understand all of this, we need a little better picture of what's going on when genes are turned on or off. We talked earlier about how just about every cell in our body has the whole genome.

The genome carries a lot of information. In fact, if you were to stretch out the DNA from just one cell, it's going to be about 6 feet long! Cells are about 1/1000th of an inch wide. If you just try to cram the DNA in, it's not going to fit very well. It will take up too much space and will be a jumbled mess.

To get around this problem, life figured out a way to compress the DNA into small bundles. Think about your garden hose. If you just leave it in a messy pile, it's going to take up a lot of space. Instead, if you wind it into a neat bundle, it takes up a lot less space. Same thing with DNA. Our cells wind our DNA onto spools so it fits better into the cell.

Now that you have a neatly wound up bundle of DNA, how are you going to get at the part of DNA you need to turn on? Well, you're going to have to unwind and stretch out that part of the DNA. All other parts of the DNA that are turned off are still bundled up.

Exposing DNA to turn on a gene is like leaving a garden hose unwound in my neighborhood. I absolutely adore my neighbor's dog but he loves to chew on anything he can get a hold of. If I keep the hose bundled up, he can't get to it. But if I leave it stretched out and exposed, he's free to come and chew on, gnaw and destroy my hose.

The same thing is true for DNA. Of course, reading a gene doesn't make it more likely that a dog will chew on that gene. But it does make it more likely that something will damage the DNA and cause a mutation.

That something that can damage DNA usually comes from the environment. Things like toxic chemicals or UV light. Imagine you're a small molecule of toxin or UV radiation that likes to damage and mutate DNA. Which part of the DNA will be easier to get at? That's right, the exposed parts.

In other words, when you turn on a gene, you have to unpack that part of the DNA. By unpacking it, you also expose it to all the nasty stuff out there that wants to damage and mutate it. This is why genes that are turned on are more likely to get mutated.

Fortunately for us, this isn't the whole story.

Mutations in genes are usually bad for us. Sometimes, REALLY bad. They can lead to things like cancer. Well the cells aren't going to just sit around and let their genes get damaged. Nature evolved a solution.

This is called DNA repair machinery. Basically it's a molecular machine in our cells that works kind of like the spell check on your computer. It just goes around and makes sure that there aren't mistakes in our DNA code--mistakes caused by mutation.

One special kind of DNA repair machinery is called "Transcription-coupled Repair." Basically it is a repair machinery that checks only the parts of the DNA that were recently turned on. This extra spell checking balances out the effect of increased mutation in these parts of the DNA.

Bottom line, it looks like mutation and repair cancel each other out -- there are no extra mutations just because a gene is on.

Yuya Kobayashi, Stanford University

DNA is compacted like this rubber band so it can all fit into a cell.

Bundled DNA, like a bundled hose, is protected from DNA damage.













UV light is one source of DNA damage.