Note (12/2015): Hi there! I'm taking some time off here to focus on other projects for a bit. As of October 2016, those other projects include a science book series for kids titled Things That Make You Go Yuck! -- available at Barnes and Noble, Amazon and (hopefully) a bookstore near you!

Co-author Jenn Dlugos and I are also doing some extremely ridiculous things over at Drinkstorm Studios, including our award-winning webseries, Magicland.

There are also a full 100 posts right here in the archives, and feel free to drop me a line at with comments, suggestions or wacky cold fusion ideas. Cheers!

· Categories: Biology, Genetics
What I’ve Learned:

Homeobox: when it comes to transcriptional regulation, it's not clowning around.
Homeobox: when it comes to transcriptional regulation, it’s not clowning around.

A lot of my confusion about science isn’t really my fault. For instance, when I was in college, In Living Color was on Sunday nights, and a must-watch every week.

So when I stumbled into genetics class at ass-early Monday morning, I still had Homey D. Clown on the brain. Can I be blamed for thinking “Homey O’Box” was Clown’s Irish cousin? It’s a mistake anyone could make, if they were a fan of sketch comedy. And it was before nine AM. And they weren’t very bright.

Eventually I learned that a homeobox isn’t a clown, but a conserved DNA sequence. With very little variation, you can find the 180-base pair stretch in the genomes of most every eukaryotic species, from single-celled fungi to duck-billed platypi all the way up to humans. Including clowns.

When a homeobox gene is expressed, the 180-base stretch translates into a 60-amino acid structure in the resulting protein. Those amino acids form a three-helix structure, which is just the right shape to hook onto the double-helix structure of DNA. So the proteins containing this structure, called homeodomain proteins, are able to bind directly to DNA, which comes in very handy.

That’s because binding to DNA near a gene is a good start to controlling whether or not that gene gets translated into proteins. Some homeodomain proteins, like those in the Hox family, are “master regulators” of transcription, turning genes on and off like an old-timey switchboard operator. This regulation can be triggered in all sorts of ways, but it’s especially important during early development.

As an example, consider the fruit fly — where the homeobox sequence was first identified, back in the 1980s. Scientists found a bunch of Hox-family homeobox genes in flies, and discovered that when one or more of them were mutated, the flies grew in wild and freaky ways. Scramble one gene, and the flies made four wings instead of two. Hork up another, and they grow mouths on the outside of their face, rather than the inside. And a famous Hox mutation makes flies grow legs on their heads, where the antennae should be.

This may be similar to a mutation I assume Abe Vigoda has, which caused him to grow woolly caterpillars where his eyebrows should have been.

Homeobox genes appear to have been with us for a very long time — since before there was an “us”, in fact. They’re found in organisms as simple as yeast and sea anemones, suggesting that the homeobox sequence first evolved in some ancestor common to all the species where it’s seen today; that ancestor would be around 600 million years old, or way before humans made the party. Or clowns. Hell, even Abe Vigoda might not have been born yet.

There’s also a chance we swiped our homeobox tricks from some ancient pre-dinosaur Cryogenian-era virus. No modern bacteria or simpler species have homeobox genes themselves, but one bacterial virus called lambda phage does have DNA-binding proteins that look an awful lot like homeobox genes. So maybe some prehistoric proto-sponge yoinked this precious and valuable sequence that every animal, plant and fungus relies on today.

Now that sounds like a heist worthy of Homey O’Box. Maybe Homey do play that, after all.

Image sources: StudyBlue, (Homey, not playing that), People in White Coats (antenna-people-pedia), Roscoe Reports (Abe’s bushy brows)

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· Categories: Biology, Genetics
What I’ve Learned:

DNA methylation: it's like a chastity belt for your chromosomes.
“DNA methylation: it’s like a chastity belt for your chromosomes.”

We humans have a lot of genes — twenty or thirty thousand, give or take a chromosome. But we also have a problem. All those genes are packed into the DNA of each and every one of our cells. You’ve got genes for hemoglobin next to genes for neurotransmitters next to liver enzyme genes next to the ones that tell your left foot to grow toenails. The whole caboodle, in every single cell.

You can’t have all those genes turned on at once, in all the cells. It’d be a disaster. Think of your DNA as a big walk-in closet full of clothes. Some things go together, some things clash, and other things you only wear for holidays — or when senile-assed Aunt Clara shows up to see the stupid lop-eared bunny suit she bought you. But you don’t wear everything you own all at once. That would make you a crazy person.

So it goes with your cells. Depending on where they live — in a little row house along the spinal column, maybe, or a brownstone in the colon — they want to fit in with the neighbors and express the right set of genes. When in Rome, do as the Romans. And when in the respiratory system, don’t spew out growth hormones. That’s not your job, bunnybutt.

There are several ways that cells can shut down or “silence” genes, but one of the most common is DNA methylation. It sounds complicated, but it’s actually pretty simple. To make a protein in a cell, a bunch of enzymes have to get at the bit of DNA coding for it. Those enzymes read the code into RNA, and the protein is built from that. “Methylation” means taking a methyl group, a single-carbon molecule similar to methane, and glomming it onto that DNA structure like a wad of used chewing gum.

Slap enough methyl groups onto a stretch of DNA, and those RNA-making enzymes can’t get at it. Any genes in the neighborhood get completely shut down, like a Honda running out of gas or a dudebro wearing Axe cologne. Even better, when the cell divides, the DNA methylation pattern gets passed down the line. So it’s a great way for specialized cells to shut off genes they have no business fiddling with — basically a permanent genetic cock block.

Though critical for development in mammals — pssssst, that’s us — DNA methylation isn’t used in the same way by all species. Fruit flies, for instance, apparently have better things to do with most of their DNA, and yeast haughtily looks down its nose at DNA methylation.

Or would, if yeast had a nose. Or eyes. Or the genes for being haughty.

In other organisms, DNA methylation comes up a lot. Some — humans and tomatoes, for two — use it to silence potentially harmful genes inserted by viruses into the genome. DNA methylation tends to decrease over time, so it can be used as an indicator of aging. And it’s been linked to diseases like cancer, Alzheimer’s and atherosclerosis, and could offer clues about how those conditions develop.

So DNA methylation is pretty important. Without it, all our cells would crap out all the possible human proteins and we’d be big unregulated oozing blobs of cytoplasm. Like a certain amorphously-shaped cartoon character with a distinct lack of impulse control.

And that’s not attractive. I don’t care how cute a bunny suit you slap on it.

Image sources: UIUC TCB Group (DNA methylation), The Berry (Ralphie bunny), GenTwenty (dudebro shutdown), UnderScoopFire! (Homer, unregulated)

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