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 secondhandscience@gmail.com 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, Genius.com (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:

Wild type: tame on the outside, tamer on the inside.
“Wild type: tame on the outside, tamer on the inside.”

You would think the term “wild type” would describe the craziest, wackiest, furthest-out-there members of a species. Teen wolves. Mutant carny folk. Donald Trump.

But no.

In genetic terms, “wild type” refers to what you’d find “in the wild”, meaning the usual, most common, textbook examples. The ho-hummers. Been there, seen that.

When biologists describe things as wild type, they’re typically referring to one of two things: genotype or phenotype. The words look and sound nearly the same, but there’s an easy way to keep them straight:

Genotype starts the same way as “gene”, and indeed refers to DNA sequence, where genes live. A wild type genotype is one that matches the sequence most commonly found in the population. So what are you called if you have a different sequence, and your genotype varies from the norm? A mutant.

Not in a bad way, necessarily. But a mutation — either in one of your cells, or in one of your ancestors’ cells which was passed on to you — is how variation gets into genetic sequence, and those variations are tremendously important. Without mutations, we’d all have the same DNA. We’d all be susceptible to the same diseases. We’d have no flexibility as a species to survive. And we’d only have Teenage Ninja Turtles movies. Who the hell would watch those?

(Of course, according to Gattaca, we’d also all look like Jude Law and Uma Thurman. I’m sure there are downsides to that, somehow. I’ll let you know if I think of any.)

Then there’s phenotype, which starts with “phen”, so the easy way to remember that is “it’s not the ‘gene’ one”. Or make up something about “phenomenal”, maybe. Or “phenylalanine”. I don’t know. What am I, your mnemonics coach?

What phenotype refers to is outward appearance or traits. One or more DNA sequence changes (or genotypes) may lead to noticeable physical changes, or phenotypes. In fruit flies, for instance, there’s a gene that controls eye color. Certain genotypic changes, or mutations, in that gene lead to a phenotypic change: instead of beady little red eyes, the flies have beady little white ones.

Not as dramatic a physical change as you get from frappe-ing a fly’s DNA up with Seth Brundle’s, perhaps. But still, a distinctive phenotype — one for wild type, and one for mutants.

In the phenotypic sense, there is no single “wild type”. No one set of characteristics is standard, with offshoots of eye color and skin shade and curliness of hair radiating from it. You can compare variations to each other, but there’s no reference person or animal or bacterium to call ideal.

Likewise, you can come up with a “reference genome” for a species — and people have, for humans and fruit flies and rats and plants and plants and hundreds of other species. But each of these is just an average of the DNA that’s tested. One particular genotypic locus might have a certain sequence in fifty-one percent of the population, so it becomes “wild type”. But everyone else is then a “variant”, and none of us have the same set of millions of variants currently known. We’re all mutants, if you compare our DNA to the human reference genome, though we’re considered wild type in the majority of genomic positions.

Well, most of us are. Not counting Teen Wolf. Or carny folk. Or Trump. The only “wild type” of thing about them is their hair. Their scary mutant hair.

Actual Science:
Science EncyclopediaWild type
University of MiamiWild type vs. mutant traits
The ScientistGM mosquito cuts wild-type numbers
UCSCThe biology of the banana

Image sources: IJMM (wild type vs. mutant sequence), Geek History Lesson (Michael J. Wolf), Junkee (Teenage Wild Type Ninja Turtles), More Than Words (hairpiece with a Trump problem)

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