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:

Junk DNA: there's a whole lotta junk in ALL of our trunks.
“Junk DNA: there’s a whole lotta junk in ALL of our trunks.”

Comparing yourself with other people is tricky. George Carlin famously pointed out that “their stuff is shit, but your shit is stuff“. Which is great, if you’re comparing music collections or wardrobes or childrens’ refrigerator art.

But there’s another thing we have in common with other people: our DNA. And when it comes to genetic material, it turns out everybody’s is mostly junk. Yes, even yours. And George Carlin’s.

(Well, at this point, certainly George Carlin’s. Unless you count half of Kelly Carlin. Which you probably should.)

But don’t feel too bad about your junky genome. “You are what you eat,” as the saying goes — so if you’ve ever shoveled down a McRib or a whole bag of powdered mini donuts down your gullet, then you knew some “junk” was probably in there, somewhere.

The question is… how much? No one is entirely sure.

Regrettable food choices aside, the degree of “junkitude” in a species’ DNA was first measured in a very simple way. Somewhere within that DNA are a number of genes — regions that are transcribed into RNA messages, and then translated into proteins, which perform most every function in living cells.

Different species have different sized genomes, and varying numbers of genes. Back in the ’60s or so, scientists took a hard line concerning “junk DNA”: if it can produce a protein, it’s useful. If not? Junk.

That leaves many species with an awful lot of so-called junk DNA — and it makes humans look like downright hoarders. Using this definition, roughly 98% of our DNA is pointless garbage. Expired Fruitopia coupons. Porky’s Revenge Betamax tapes. Last year’s newspapers. Or really, any newspapers.

But a funny thing happened on the way to our deoxyribonucleic intervention. As scientists dug deeper into how our genomes work, they discovered something interesting. Our non-protein-coding DNA may be “junk” — but that junk DNA… is not.

Not junk, that is. At least, some of it isn’t. Because while genes — actual, protein-producing sequences — only make up about 2% of our DNA, other regions are pretty important, too. Like telomeres, for instance — little fiddly bits of DNA that “cap” chromosomes to protect the squishy ends. Or for that matter, centromeres — repetitive sequences where two halves of each chromosome are held together, and which are critical during cell division.

But it’s not just structural elements hiding in the junk DNA. There’s other stuff in that shit, too. Thousands of regulatory sites, for instance. All those protein-encoding genes are great — but on their own, they’re kind of dumb. If you don’t want intestine genes turned on in your brain, or adrenaline released along with melatonin — and seriously, you do not — then something has to regulate how and when and where and why each gene gets expressed.

That “something” is a bunch of proteins, mostly — but they do their jobs by sitting down on stretches of non-coding DNA to direct traffic. Take away those “junk” DNA regions, and your gene expression suddenly goes all higgledy-piggledy. Congratulations, spring cleaner. You’re a sewer mutant now.

There are other important things happening in our “junk” DNA, but we’re still discovering what all of them are. Maybe 10% of our DNA is actually useful. Or 8.2%, according to one study. Maybe as much as 50%. But probably not more than that; nearly half our DNA is thought to come from transposable elements and integrated viruses, which are generally not so useful.

So Carlin wasn’t wrong, but he didn’t have the whole story. True, our shit is stuff, and their stuff is shit. But underneath, we’re all 50 to 98% junk. Sorta makes you want to mutter the seven words you can never say on television, dunnit?

Image sources: Biotechnology and Society (junk DNA), Amazing Spaces (Carlin, finding a place for his stuff), YouTube (powdered donut face), Daily Beast (sewer muties, wavin’)

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

Knockout mouse: one lab animal that really goes to the mat for science.
“Knockout mouse: one lab animal that really goes to the mat for science.”

The late author Douglas Adams once said a thing about cats:

If you try and take a cat apart to see how it works, the first thing you have on your hands is a nonworking cat.

He was making a point about how living things are extraordinarily complex, even more so than things like alarm clocks and carburetors and the London Bridge — which, while also complex, can in fact be taken apart and reassembled into reasonable working order.

(By people who are not me. I struggle to reassemble a hamburger after I’ve taken the top off to adjust the pickles.)

Note that the esteemed Mr. Adams never said anything about mice.

Since 1989, scientists have been able to produce essentially the non-cat (and mostly un-messy) equivalent of what Douglas Adams described: a mouse that’s been taken apart to see how it works — and then put back together, with one of the pieces missing.

Unlike your average neighborhood mechanic or electrician, however, the missing bits of these mice are left out intentionally, to find out what they do. And before visions of Frankenmice or other murine monstrosities skitter through your head, let’s clarify that we’re talking about “pieces” at the genetic level. Nobody’s hacksawing the ears off your favorite Disney rodent.

Well. Not for science, anyway.

The term for one of these genetically-altered mice is “knockout mouse”, which sounds like someone Jessica Rabbit shares an apartment with. Or some remedial schlub you have to fight in Punchout if you get your ass kicked by Glass Joe.

Happily, it’s neither. The “knockout” part of the name refers to the knockout of a specific gene. To create a knockout mouse, scientists recreate the sequence of a mouse gene in the laboratory — but with a fatal flaw. They alter the gene sequence so that it can’t produce the functional protein it normally would. They then introduce this broken gene into stem cells collected from mice.

Because the mucked-with gene is still nearly the same sequence as the normal version, some of the stem cells will integrate the new copy into the same spot in the genome, via a process called homologous recombination. It’s a rare occurrence — the cell’s DNA has to need repair in just the right place, when the engineered gene copy happens to be handy — but researchers have designed ways to know when it happens, and to retrieve those few cells where the gene has nestled in just right.

Since each cell contains two sets of chromosomes, the engineered stem cells have one “good” copy of the target gene, in addition to the scrambled one they’ve just picked up. Those stem cells get inserted into an early-stage mouse embryo, which is then implanted into a female mouse to grow. If all goes well, the embryo grows into a baby mouse containing cells from both the original embryo and the injected-in cells. This is called a chimera. And if all goes really well, the sex organs on those baby chimeric mice will come from the injected cells, with one wonky copy of the target gene.

From there, it’s just a hop, skip and a few tiny Barry White albums to a knockout mouse. The chimeras with one wonky copy of the gene in their sperm or eggs are bred, and some of their offspring will inherit that wonky gene — along with a normal copy from the other parent. But, cross-breed a few of those single-copy mice together, and eventually you’ll come up with a mouse with a non-functional copy inherited from both parents. That’s a critter where the gene essentially doesn’t exist any more — and that’s a knockout mouse.

There are now thousands of different types of knockout mice, each demonstrating the effects a particular gene has — by its absence. Knock out one gene, and the mice without it become more susceptible to cancer. Knock out another, and they lose their hair. Another, and the mice grow huge and chubby.

Scientists use knockout mice because many of their genes are similar to ours, and often function in the same way. It’s not a perfect model, but “knockout people” are generally frowned upon in the medical community, so it’ll have to do. And knockout mouse models have been used to study everything from aging to arthritis to obesity to cancer, so they’re extremely useful as research tools.

They might also, according to Douglas Adams’ books, be hyper-intelligent pan-dimensional beings who’ve set up the Earth as a grand cosmic experiment. And he was pretty spot-on about the cat thing, so it’s worth mulling over.

Image sources: Science Alert (leptin KO mouse), S M Ong (D.N.A., looking devious), Carton-Online (Mickey, missing something), One Gamer’s Thoughts (Monsieur Joe, mid-taunt)

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

Frameshift mutation: be VERY careful with your threesomes.
“Frameshift mutation: be VERY careful with your threesomes.”

Imagine you’re a Subway “sandwich artist”.

(I know, it’s very depressing. I’m sorry. It’ll only take a minute, and I promise you won’t run into that Jared guy. Because, yikes.)

As a sub Salvador Dali — or if you prefer, po’ boy Picasso, grinder Van Gogh or hero Edward Hopper — you follow three steps to create each “munch-sterpiece”:

  1. Slap down the spongy bread.
  2. Lay in the meatlike substance.
  3. Sprinkle various wilted veggies to taste.

That’s the procedure, one two three, into eternity.

(Or until school’s back in for the fall. Or you get fired for having mayo-balloon fights. As one does.)

But what happens when you get the sandwich dance wrong?

A simple screw-up — substituting the bread with cardboard, for instance — would ruin a single sandwich. (Or not. Possibly no one would notice.) Ditto for getting the steps out of order, slapping your meat on your pickles or some such thing.

But what would really throw things into a state of hoagie higgledy-piggledy would be to skip a step (or add an extra), without changing the overall pattern. If you had bread and meat ready, for instance, and momentarily forgot that vegetables existed.

(Hey, this is America. It happens.)

You’d know there’s a third step to the sandwich, so maybe you’d move on to bread and create a bread-meat-bread order. But now you’ve already done the bread step, so even if you remember the veggies — hello, lettuce! — your process is out of sync. Your next sandwich would be meat-veggies-bread, and so would the other subs after it, until you found a way to make an adjustment. Or until the manager fired you, because you’re making sandwiches like a crazy person.

What you’ve just done — apart from the important public service of encouraging people to eat somewhere better than Subway — is called a frameshift. When it happens in a sandwich shop, it gets a little messy. When it happens in your DNA, it’s called a frameshift mutation, and it can be very, very bad.

That’s because of the way that information in DNA gets used to code for proteins, which do most of the important jobs around our cells. Most of the genes in our DNA code for proteins, but the DNA information goes through another form called RNA to make it happen. The RNA gets created directly from the DNA, “word-for-word” as it were. So if a frameshift mutation occurs in the DNA — one missing bit of information, or one extra — it doesn’t make much difference here. The RNA is just a little longer or shorter than it ought to be.

Making RNA into proteins is trickier, though. Here, three bits of RNA information code for individual amino acids, the building blocks of proteins. And just like with the blimpie Botticellis above, if a triad stutters out of frame, everything afterward goes to hell. The wrong protein gets built, shorter or longer and unable to function the way it’s supposed to. It’s basically a Franken-protein, and all because of one little frameshift mutation.

While frameshift mutations are relatively rare, they can have huge consequences thanks to the complete horking-up of proteins they cause. Frameshift mutations can cause conditions ranging from Tay-Sachs disease to Crohn’s disease to cystic fibrosis to cancer, and more. Any of which are significantly worse than not getting lettuce on your footlong Italian.

You can reduce your risk of developing frameshift mutations by staying away from suspected DNA mutagens. Cigarette smoke. Ultraviolet radiation. Possibly, Subway food. So keep those DNA frames in sync and if you forget the veggies, then for heavens sake, start over. Sandwich safety first, kids.

Actual Science:
Penn State University / MicrobiologyFrameshift mutations
San Diego State University / Stanley MaloyFrame-shift mutations
Study.comEffects of frameshift mutations: definitions and examples
Baylor College of MedicineLooking for a shift could provide molecular diagnosis in rare disease
GenomeWebExome sequencing uncovers new monogenic form of obesity

Image sources: Slideplayer / From DNA to Protein (frameshift mutation), The Commercial Curmudgeon (Subway sista), Domestic Geeks (frameshifted sandwich), RedBubble (“the only good way this ends” shirt)

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