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:

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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· Categories: Biology
What I’ve Learned:

Viroid: the simplest is as the simplest does.
“Viroid: the simplest is as the simplest does.”

Everyone I know is trying to “simplify”, in any way they can. They’re downsizing their houses. Giving away old clothes. Cutting out cable. (But not Netflix, because come on, Unbreakable Kimmy Schmidt, already.)

Pretty much anything short of donating their kids to science and moving into a zen garden, these people are doing in the name of simplicity. And you know what?

They’re amateurs.

Because how “simple” are you, really, when you’re still human? There are all sorts of complicated things going on inside us — and I’m not just talking about our Facebook relationships or the way we feel about Charlie Kaufman films.

Human bodies are all kinds of intricate. You’ve got circulatory systems and immune cells, respiratory tracts and reproductive organs — and that’s just the tip of the person-berg. “Simplify” all you like, but if you’re holding on to all that bodily baggage — with your fingers; don’t even get me started on fingers — then you’re not very simple at all.

And what’s more, if you think you need all of that — or any of it — to live in the world, grow up and pass on your genetic material, then you’re wrong. You can do all that with less. Much less. If you really want to simplify, take a cue from a viroid.

Viroids are about as small — and simple — as a reproducing bit of schmutz can get. Classified as “sub-viral pathogens”, viroids have almost none of the fiddly biological bits even most tiny organisms hold dear. Take amoebas, for instance; these microscopic little one-celled critters still have tiny tails to move around with, a way to take in nutrients and a nucleus for their genome. Ain’t no viroids got time for that.

Bacteria are even smaller than amoebas, but they at least have a cell membrane, and enzymes and stuff kept handy in pockets, for when they’re needed. Viroids got no enzymes, no pockets, and no cell to keep them in.

Viruses are tinier still, and are mostly just made up of a few genes on a strip of DNA. But at least — at least, for crissakes — they have the decency to cover up their genetic material with a membrane of some kind, and to code for a protein or two.

But viroids? Nuh uh. They’re nothing but naked RNA, single-stranded genetic material all folded in on itself. No membranes, no cell walls, no nothing. They don’t even code for proteins — they’re just themselves, the epitome of “simple”. Viroids are out there. And they’re lovin’ every minute of it.

Of course, living simple has some downsides. So far as we know, no viroids have Twitter accounts, for instance. Also, they can’t reproduce by themselves — we’ve all been there, amirite? — but need to infect a living cell to “borrow” its machinery to make more copies of its RNA. Most of those living cells are in plants; viroids have been identified that infect potatoes, eggplants, avocados and coconuts, among others.

Because they can’t reproduce by themselves — or in ugly-RNA-bumping pairs — viroids aren’t considered to be “alive”, exactly. But they may provide a hint as to how life ultimately began on the planet. Making copies of oneself — with help, and before one really has a “self” to speak of — isn’t much, perhaps. But it’s an important step on the way to truly living, and might have been critical to the formation of the very earliest life forms.

And today, viroids can still float around a farm field, dig into crops and pass along their genetic material to new generations. From what I’ve seen of the “simplify” crowd, most of those people would love the viroid lifestyle. Or near-lifestyle, as the case may be.

Of course, that “lifestyle” also involves running around naked, mooching other peoples’ equipment and using vegetables for sex.

I’m not saying that would deter any of the hippies pining for a life change. But suddenly, viroids don’t sound so “simple” to me.

Also, that Netflix queue of mine isn’t going to watch itself. I’ll pass.

Actual Science:
Virology BlogViroids, infectious agents that encode no proteins
Small Things ConsideredSmallest Things Considered
New York TimesA tiny emissary from the ancient past
Science Magazine / OriginsFast-mutating viroids hold clues to early life
Washington State UniversityHop stunt viroid research

Image sources: Nature Reviews (viroid structure), Neptune Society (kids with signs), QuickMeme (Kramer, LOVIN’ it!), The Snipe (sexy, sexy eggplant)

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

Splice junctions: snipping ads out of your favorite programs since many millions of years ago.
“Splice junctions: snipping ads out of your favorite programs since many millions of years ago.”

Your DNA is crap.

Well, mostly it’s crap. But so is mine, and so is everyone else’s. For all the wondrous and amazing things our genetic code can accomplish, most of the really good stuff comes from a tiny little fraction of the genome. The rest is poorly understood, variable in quality and dubious in value.

In other words, your DNA is like cable TV.

Think of it this way: imagine all of your genetic material — three billion DNA base pairs tucked into every one of your cells, and responsible for making you “you” and not me or a goldfish or a head of iceberg lettuce — laid out in a line, like a TV program schedule. The “shows” are the genes — twenty to thirty thousand snippets of code that actually mean something. These can be read to produce proteins, which do just about all of the important work in your body, from grabbing the oxygen you breathe to growing toenails to helping you decide how much of that Buffy the Vampire Slayer marathon to sit through.

(All of it. Duh.)

But what’s between those shows you like, in the great abyss of “five hundred channels and nothing on”? Well, a couple of things. First, there are “pseudogenes” — stretches of DNA that look like they might do something interesting, but which have been mutated and mangled past the point of being useful. These are your knockoff shows and half-assed sequels: Who Wants to Be a Thousandaire?. Seinfarb. Home Alone 9: The Alonening. No good can come from these, clearly.

There are other bits of fluff, too. Near-endless repeats — possibly important in DNA for structure; used in TV as an excuse for USA to cram another NCIS rerun on the schedule. And long, droning stretches of apparently random sequence — the overnight informercials of the human genome.

But back to the genes. These are structured like TV shows in another important way: our genes contain commercials. In the genome, these are called “introns”, and are bits of DNA in between the important parts (which are called “exons”). When the gene is finally translated into a protein, these bits are snipped out in a process called splicing. And the edges of each intron in the line contain a short code called a splice junction, which tells the translation machinery where to snip the nonsense out.

So if a gene is like a television show, then a spliced gene is like watching with TiVo. Which is clearly better, because you can skip the commercials. And it’s made possible at the genetic level by splice junctions.

These splice junctions are tiny two-base sequences — usually GU (in RNA-speak) on one end, and AG on the other — that mark the intron they surround for snipping. But it’s not always a simple matter of lopping out the “commercials”. Many of our genes undergo a process called alternative splicing, where chunks containing multiple introns (and the exons between them) can be yanked out, producing multiple proteins from the same gene — sometimes with very different functions.

Think of alternative splicing as watching through the setup of, say, your favorite cop drama, then skipping to the end when they catch the perp. All that stuff in the middle is just filler and dusting for fingerprints, right? Much better.

So the next time your body translates a gene into a protein — which is all the time, obviously — give a little thanks to the splicing, and splice junctions, that make it possible, by editing out the crap in your cable lineup of a genome.

And then get back to that Buffython. Season 5 isn’t gonna watch itself, sunshine.

Image sources: Wikipedia (splicing), The Mental Elf (TV watcher), Uncoached and TimeToast (intron-snipping TiVos), Jack of All Trades… (Buffy squeal)

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