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!

Z-DNA


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

Z-DNA: Because everybody needs a little time to unwind.
“Z-DNA: Because everybody needs a little time to unwind.”

Maybe you’re familiar with the fundamentals of DNA. A pair of organic biopolymer strands composed of covalently-bonded nucleotide molecules, wrapped together in a double helix. It’s not exactly simple. But the basics are pretty well established, thanks to Watson and Crick (and Franklin, and Gosling, and a bunch of others). If that’s as complicated as it gets, super.

Naturally, it gets more complicated. The universe is a smug little infinitely-large bitch, yo.

One way DNA gets harder is the way that pair of helices wrap around each other. You’d think there’d just be one way to fit, like Legos clicking together. But no. A DNA double helix is more like a jigsaw puzzle: if you get really frustrated and smush the pieces into those little holes, it’ll go together just about any way you want.

In nature — which in this case means, in you — DNA comes in (at least) three forms. The usual, vanilla, run-of-the-mill DNA in most of your cells is called B-DNA. I don’t know what the B stands for, but almost all DNA looks like this, so I’m guessing it’s Boooo-ring.

Moving on to something sexier.

A-DNA is similar to B-DNA structurally; they’re both wound in a “right-handed” orientation, and spoon together like desperate freshmen on a third date. But A-DNA is scrunched up even tighter, like an overwound Slinky. That’s not especially surprising, because you only see this form in DNA that’s dehydrated. I don’t know how your last hangover felt — but twisted up, jumbly and curled in on yourself is probably not a bad description. That’s probably why they call this A(lcohol-soaked-bender)-DNA.

But it gets even weirder.

The third form of naturally-observed DNA is called Z-DNA, and it’s pretty freaky. Like, up is down and right is left and Team Edward and Team Jacob living together in sparkly harmony freaky. First of all, it’s not right-handed. The two strands flip directions and twist the other way around each other, like some genetic freakshow oozing out of Ned Flanders’ Leftorium.

Z-DNA is also ganglier than the other forms, twisting every two base pairs instead of one. It’s not a great look. And the Z stands for “zig-zag”, which is only about a half-step above naming a DNA confirmation “humpback”. Or “pizzaface”.

In the end, you sort of feel sorry for Z-DNA. It looks like some kid accidentally broke a real DNA molecule and tried to rubberband and bubblegum it back together, but there are pieces left over and none of the cracks line up right. It’s the Steve Buscemi of the deoxyribonucleic acid world.

But don’t feel too bad for Z-DNA. Despite it’s lopsided ugly-lefty-ducklingness (or maybe because of it), Z-DNA may actually turn out to be pretty important. Scientists are still exploring its role in biology, but it’s thought that regular old B-DNA can somehow drunken-Twister itself backwards into Z-DNA at spots where transcription occurs in the genome. And since transcription is where the DNA template gets read as RNA, which then becomes the proteins that every cell needs to survive, that’s kind of a big deal. If not for this temporary unwinding into Z-DNA, all our DNA might scrunch up together, winding tighter and tighter like a raging genetic-scale hangover. Even tequila shooters can’t hurt you that bad.

So we should all appreciate our letter-coded DNA double helix friends. B-DNA, steady and boring and essential — the plain white underpants of our genetic material. And A-DNA, which reminds us to hydrate at parties, and also not to get too wound up over things. But especially Z-DNA, the southpaw oddball of the group. Z-DNA demonstrates that even the strangest-looking among us have a role to play, and no matter how weird left-handed people are, we shouldn’t kick them out of the nucleus.

Also, we shouldn’t feed them through a wood chipper, probably. But it is about time to watch Fargo again on Netflix. Thanks, Z-DNA!

Actual Science:
Tulane University – DNA Structure
UCDavis BioWiki – B-form, A-form, Z-form of DNA
UniSci – Left-handed DNA seen to be biologically important
Arizona State University – Virus researchers close in on the secret life of DNA
io9 – Ten things you probably didn’t know about DNA

Image sources: Neuroscience News (“Now I know my A, B, Z…), Nothing Is Going to Last (nailed-in jigsaw piece), Leftorium.com (Leftorium, the store), Dawson Reviews (gimme Buscemi)

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Splice Junctions


· 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.

Actual Science:
Scitable – RNA splicing: introns, exons and spliceosome
CSHL DNA Learning Center – Transcription and translation: RNA splicing
NobelPrize.org – Alternative splicing
BitesizeBio – What is alternative splicing and why is it important?
Brown University – Lariats: how RNA splicing decisions are made

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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Ubiquitin


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

Ubiquitin: It's everywhere you want to be (and several places you don't).
“Ubiquitin: It’s everywhere you want to be (and several places you don’t).”

This is one of those times where you can learn about science by knowing a little English. Like how you figure out the dinosaur brachiosaurus was made out of grandma candy, or that the element proactinium will cure your acne, probably.

Sorry. This time will be better. I promise.

The protein “ubiquitin” was so named, back when it was discovered in the 1970s, because it was ubiquitous — in other words, everywhere. Every tissue scientists studied, every microscope they looked in, ubiquitin was there. Probably with enormous lapels and feathered hair, humming Jim Croce ballads. But it was there. Ubiquitously.

But what is it, exactly? Ubiquitin is a small protein that’s now been found in nearly every eukaryote — that is, most anything more evolved than a bacterium. It’s in most every type of tissue, and its job is to be glommed onto other proteins as a sort of targeted messaging system. Think of ubiquitin as the “Kick Me” sign of the cellular schoolyard.

Basically, it works like this: special proteins produced in our cells latch onto ubiquitin proteins and activate them — like writing the message on the sign. Then the ubiqiutin is hooked onto a different specialized protein in a process called “conjugation”. This gets it ready for the final step, like attaching a piece of tape to the top of the sign.

(Hey, genetics was invented before we had Post-It notes, all right? If you wanted to stick a sign to something back in the old days, attaching the tape was a separate step.

And yes, we walked uphill in the snow to do it, and we liked it. Shaddup.)

The final step, ligation, sticks the ubiquitin to whatever target protein is supposed to receive the message. Sometimes one ubiquitin is slapped on; sometimes, it’s a whole chain, like a bunch of latched-together plastic monkeys. Depending on which, and exactly how they’re hung on, determines exactly what fate lies in store for the poor unsuspecting tagged protein.

The most well-studied kind of ubiquitination (or ubiquitylation, if you’re really going for the Scrabble words, Einstein) involves a chain of ubiquitins strung together in a certain way, then tagged onto a protein. The result? That tagged protein is doomed to destruction. The message here is “Kick Me, Hard“, and the intracellular bullies are happy to comply.

But ubiquitination isn’t always a Mafia-style kiss of death. Some ubiquitin tags lead to a protein’s activation, or to being transported to a different part of the cell. So “Kick Me On”, or “Kick Me Over There”, if you like. It all depends on the message, and how it gets delivered. Uniquitin’s not bad; sometimes it’s just attached that way.

Ubiquitin thus plays a whole set of important roles in cells — keeping materials moving, cleaning up waste and flipping switches throughout a cell’s development. That makes it crucial for survival, and also something for infectious agents (like the flu virus) to try and exploit.

For figuring out the ubiquitin signalling pathway leading to protein degradation, three scientists were awarded the 2004 Nobel Prize in Chemistry. Two of them were from Israel, and the third was a researcher from the United States.

Because of course he was, right? Those guys are everywhere.

Actual Science:
WiseGEEK – What is ubiquitin protein?
Baldwin-Wallace University – The ubiquitin system
YouTube / Scottish Enterprise – Ubiquitin proteasome system programme
Bioscience Technology – Applying proteomics to Parkinson’s
Futurity – How the flu gets cells to crack open its shell

Image sources: Osaka University (ubiquitination diagram), Gold Country Girls (Brach’s old people candy), Dates with Kate (“Kick me”), Calvin’s Canadian Cave of Cool (monkeys, monkeys, monkeys!)

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Gene Drive


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

Gene drives: sometimes CRISPR is the best accessory.
“Gene drives: sometimes CRISPR is the best accessory.”

When you shop for a new outfit, you’re looking for a number of things. It has to fit. It has to look nice. The accessories should match. And ideally, it should be malaria-free.

Genetic scientists don’t shop for clothes much (lab coats never go out of style), but they do struggle with problems like that last one — reducing the impact of diseases around the world. Malaria and others are transmitted via mosquitoes, affecting hundreds of millions of people and killing more than one million worldwide every year. But what if there was a way to genetically alter the blood-sucking little bastards to prevent these infections? And what if it was as easy (relatively speaking, for the lab geek set) as picking out a cute hat to match that kicky new jacket?

Enter the gene drive, which could bring the concept of the extreme makeover to the chromosomes of bugs and pests and maybe even humans all over the world. It works using a system nicknamed CRISPR, which stands for a bunch of long sciency words that no one bothers to remember. The important thing is how it works, which comes below.

(Stick with me here. The beginning doesn’t seem to have much to do with malaria, but it gets better and then all comes together in the end. It’s like the anti-Matrix trilogy.)

Some bacteria have a very clever protein that helps them avoid virus infections. The bacterial cells keep snippets of viral genes around (the structure these are stored in is the thing actually called CRISPR), and this protein — called Cas9 — recognizes the viral sequence as a target, or “guide”. Whenever Cas9 sees this sequence, like when a virus barges in and starts throwing it around the joint, Cas9 cuts it right down the middle and ruins it. No viral genes, no virus, and the bacteria go on to lead long, happy, fulfilling tiny lives. Or not. They’re not really important to the rest of the story, so screw ’em.

The key is, this Cas9 protein doesn’t really care what guide sequence it’s given. So scientists can yank the Cas9 gene out of the bacteria and engineer it into other organisms. Like mosquitoes. They can also engineer in custom guide sequences matching that organism’s DNA — like one for mosquitoes’ immune response to malaria, for instance — and thus effectively delete or mutate just about any gene they like.

With a little extra fiddling — like a perfect scarf that ties the ensemble together — scientists can also use CRISPR and Cas9 to introduce new genes. Better still, those genes can be inserted in particular spots in the genome that have a genetic “competitive advantage”, meaning they get passed on to offspring more readily than most. That means these gene drives could spread through a population faster than the latest French runway fashion. And look damned good doing it.

Gene drives specifically in mosquitoes could be theoretically used in a number of ways. We could make the bugs resistant to malaria and other diseases. We could alter genes that allow insects to pass the disease on. Or we could go all snarky fashion critic on them and wipe them out completely — like skewing their offspring to be nearly all male.

See, “Raining Men” is one thing. But when it rains only men for a few generations, your species got a problem, yo.

The opportunities for gene drives are near-endless. Any species that reproduces sexually — which is most animals, up to and including (most) humans — could theoretically be CRISPR’ed, and convinced to “say yes to the gene”. There are one or two (or thousands) of ethical kinks to work out first, of course. But in terms of the science, we can rebuild those mosquitoes (and nearly everyone else). We have the technology. We can make them less malarial than they were before. Better. Stronger. CRISPRier.

Actual Science:
eLife – Emerging technology: concerning RNA-guided gene drives for the alteration of wild populations
NOVA Next – Genetically engineering almost anything
Scientific American – “Gene drives” and CRISPR could revolutionize ecosystem management
The Scientist – Opinion: on the irreversibility of gene drives
UCLA / John Marshall lab – Gene drive systems for spreading refractory genes

Image sources: Science (mosquito family tree), PRWeb (totally matching accessories), Digital Journal (perfect scarf), Joy Reactor (men, raining [hallelujah])

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Convergent Evolution


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

Convergent evolution: When great genes think alike.
“Convergent evolution: When great genes think alike.”

There’s no commandment in nature saying, “Thou shalt not covet thy neighbor species’ competitive survival advantage.” Mother Nature plays it pretty fast and loose with the rules.

For instance, say you’re a tree frog living high in the branches of some verdant tropical forest. Maybe some of your chittery squirrel pals have adapted their flappy limb skin and learned to glide gracefully from treetop to ground, whereas your species’ method for quick descent ends with a splat and an unfortunate frog-innard mess. Have you missed the gliding boat, simply because you decided to hop off the evolutionary squirrelhood branch before gliding came up?

Not at all, wartyballs. Because you can still develop gliding abilities on your own — completely separate from those showoff squirrels — in a process known as convergent evolution.

As processes go, convergent evolution is really just evolution, in an encore presentation. When the same environmental pressure is applied to different species, they may adapt in ways that appear similar, but are actually unique and occur entirely independently. So just because the tree rats figured out one way to glide doesn’t mean that the frogs can’t find another and glide alongside them. The squirrels don’t hold the patent on the technology; anybody with a flexible genetic code and a few millennia to burn can follow in their footsteps. Even Italian plumbers, apparently. Mother Nature’s not picky.

Are there other examples of evolution going back to the well over and over to solve the same problem in similar ways, like Jonah Lehrer barfing out a thousand words of recycled New Yorker fluff? You betcha.

For starters, there are animal wings. Bats, birds and prehistoric flying dinosaurs don’t have a lot in common — except that they all learned to fly, and grew their own appendages to do so. But in shape and structure, all those wings are different; the adaptations they made were in response to the same need for flight, but unique to the type of animal yearning for air time.

There are plenty of other instances of convergent evolution, too. Like eye structures in vertebrates versus squid, or echolocation in bats and dolphins, or fruit production in a variety of plants. It also happens at the molecular level — some enzymes converge on similar configurations of active site pockets, and some specific DNA and amino acid changes have been found (in the case of sonar-using bats and dolphins) to have occurred in separate species, independently helping to enable the same biological function.

Seriously, that level of convergence is straight-up crazy. Mother Nature goes completely off the rails sometimes. I really think the old girl should switch to decaf.

Actual Science:
University of Texas, Austin – Convergent evolution
University of California Museum of Paleontology – Vertebrate flight: the three solutions to flight
ScienceDaily – Genetic similarities between bats and dolphins discovered
ExtremeTech – Scientists unravel the genetic secrets of caffeine’s evolution in coffee

Image sources: Mr. Kubuske’s blog (wings, wings, wings!), FlippySpoon (Rocky the flying squirrel), The Ultimate Gamer (Mario the flying Italian plumber), Spoonful (crazy-Lee Mother Nature)

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