My research part 1: MicroRNA

My research studies a molecule called microRNA. Don’t feel bad if you’ve never heard of it, since microRNA is a fairly new discovery. The first microRNA was discovered in 1993, and the second one wasn’t discovered until 2000. We’ve discovered thousands of microRNAs by now, but they’re still not something all biologists are familiar with, let alone non-biologists. I know when my advisor initially suggested I study microRNAs, the first thing I had to do was go read the Wikipedia article. I knew nothing!

So what the heck is a microRNA? As the name implies, it’s a very short RNA found in plants and animals. Its function is a little more complicated, so let’s back up a bit. Most people have heard of the “Central Dogma” from their high school biology courses: DNA is transcribed into messenger RNA, which is then made into protein.

DNA serves as the “blueprint” for how to make an organism.The messenger RNA, which as the name suggests, serves as an intermediate messenger between the blueprints in the nucleus of a cell and the machinery out in the cyotplasm. Once in the cytoplasm, the messenger RNA is read by a ribosome, which produces a protein based on the instructions originally encoded by the DNA.

Messenger RNA can be made in varying quantities, and more messenger RNA leads to more proteins being made. The amount of proteins made is just as important as the type of protein being made. Genes are “off” if no protein is produced, and varying quantities of a protein can have profound effects on how an organism functions. This is why large chromosomal duplications are generally lethal or have major effects (like Down Syndrome) – with an extra chromosome contributing to protein production, protein levels are totally out of whack.

But the Central Dogma isn’t so dogmatic. This is where microRNA comes in. In animals, micoRNA functions as part of a protein complex called the RNA-induced Silencing Complex (RiSC). MicroRNA guides RiSC to a particular messenger RNA through complementary basepairing – the A in microRNA matches with a U in messenger RNA, the G with a C, etc. RiSC will then block from becoming a protein. RiSC can do this by directly degrading the messenger RNA, de-adenylating the messenger RNA’s poly-A tail to lead to degradation, or by recruiting other proteins to get in the way of translation into a protein. So when microRNA targets a messenger RNA, it results in that messenger RNA producing fewer proteins than usual. If enough microRNA is made, it may turn the gene off completely.

MicroRNA is especially important because one microRNA can have dozens to hundreds of messenger RNA targets. This means a single type of microRNA can have really profound effects on an organism. It’s one of the most important regulators of gene expression, and is involved in key biological processes like the differentiation of stem cells into specialized adult cells, cell proliferation, metabolism, and apoptosis (programmed cell death). Because it’s so important, most microRNAs are highly conserved across animals. This is also why microRNA has been heavily implicated in cancer – one small tweak can have drastic effects.

Stay tuned for more riveting information about microRNA evolution later!

This is post 6 of 49 of Blogathon. Donate to the Secular Student Alliance here.

The fear of getting scooped & the lack of communication within science

The fear of getting scooped really points to a larger issue within academia. Science is based upon the ability to test hypotheses and falsify data, which is why the open sharing of knowledge is so important. But fears about getting scooped lead to less open communication about methods and results. You don’t want to blab your results to any random person, or reveal too much preliminary data during a talk at a conference. You run the risk of someone running off with that idea and getting it done before you.

And because everyone holds their cards close to their chest, you often don’t know who’s working on similar research. Frequently the motivation to publish is the fear of getting scooped by a research group you didn’t expect. When new scientific papers are published, I always read through the titles in the Table of Content with some trepidation, hoping no one hits too close to my project. That would mean having to shift or completely revamp the focus of your research, which is one of the causes of people staying in grad school longer than expected.

It’s getting to the point where sometimes even published results aren’t immediately accessable to other scientists. Newly published genomes are often embargoed for a year so the lab that produced the data has more time to mine it. There’s a lot of debate over whether this is acceptable. On one hand, the lab in question often spent a lot of time, money, and effort sequencing that genome, and it seems unfair for someone else to swoop in and pick off the low hanging fruit questions. On the other hand, having that genome available is incredibly important so other scientists can judge its quality in order to more accurately interpret the results of a published paper, or to use it in their own research. What good is it to come up with all this knowledge about the universe if no one else is allowed to know about it?

I don’t have a solution for this problem with academic culture, but it’s something that gets brought up a lot. How do you feel about embargoes on genomes and other scientific information? For those of you who do research, have you had problems getting scooped?

This is post 4 of 49 of Blogathon. Donate to the Secular Student Alliance here.

You’re invited: Genomics of Non-model Organisms

I’m on the student/postdoc-lead organizing committee for the following symposium. If the topic sounds appealing and you’re near Seattle, come check it out! As a warning, the talks won’t be tailored for a totally layman audience, but if you have some biology background or just passionate interest, it should be really great!

2012 Genome Training Grant Symposium:
“The Genomics of Non-Model Organisms”
Monday, June 11, 2012

1:00PM to 5:15PM
South Foege Auditorium (S060) on the University of Washington’s Seattle Campus
No registration or fee

Schedule and speakers:

  • 1:00-2:00PM: panel discussion with our speakers
  • 2:00-3:00PM: Cheryl Hayashi (University of California, Riverside)
    Molecular characterization and evolution of spider silk proteins
  • 3:00-3:15PM: break w/ coffee and snacks
  • 3:15-4:15PM: Katie Peichel (Fred Hutchinson Cancer Research Center)
    Genetics of adaptation, reproductive isolation, and speciation in stickleback fishes
  • 4:15-5:15PM: Jay Storz (University of Nebraska-Lincoln)
    Natural variation and genomic architecture of high altitude physiological adaptation in birds and mammals

If you know anyone who may be interested, please invite them! We want a great crowd for our speakers.

Want to learn more about the future of genomics?

My department is hosting a panel on “The Future of Genome Sciences” that is free and open to the public. Here are the details:

Panel Discussion: The Future of Genome Sciences
Monday, May 7th
7:00 pm, Kane Hall EDIT: 120
University of Washington
Seattle, WA
free, no registration required

The speakers will be:

Dr. Bruce Alberts who President Obama has appointed as one of his first Science Envoys.  Dr. Alberts is editor of Sciencemagazine, author of The Cell, and former President of the National Academy of Sciences.

Dr. Natalie Angier who is a science writer for The New York Times and the Andrew D. White Professor-at-Large at Cornell University.  In 1991 she received the Pulitzer Prize for Beat Reporting.

Dr. James Evans who is the Bryson Distinguished Professor of Genetics and Medicine at University of North Carolina and directs the Clinical Cancer Genetics Services at UNC.

Dr. Keith Yamamoto who is Vice Chancellor for Research, Executive Vice Dean of the School of Medicine, and Professor of Cellular and Molecular Pharmacology at the University of California, San Francisco.

The moderator is Dr. Maynard Olson, who is a Professor in the Departments of Genome Sciences and Medicine at the University of Washington and is one of the founders of the Human Genome Project.

If you’re near Seattle, I hope I’ll see you there!

The genetic “proof” for ancient aliens

I have a new, horrible obsession – the History Channel’s show Ancient Aliens.

On Saturday I found myself drinking with a group of my boyfriend Sean’s friends, when one of them announced that we must play an Ancient Aliens drinking game. I had no idea what the show was, but became intrigued when they started discussing the rules of when to take a drink:

  • Whenever someone being interviewed has no relevant credentials like a PhD
  • Whenever someone says the phrase “Some scientists say”
  • Whenever someone says the phrase “ancient astronaut theorists”
  • Whenever an ancient manuscript is displayed
  • Whenever there’s a terrible CGI reenactment
  • Whenever Giorgio starts talking

Me: Who’s Giorgio?
Them: Oh, you’ll know who Giorgio is soon enough.

This is Giorgio, by the way:

…That’s all I’m going to say.

They decided to reduce the list so we would wouldn’t get alcohol poisoning. But I found myself following my own rule of “drink whenever someone says something that blatantly defies logic or is a total non sequitur.” Which meant I was pretty much constantly drinking for an hour and a half. Especially when you’re jumping from pyramids, dragon drawings, Tesla coils, and the Bible all being proof of aliens (just to name a few).

For those of you who’ve never seen the show…I’m not quite sure how to summarize it. The footage looks professionally done since it’s on the History Channel, and some of the shots of the ancient artifacts are cool to see. But if I had to summarize the major theme, it would either be “Brown people never could have done <insert amazing feat here> because they were too lazy and/or stupid, therefore aliens had to help them.” I think my favorite mindblowing moment was when Giorgio explained that:

  • People worship “Gods”
  • But people only believe in things they have evidence for
  • They had written/drawn evidence for these “Gods”
  • Written/drawn evidence is always realistic and never abstract, imaginative, or metaphorical
  • But “Gods” don’t actually exist
  • Therefore they were actually aliens

Oh, Giorgio. How I wish point #2 was true.

Something about the show hooked me in its terribleness. My emotional reaction was actually very similar to the time when I visited the Creation Museum. Yes, I was mad at how they were twisting science, using terrible logic, and spreading blatant lies. But the absurdity of it all was oddly amusing. By the end you find yourself playing along, like you’re watching a fantasy novel… and not something people actually believe.

Also, being heavily inebriated helps.

So Sean and I plowed forward to episode two, since the first two seasons are conveniently available on Netflix. Our “game” was to guess what sort of bizzaro conspiracy theory the show would provide to explain a phenomena they were hyping before the show made the reveal. Sean was a little too excited when he correctly guessed the “Humans and aliens had sex and interbred” plotline. To which I replied, “But they’re an alien. Humans can’t even breed with chimps. Humans would have to actually be aliens seeded here or something for interbreeding to be possible.”

And then that’s exactly what the show said, and I nearly peed my pants laughing.

But the real kicker came when the show brought up the human genome. Sean and I both study genomics and evolution, so we exchanged a wary look. I’ll let you see it for yourself. The clip begins at 7:34 in the first video, and continues until 3:03 in the next.

In case you can’t watch the video or had trouble following that pristine argument, let me summarize:

  • Geneticists discovered the gene HAR1, which is unique to humans and plays a critical role in the development of the human brain.
  • Did it develop through evolution? Francis Crick says human genes couldn’t have evolved because there’s not enough time for DNA to evolve by accident. He said it would be as improbable as a hurricane going through a junkyard making a Boeing 747.
  • Since it couldn’t have evolved, the aliens performed a targeted mutation in HAR1 to make us “human.”
  • We only understand 5% of the genome. If you wanted to record an eternal message that could be decoded by a creature that eventually evolved enough intelligence to decode it, you shouldn’t put it in a monument or text that can be destroyed…put it in the DNA! OMFG THAT’S WHAT JUNK DNA IS! SECRET MESSAGES!

And now, for a quick debunking:

  • HAR1 is present in all mammals and birds, not just humans. But in all non-human species, the sequence is effectively the same, or conserved. The human copy in particular has a number of differences compared to other species, so we consider the human copy of HAR1 divergent. This is not at all the only human gene to be divergent. And all species have uniquely divergent genes – that’s precisely what makes things different species. But no one is arguing that marmosets or fig trees or syphilis are actually aliens with special alien genes inserted into them. Well, maybe people are arguing that. There’s four seasons of this crap, and I’m only on episode 3 of season one. Maybe the syphilis aliens are right after the episode titled Aliens and the Third Reich (I shit you not).
  • Francis Crick has always been a strong supporter of evolution and has spoken passionately about how evolution shaped his scientific investigation. He was one of the Noble laureates who advised US courts bogged down by creationists that “Creation-science’ simply has no place in the public-school science classroom.” He also was an advocate for making Darwin Day a British national holiday. While he was initially doubtful of the origin of the genetic code and wondered if panspermia could be the answer, he later published a retrospective article where he and his colleague “noted that they had been overly pessimistic about the chances of abiogenesis on Earth when they had assumed that some kind of self-replicating protein system was the molecular origin of life.” So, um, no.
  • Francis Crick did not come up with that 747 argument – Fred Hoyle did. That’s why it’s called Hoyle’s fallacy. It’s already debunked a bajillion times by biologists – Dawkins wrote two books about it – so I won’t waste time trouncing it here.
  • Whatever alien thought junk DNA would be a great place for an eternal message is a dumbass. Because junk DNA doesn’t code for a protein or have some sort of regulatory role, it’s what geneticists refer to as “neutrally evolving.” It means it’s at liberty to gather mutations because they don’t have any major effect that would weed them out via natural selection. This is especially true when the show’s premise is that the message was placed there eons ago, and had tons of time to accumulate changes. It also doesn’t explain why chimps share a lot of junk DNA with us, or why a huge proportion of junk DNA are remnants of ancient viruses. I’m sure Giorgio would say that those aliens were trying to throw us off the scent by making it seem like our genomes had evolved through natural processes.
  • They never address the fact that the hypotheses they present throughout the show aren’t even internally consistent. At one point they say all life on earth was put there by aliens, and it evolved naturally. Then they say we ARE the aliens. So what, were the aliens unicellular organisms? How can we interbreed – like they say we do – if we’re that distantly related?! But then they say the proof that we’re aliens is that we look like the aliens…so how about those billions of years of evolution?

In poking around the internet about this show, I discovered that Giorgio had a twitter account, which included this gem:

Lizard people? Total nonsense. Aliens? Of course, duhhhhh.

Oh, History Channel. How the mighty have fallen. I remember when I was little and I’d watch you with my history-buff dad, and learn all sorts of cool things about Egypt and Rome and WWII. But now I watch you to point and laugh.

Scientific publication title of the day

Desperately Seeking Stable 50-Year-Old Landscapes with Patches and Long, Wide Corridors” in PLoS Biology.

I’m not sure if the authors purposefully came up with a title reminiscent of a personal ad, or if it’s just my overactive imagination. Either way, it makes me giggle. I mean, “long, wide corridors”? What a size queen.

For anyone wondering what the paper is actually about, the authors are looking for particular types of environments in order to investigate if corridors effectively conserve biodiversity. Human urbanization (roads, housing developments, Walmarts) serves as barriers that plants and animals have a hard time crossing. This fragments large populations into a lot of smaller ones that can’t interbreed as much. Small populations are more susceptible to events that reduce genetic diversity, like inbreeding and genetic drift. Decreasing genetic diversity is generally considered Bad, because…well, I’m lazy and Wikipedia does a good job at explaining:

“Genetic diversity serves as a way for populations to adapt to changing environments. With more variation, it is more likely that some individuals in a population will possess variations of alleles that are suited for the environment. Those individuals are more likely to survive to produce offspring bearing that allele. The population will continue for more generations because of the success of these individuals.”

Corridors are often used to attempt to make up for this fragmentation, and the authors want to see if the corridors are actually successful in promoting gene flow between populations. Thus their personal ad that made me giggle.


I was playing Cranium with my family, and as luck would have it, my team got an evolutionary question. My dad and grandma turned to me, since, you know, I’m an evolutionary biologist and stuff. This was the question:

“True or False: Dogs are more closely related to cats than they are to bears.”

I knew it was false. I don’t have an evolutionary tree of every species in my head, but I had heard of this comparison before. People intuitively think dogs and cats are more closely related because they’ve both been domesticated – but that has nothing to do with evolution. I also knew this was an example of an evolutionary tree that had been tweaked as we gained more knowledge. Very preliminary, simple genetic studies shows dogs more closely related to cats. But as we expanded the comparison to the whole genome, we found that dogs were more related to bears.

I was very annoyed when I flipped the card to find this answer:

“True – The three species are all distantly related, but genetic evidence has established that bears split off from a common ancestor well before cats and dogs had their big split.”

My family immediately started giggling. “Good job, Miss PhD.” This would not stand. I flipped out the iPhone and searched for a modern phylogenetic tree of carnivores. I immediately found one in Nature Reviews Genetics based on karyotype data, indeed showing that dogs were more closely related to bears than cats.

I pointed at the image on my screen.

“Too bad” my family said, as they continued on with the next question.

It may no longer matter for the game (though my team did win – neener neener), but in case you’re interested… yes, dogs are more closely related to bears than cats. They’re all carnivores. Dogs and bears both belong to the suborder Caniformia, while cats are in suborder Feliformia.

So why was Cranium wrong, if it’s claiming its answer is based on genetic information? The answer lies in the date. I checked the box, and this edition of Cranium was made in 1998. In the rapidly expanding field of evolutionary genetics, that’s ancient. We can now compare whole genomes, while before we were limited to a single gene (at best). Different parts of the genome can evolve at different rates if they’re under selection (or not), so it’s important to look at the big picture instead of a tiny snippet. Our methods and technologies are improving, so our results get more and more accurate.

Hooray for science!

My Skepticon talk: Skeptical Genetics

My talk from Skepticon is now online! If you ever wanted a quick and dirty summary of basic genetic concepts, now’s your chance. I try to address a lot of common misconceptions about genetics and address some of the shoddy ways genetics is portrayed by the media:

That was my first time giving that talk. From the Q&A and questions I got afterward, I certainly know what sort of stuff I need to add, subtract, or explain better. If there’s still anything you don’t quite get about genetics, feel free to leave a question in a comments.

This gives a whole new meaning to high-throughput sequencing

The marijuana genome has been sequenced by researchers at the University of Toronto and University of Saskatchewan.

It’s actually a pretty neat study. They compared two strains of Cannabis sativa: Purple Kush (a “potent” strain used for getting high) and Finola (a hemp cultivar). From looking at the genome alone, researchers weren’t really able to find any striking differences. But then they turned to the transcriptome.

What the hell is that? Time for a quick flashback to high school biology! DNA is transcribed into messenger RNA. That mRNA leaves the nucleus and heads out into the cytoplasm, where ribosomes use it as a set of instructions on how to make protein. A “transcriptome” is all of the mRNA produced by an organism. And yes, it differs from a genome – some genes are highly expressed and produce lots of mRNA, others can be completely turned off, and many are somewhere in the middle. The quantity of mRNA is something marked in the transcriptome.

By looking at the transcriptome, they were able to find that Purple Kush exclusively expresses the gene involved in the production of THC, the psychoactive component of marijuana. The hemp strain, on the other hand, didn’t express this gene at all, despite having it in the genome.

You can check out a draft of the paper at Genome Biology, and even search through the marijuana genome here.

I think the most entertaining part is looking at all of the bad puns journalists are putting in titles. Though I have to take offense at Science’s introduction on their blog post:

Attendees at Burning Man, the famously free-wheeling yearly Nevada art gathering, don’t usually take note of new genomic sequences, but they may want to check out a paper published today in Genome Biology.

Maybe this is just because I’m in Seattle, but I’m pretty sure I’m in the minority in my field because I never tried pot. How dare they imply that stoners aren’t interested in genomics when they’re the ones sequencing the genomes. Especially when Francis Crick admitted to experimenting with LSD when he discovered the structure of DNA. Our field is apparently inspired by psychoactive drugs.

A new religious type of RNA discovered?

The backstory, from reader Arctic Ape, a Finnish graduate student:

Adjacent pic is from a whiteboard in a student clubroom at the University of Helsinki, Faculty of Agriculture and Forestry (or, as we call it, “Wood & Weed Science”). Someone had drawn a crude chart of plant floral induction pathway and another(?) person had made some additions, including labeling “mRNA” as “missionary RNA”. I thought your readers might want to explain in comments what exactly is “missionary RNA” :)

Missionary RNA…I wonder what it does? Maybe this is the mechanism behind gene conversion *ba dum ching* (For the non-biologists, the correct label is “messenger RNA”)

I loved Arctic Ape’s PS:

(By the way, almost all our student clubs are curriculum-related, but we’re still mostly not huge nerds. For example, the rest of the whiteboard featured a poop joke in Finnish.)

Poop jokes: A universal staple in graduate student humor.

This is post 21 of 49 of Blogathon. Pledge a donation to the Secular Student Alliance here.

An intro to the neutral theory of evolution

From a top donor:

“I’d like you to write a blog entry (primer) about neutral theory aimed at the layperson.”

Okay, I’m not going to lie. I’ve been secretly hoping someone would bump this question out of the top ten, mainly because neutral theory is kind of boring and vaguely confusing and hard enough to explain while using biology buzzwords. It’s even harder to explain when you only have 30 minutes to write about it and it’s supposed to be targeting non-biologists. When I shared this question with some fellow genetics grad students, the general response was “Ewwwww.”

But I will try my best!

When most people think about evolution, they think of adaptations. Something in the environment puts selective pressure on a certain trait, and organisms with that trait are more “fit” (reproduce more). For example, rabbits that live in snowy climates are more likely to survive (and reproduce) if they have white fur that helps them blend into the snow. If a mutation randomly arises that make their fur white, or just lighter, that rabbit has an advantage over the other rabbits – the dark brown ones are going to be the first ones that are eaten.

There are lots of examples of adaptive evolution through natural selection, and people know them more because they make good stories. The most famous example of evolution, Darwin’s finches, is a case of adaptive evolution.

But not all evolution takes place because of natural selection. Evolution is at its simplest defined as the change in allele frequencies over time. That’s where neutral theory comes in. Neutral theory states that most evolutionary changes are the result of random drift of neutral mutants.

Buzzwords buzzwords, I know. So let’s take it one step at a time and pretend that we’re looking at a population of unicorns (if we’re pretending, might as well pretend all the way).

Alleles are just two different forms of a gene. Genes are usually hundreds or thousands of basepairs long, but let’s pretend we’re zooming in on three bases in a gene for fur color. If you have the sequence AAA, your fur is white. But if you have AAG, your fur is pink. AAA and AAG are different alleles.

Now let’s say all of the unicorns start as AAA, and then from mutation you get a unicorn who’s AAG. Being pink has no effect on the unicorn. He’s not more likely to get eaten, he doesn’t live longer, he doesn’t have more luck with lady unicorns. It’s a “neutral” mutation because it doesn’t change the unicorn’s fitness.

That’s where random drift comes in. Drift simply refers to the frequency of one allele changing due to random chance. That is, nothing is selecting for pinkness. Maybe that unicorn just happened to have more offspring. Maybe the population underwent a bottleneck and was reduced to just a few unicorns, the pink one happened to survive, and now his pinkness will make up a larger percentage of the population. Maybe a couple of unicorns, including the pink one, happened to get isolated on one side of a river, so that side eventually had a lot of pink unicorns, while the other has a lot of white ones. Through random chance alone, a neutral mutation can grow to high frequency or even reach 100% (what biologists call “becoming fixed in a population.”)

When you get into the mathematics, you assume that random neutral mutations occur at the same rates across individuals. This is how biologists get things like “molecular clocks” where they can tell when two species diverged from each other.

…And I have no idea if that made any sense, but I’m out of time. You have all now been exposed to (a shoddy summary of) evolutionary theory, congratulations. If anyone would like to explain further or correct me in the comments, please do so!
This is post 20 of 49 of Blogathon. Pledge a donation to the Secular Student Alliance here.

Neanderthals and the beauty of science

A common creationist debating tactic is to sneer at science, saying something like “It changes all of the time! Scientists can never make up their mind, and often times they’re wrong! Why would you want to trust something that admits it could be wrong?”
And my response is usually to laugh, because that’s precisely what makes science so wonderful. We don’t stick with some dogmatic book even when faced with mountains of contrary evidence. We’re constantly trying to figure out where we’re wrong, so we inch closer and closer to an understanding of reality that’s based on…well, reality. Finding out we were wrong and correcting that mistake is the beauty of science.

I bring this up because a recent news story illustrates this perfectly to me. You may have seen the story circulating that non-African humans are part Neanderthal. Yes, some Neanderthals and Homo sapiens interbred back in the day!

At first I was a little confused, because I thought we had established this in May of 2010 when the Neanderthal genome paper by Svante Paabo’s group came out. But this new paper serves as a confirmation of that work, since it avoids one of the main criticisms of the study – that the human and Neanderthal DNA were cross contaminating each other. This new research only looked at human DNA, and compared it to the Neanderthal sequence. What they found was that about 9% of the X chromosome has a Neanderthal origin in non-African humans.

But if I go back to just April of 2010, everything was different. I was taking my 500 level Evolution class at Purdue, about to graduate. Our final project included downloading mitochondrial DNA sequences of humans, Neanderthals, and other apes to determine if humans and Neanderthals had interbred. From that data alone, the conclusion was an obvious “no.” And that’s what all prior knowledge had said up until that point.

I remember one of the last questions on the project being to explain how new information could potentially change this viewpoint. We needed the whole genome before we could definitively say Neanderthals and humans didn’t interbreed! Mitochondrial DNA is only a tiny part of the whole genome. We need more information because we’re so closely related. And what if only Neanderthal males were the ones mating with humans? Then no Neanderthal mitochondrial DNA would be passed on at all!

One year later, and my professor has to totally redo his lesson plans.

And that’s what makes science awesome.

This is post 3 of 49 of Blogathon. Pledge a donation to the Secular Student Alliance here.