My research part 2: MicroRNA evolution

Like I said previously, microRNA is typically highly conserved (have the same sequence) across animals because it’s involved in such important biological processes. But some microRNA isn’t conserved, which makes it particularly interesting. Is it not conserved because it just doesn’t have an important function? Is it not conserved because the divergent microRNA confers a specific fitness benefit to an organism? Or is it a rare mutation that leads to a disease like cancer?

That’s where my particular research comes in. I’m investigating microRNA variation within human populations and across the primate lineage. Here are some examples of interesting trends I may find:

  1. A microRNA is totally conserved across primates and other animals. This microRNA is likely involved in a really important biological process, like making a type of tissue.
  2. A microRNA is totally conserved within primates, but differs from other animals. This microRNA could confer some primate-specific trait.
  3. A microRNA is totally conserved within humans, but differs from other primates. This could be an example of “what makes us human.”
  4. A microRNA is not conserved at all. The more likely explanation is that this isn’t a functional microRNA at all. That’s the risk with working with such new data. Other types of small RNA can be erroneously labeled as a microRNA. MicroRNA is a specific class of small RNA because it’s processed in a very distinct manner and has a specific function.
We already know that there are some differences in microRNA between primates. In 2011, Svante Paabo’s group found a number of microRNA that were upregulated (present in higher amounts) in human brain, but not in chimpanzee brain. When they validated which messenger RNA these microRNA were targeting, they found the targets were involved in neural development. This is an exciting possibility for what shaped human brain evolution, but obviously still needs further testing.
The way my research differs is that I’ll be looking at how the sequence of microRNA differs rather than the amount. A sequence difference could totally change which messenger RNA is targeted, which is what ultimately affects the organism. I’ll be experimentally validating the effects of these sequence changes in a number of primates, including humans.

This is post 7 of 49 of Blogathon. Donate to the Secular Student Alliance here.

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.

On blogging about my research

The most frequent topic request I get for my blog is to talk more about my research. Usually the extent I talk about what I do is limited to vague tweets like “Yay, my code actually worked!” and “Why am I in grad school?” But people expect that a blogger who loves talking about science would be gushing about their own research. There’s two reasons I tend to avoid it:

1. Blogging is a a hobby and type of escapism for me. After working all day, I want to do something that doesn’t make me think of work for an hour. But more importantly:

2. Blogging about unpublished research is risky. I don’t want to give away too many details about what I do, because I run the risk that I’ll get “scooped” – that someone else will take the idea and finish it before me. This is even more likely with computational work, especially when using shared or public data. It’s not like I went out an found 1000 samples from rare frogs that no one else has access to – I’m just sitting in front of a computer. Some of the data I use will become publicly accessable by the end of the year, so I’m really pushing to get a paper out quickly. Don’t want to ruin my plan by having a big mouth!

But because you guys ask so persistently, I will blog a little bit about my research today. I’m going to focus mostly on the concepts I’m interested in and previous studies, but hopefully it’ll shed some light on my scientific interests.

This is post 3 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.

Another academic accomplishment!

A new paper that I’m an author on has just been published in DNA and Cell Biology!

It’s a slightly atypical paper, though. When I was a senior undergraduate at Purdue, the Department of Biology staff nominated me to help develop the curriculum of a new NSF-funded, research-based, freshman honors biology laboratory course called CASPiE (Center for Authentic Science Practice in Education). That description is a mouth-full, but it basically means these freshman Biology majors were doing real research for a semester, instead of your typical cookbook lab experiments where the outcome is already known. The class was taught by a professor, a graduate student, and me. I like to say that my main duty was making sure the students plated their bacteria on the correct media and didn’t set themselves on fire*, but I also got to give a lecture on evolution and help out with general concepts throughout the semester.

And now that research has been published in a special undergraduate research edition of the journal DNA and Cell Biology. And it’s atypical because the subject matter is vastly outside of my normal field and interests: Isolation and Preliminary Characterization of Amino Acid Substitution Mutations That Increase the Activity of the Osmoregulated ProP Protein of Salmonella Enterica Serovar Typhimurium. That is going to look bizarrely random on my CV.

But the main congratulations go to the undergrads. They’d be juniors now, and having a paper published by then in a major accomplishment. So kudos to them!

*Though one somehow managed to set the rubber tubing connecting to the gas source on fire. I had a moment of “WTF” and then calmly turned the gas off, and the fire went out. Yay lab classes!

Guest Post: Skeptical dog training

The following is a guest post by Julie Lada, a veterinary student and skeptic who blogs at My DVM Vacation.

Dog training is a hot button issue right now. Dozens of TV, magazine and book personalities are dying to tell you the best way to get your dog to stop jumping up on your guests or going through your trash. In some ways, that is a great thing. Traditionally, dog training consisted of a rolled up newspaper. Getting the issue of dog behavior and training into the public awareness is a huge step for behaviorists and people who are passionate about pet welfare. However, as usual, anytime a topic becomes popular and a profit can be made off of claiming to be an expert, you get bad ideas and bad information being promoted just as heavily as the good. Television shows in particular focus on which host is the most charismatic rather than the most knowledgeable or accurate.

Part of the challenge for me personally, being a vet student and passionate animal behavior geek as well as a skeptic, is the pervasiveness of bad ideas in my field of study. From acupuncture and homeopathy being commonly accepted practices within veterinary medicine to witnessing a colleague perform an “alpha roll” right in front of me, it’s a daily struggle to balance my desire to address these issues with the need to still maintain good relationships and not become known as the token naysayer.

Dog training is one of those topics that must be handled with a delicate touch. A method isn’t purely a method anymore when you’re talking about its application toward an animal that a person feels a strong emotional connection with. The method becomes the person employing it, and its effectiveness becomes intrinsically tied to their value as a pet owner. Like it or not, as any trainer or behaviorist will tell you, the moment you say something like, “Dominance-based training is not as effective as we previously thought and can actually have detrimental effects on an animal” it becomes translated by the person you’re talking to as, “You’re a bad owner and you abuse your dog.”

The problem with any topic in medicine is that bad arguments can be made to sound very persuasive and convincing by using the lingo. The argument behind dominance-based training methods is an excellent example of this (BARF diets are another good example). Advocates such as Cesar Millan point to wolf pack hierarchy models as an example of “natural” applications of dominance-based behavioral conditioning. They tell dog owners to be their dog’s “alpha” by using techniques employed by wolves such as throat holds and alpha rolls. They also attempt to shame owners by telling them that disobedience is a form of dominance which proves that their dog doesn’t respect their status as “pack leader.” The appeal to nature fallacy is something we skeptics are well aware of but it is unfortunately remarkably persuasive with the general public.

A huge, glaring problem with the dominance hierarchy argument is that it makes the assumption that behavior models which we have obtained based on the study of captive wolf packs are reflective of natural behavior in the wild. This is patently false. Firstly, the dominance-based hierarchy suggested by Millan only occurs in captive wolf packs. Wolf packs in the wild consist of genetically related members with the breeding pair being the “alphas.” The frequent displays of aggression and dominance seen in captivity do not occur in a natural setting. Secondly, feral dog “packs” – the aggregates formed by stray dogs – do not display this hierarchy model, so even if it were true of wolves in the wild this model does not appear applicable for domestic canines. (Mech, 1999; Taylor & Francis, 2004)

And then there’s the problem with the word “dominance” itself. Common usage would lead most people to believe that dominance is a personality trait; something a dog just is. A common thing we hear from our clients is, “She’s just so dominant!” Or claim that their dog is trying to be dominant over them. Dominance has a very specific meaning within the context of animal behavior and it isn’t something an animal just is. This is a common misunderstanding and something I’ve even seen my colleagues use. Dr. Sophia Yin, a DVM with a Master’s in animal behavior and a widely renowned expert in dog behavior does a pretty good job of summing it up here. She has written extensively on the topics of dominance, aggression and training and I highly encourage anyone with a dog to spend several hours reading her articles. The American Veterinary Society of Animal Behavior reinforces Dr. Yin’s position with their official statement on dominance theory:

“Dominance is defined as a relationship between individual animals that is established by force/aggression and submission, to determine who has priority access to multiple resources such as food, preferred resting spots, and mates (Bernstein 1981; Drews 1993)… In our relationship with our pets, priority access to resources is not the major concern. The majority of behaviors owners want to modify, such as excessive vocalization, unruly greetings, and failure to come when called, are not related to valued resources and may not even involve aggression. Rather, these behaviors occur because they have been inadvertently rewarded and because alternate appropriate behaviors have not been trained instead.”

But beyond the implausibility of the theory behind the use of dominance and physically aversive stimuli in dog training, as well as the misuse of the term “dominance”, there is the added factor that it just doesn’t have a wide range of practical use. Meaning in the majority of cases, it doesn’t work. Several recent studies have confirmed that dominance/positive punishment training methods have a number of negative effects on dogs (including physical injury and death in cases of choke chains and prong collars being used incorrectly) and can actually impair learning ability. These methods also cause fear and escalate aggression in terms of frequency, magnitude and situational aggression – meaning a dog that wasn’t previously aggressive becomes aggressive, or a conditionally aggressive dog begins to display aggression in situations where it previously did not (Husson et al, 2009; Hiby et al, 2004; AVSAB, 2008). This is particularly worrisome for vets and shelter workers. An owner employing dominance-based techniques toward their dog who is aggressive toward other dogs can actually cause that dog to not only be more aggressive toward other dogs, due to the added negative association with pain and fear, but also cause the dog to redirect its aggression toward its owner. In which case the problem goes from being something that could possibly be solved via proper training to what is a probable euthanasia case.

Positive reinforcement techniques such as clicker training are gaining in momentum, and it’s got behaviorists cheering in the streets (or rather, their offices). These techniques avoid the negative associations with pain and fear seen with dominance-based techniques and thus the ramping-up effect on aggression.

Finally, I know that this is a contentious topic and no doubt the comments will be full of anecdotes from those who have used Cesar Millan’s or other dominance-based techniques successfully. A few words on that.

First of all, there are always outliers. I saw something recently that I quite liked and determined to borrow that said that between 80-90% of smokers will develop lung cancer, which means that 10-20 out of every 100 smokers will not develop lung cancer. So you will often hear claims such as, “My father smoked two packs a day for forty years and died in his sleep at 85 years old!” And while true, it does not disprove the fact that overall smoking is highly associated with lung cancer.

Also consider that the effect of fear on the cessation of all forms of behavior is fairly well documented. Simply put, a fearful animal will stop doing anything, including what you wanted them to stop doing. A dog that is fearful of inviting a painful stimulus can appear to an owner to be “cured” of the unwanted behavior. In fact, the underlying issue of why this dog was exhibiting the unwanted behavior is still unaddressed. A dog that is fear aggressive toward strangers, for example, is still terrified of strangers but simply stops reacting. Don’t confuse this with being a happy, healthy, well-adjusted dog. An animal that has stopping displaying observable fear signals is still fearful, and the use of punishment can contribute to a more unpredictable animal that will give no warning before attacking (AVSAB, 2007)

Just to sum things up on a personal note… A couple of years ago while in undergrad, I was finishing up a meeting with my animal behavior professor and Millan’s name came up. He told me, “You know, every conference I go to, at some point we behavior types get together for drinks and he always comes up. We take turns bashing him over martinis.” So the next time you’re tempted to watch his show or buy one of his books, do so knowing that Millan is the Ray Comfort of the canine behavior world. And dominance theory is the Crocoduck.

Another thing fruit flies and humans have in common

I’m kind of loving this research published in the latest issue of Science, titled “Sexual Deprivation Increases Ethanol Intake in Drosophila.” Science NOW has a good general summary of the paper:

Offer a male fruit fly a choice between food soaked in alcohol and its nonalcoholic equivalent, and his decision will depend on whether he’s mated recently or been rejected by a female. Flies that have been given the cold shoulder are more likely to go for the booze, researchers have found. It’s the first discovery, in fruit flies, of a social interaction that influences future behavior.

Read the rest here.

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.

INJUSTICE

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!