An Interview with Jon Sanders, co-first author on:
Sanders, J.G., Beinart, R.A., Stewart, F.J., Delong, E.F., and Girguis, P.R. 2013. Metatranscriptomics reveal differences in in situ energy and nitrogen metabolism among hydrothermal vent snail symbionts. The ISME Journal, 1-12. doi:10.1038/ismej.2013.45
There once was a pape, and that pape had a hot title: "We Have Never Been Individuals." And in that pape lay a dopely articulated argument. And that argument was that although it has been experimentally and conceptually helpful to pretend that we are all individual organisms, discrete in our genomes and metabolism, this is just simply not true. The very first multicellular organisms evolved into a world that had already been dominated by microbes for like a billion years, and our biologies have always been interpenetratin’. And these symbioses with microbes are not superficial or disposable. These dudes point out that, although It was helpful to ignore (or not know) this fact in the past so that geniuses could figure out how genes work, the time has come to acknowledge that animal-microbe symbioses are “the rule, not the exception.”
Nowhere is the importance of microbial symbiosis more striking that at the deepest darkest bottom of the motherfucking ocean, where the only way that any animals can survive is by givin’-and-gettin’ all night long with the chemosynthetic bacteria that can eat the toxic chemicals spewing out of deep sea vents.
I recently sat down with an American Hero named Jon Sanders and asked him what happened behind the scenes of an incredibly sick pape he recently spewed forth from the depths of Hell. In this pape, Sanders and his co-first author Roxie Beinart invented a new way to collect and sequence fresh RNA from both microbes and animal (snail) at the bottom of the ocean, using an insane and terrifying blender.
1) Describe a day in the life on a boat during a research “cruise.” What’s the Work:Sleep:Insanity ratio?
Close your eyes. Say “I’m on a cruise in the South Pacific.” It’s basically the opposite of that, for two months.
Dominant adjectives for my experience include, “frigid,” “exhausing,” and “loud.” In packing, I foolishly failed to account for the world’s most powerful air conditioning. They keep the inside of the boat at what feels like just above freezing, probably to dry out the air, or maybe to cull the infirm. This led to a frantic search for a sweater when we put in for resupply on the island of Nuku’alofa in Tonga. If you thought that warm clothing would be difficult to find in a place where 50°F is the lowest temperature ever recorded, you would be correct.
Sleep wasn’t much of a consideration. You might get one shot at a research cruise during your PhD, so you try to make the most of it. For the first month at sea, Roxie Beinart (the co-first author of the paper and my partner in crime on this cruise) and I probably slept 2-4 hours a day. We tried to do a preposterous amount of work.
Everything is defined by the ROV’s (ROV stands for Robot Of Vengeance) dive schedule. ROV goes to the bottom of the ocean, ROV comes up with a box of alien deep-sea stuff. The robot’s crew fish it out of the water with incredible crane-ninja skills. Then you need to process that alien stuff, much of which has only been seen by a handful of humans ever in history. Or maybe you’re the first one. I would usually spend 3-5 hours after dives doing dissections. Roxie was running experiments on live animals, which required constant sampling and monitoring. In between, we mostly broke things and then tried to fix them.
I think they still call it a “cruise” (instead of something more descriptive, like “vomit-inducing labor camp”) to lure in naive graduate students like me. I lost 10% of my body weight on that first month. I would do it again tomorrow. I wouldn’t even hesitate.
2) What was the month leading up to the cruise like? What lab equipment did you bring on the boat with you?
Preparation was almost as frantic as the cruise. Roxie and I helped our advisor build a mobile laboratory in a refrigerated shipping container. (In the world of oceanography, these are referred to as “reefer vans.”) We outfit our reefer van with a bunch of stuff to help us replicate the conditions at the bottom of the seafloor. This involves mixing seawater with toxic (hydrogen sulfide) or explosive (hydrogen) gases, then using industrial pumps to force the water at obscene pressures through enormously heavy “aquaria” (basically stainless steel bomb casings). We can use these to run experiments on live animals to help us understand their insane and counterintuitive physiologies.
So for the months before the cruise, we did a lot of plumbing, wiring, and construction. We got crash courses on pump maintenance and operation of mass spectrometers. We organized a lot of various kinds of fittings. Then we packed the van full of crap and sent it on a truck to a train to a ship to Samoa, where we searched frantically for a crane capable of lifting it onto the deck of the research ship.
3) Can you describe, for some of our more thick-headed readers, how there can be a food-chain at the bottom of the sea, where there is zero sunlight to get the primary producers poppin’? Where does the energy come from to fix carbon? Where do the free electrons wind up?
Basically you get life when you take high energy electrons from an electron donor, extract that energy by moving them to a lower energy state in an electron acceptor, and use the liberated energy to self-organize matter in a way that temporarily contravenes God’s obvious thermodynamic will for the universe to become an undifferentiated soup of entropy.
Up here, plants hijack electromagnetic energy from the giant thermonuclear explosion at the center of our solar system to charge up electrons and store them in delicious sugar. We heterotrophic animals do His will by consuming these exquisitely crafted, high-energy carbon rings and turning them into shit, dumping the electrons all the way down the redox scale by splitting oxygen into water.
Under the bottom of the ocean, water in the earth’s crust is heated by the fires of Hell (Editor’s Note: this has been fact-checked). This performs a job somewhat analogous to sunlight by charging up electrons and producing reduced chemicals like hydrogen and hydrogen sulfide. Different microbes pass those electrons down a long chain of different electron acceptors to get energy for fixing carbon, eventually culminating in oxygen from the deep bottom water. (Note that this oxygen is largely a product of photosynthesis, so much of vent life is still dependent in a way on sunlight.) However, most microbes are really small, and so don’t have simultaneous access to both the energy-rich reduced vent fluid and the oxygen-rich bottom water a few centimeters away. These free-living microbes have to make do with a little slice of that big redox gradient.
Some microbes, though, have figured out how to cheat (no doubt aided by their proximity to Satan) by corrupting normally-heterotrophic animals. Animals are big and have circulatory systems and respiratory pigments, so can access and transport both reductants and oxidants to their microbial overlords. They are rewarded for this with a constant stream of nutritive compounds. Consequently, many of these ‘autotrophic’ animals have, in their sloth, lost the ability even to participate in the sacred animal duties of Eating and Shitting.
Canonically, chemoautotrophic vent symbioses get their energetic electrons from hydrogen sulfide and dump them into oxygen. These days we’re discovering that it’s way more complicated than that. Different symbioses may utilize different sulfur speciesor even hydrogen as electron donors. In our paper, we found hints that some symbiotic bacteria may also be using alternatives to oxygens, like nitrate, as electron acceptors.
4) Do you know how and when people first figured out that symbiotic bacterial were the key to animal life in the deep sea?
A professor in my department, Colleen Cavanaugh did it as a first year graduate student. It was unbelievably insightful. People had just discovered all this insane animal biomass where it absolutely shouldn’t have been in 1977. Biologists got their first crack at the vents in 1979. Then two years later this upstart and incredibly badass young woman comes along and publishes the answer to the mystery in Science. She just schooled the whole world.
5) It is profoundly sick to collect RNA at the very bottom of the ocean and to turn that into data. Tell me how the ISMASH machine works.
Mostly it didn’t. When I started my PhD, my coadvisor Pete Girguis was like, “Jon, I want you to build a deep sea blender.” I was like, “sweet.” I had no idea what I was doing.
The concept is actually pretty simple. You want to 1) stop transcription, and 2) stabilize the RNA. Saturated solutions of ammonium sulfate are pretty good at doing both, since they precipitate the shit of RNA degrading enzymes and basically everything else.
The problem is that big animals can do a lot of transcription and RNA degradation before the preservative can make it into all the tissues. Molluscs are even worse, since they have shells. If you just dunk a snail or clam in RNAlater you might get an RNA profile of “suffocating slowly in horrible chemicals” instead of “happily oxidizing sulfide.” Which would suck. Thus Pete decided to just blend the shit out of them.
So me and this amazing guy Chris DiPerna spend a bunch of time in his buddy Paul’s shop in Southie fabricating a prototype. It plugs into the submarine’s hydraulics system to spin a motor to spin a literal set of Waring brand blender blades. Of course we have no way to really test it out so we pack it all up in the van and send it off to the South Pacific and just hope.
On the boat people think it’s just ludicrous, which of course it is, but how can’t you love it? You’re making snail smoothies in Hell. We plug it in and send it down and cross our fingers, and the amazing ROV pilots snag a snail and drop it in there and close the lid and hit ‘blend.’ All of this is being directed from the control van, which is sort of like the illegitimate love child between the bridge from the Starship Enterprise and a satellite news truck. (You can follow along at home in the online Virtual Van [http://4dgeo.whoi.edu/jason/]. Just pick the 2009 Fisher_LauBasin cruise on the left, click ‘virtual van’ and type in ‘blender’ in the search bar and hit ‘find.’) That first time it was the middle of the night and there were a ton of people in there, and everyone cheered. Or at least that’s how I remember it. But we couldn’t really tell if it worked until the submarine came up hours later.
Of course it didn’t work. I had no idea what I was doing.
So amongst all the other craziness me and the ROV guys (without whom none of this would have happened) keep hacking on these blenders trying to get them to work. The low point comes when we try to blend this wimpy diaphanous sea cucumber for an easy win. It came up looking like a very heavily used condom but otherwise intact [Editor’s note: LOL]
Eventually I take the advice of the guy who was literally driving the sub when they found the Titanic. We bolt some plastic rods to the insides of the blenders to break up the vortex, and BAM! Snail smoothies. We had just enough dives left to get the four samples that ended up in the paper.
6) Of the transcripts that you identified, only 12-13% of the eukaryotic genes matched known proteins. Do you think that’s because the sequencing reads you were getting were relatively short, or because these deep sea snails have radically different genomes from us land-lovers?
Probably the former, or something similar to that. That’s the neat thing about symbiosis: these animals get to acquire utterly unthinkable abilities without having to drastically modify their boring eukaryotic genomes. They’re actually pretty closely related to those orgy snails (aka slipper snails, Crepidula fornicata) you find on the beach here in the Northeast.
We really didn’t focus on the eukaryotic portion of the transcripts because of the sequencing depth — on average about a third of the reads were from the bacteria, but since the bacteria have about an order of magnitude fewer genes overall, the coverage was quite a bit higher. But there’s probably still some useful science to be done with those reads, for anyone interested. Available now for the low low price of free on MG-RAST.
When you think about it, it’s kind of insane that literally a third of mRNAs in these organisms are bacterial. I wonder what it would look like if you blended me whole and sequenced it?
7) Can you please vibe out with me for a minute about how incredible it is to go from live animals on the deep sea floor, to collecting them in a blender, to isolating the RNA, to sequencing the RNA, to generating a massive text file with all the raw sequence data, to actually putting all that into the framework of metabolic pathways, to actually understanding something about how energy is being created and used within cells at the bottom of the ocean?
It’s true. I had no idea what I was doing - Wouldn’t have happened without a ton of help. That’s what I love about science: on the one hand you’re standing on the shoulders of these intellectual giants, people who are good at writing code for the bioinformatics and people like Colleen Cavanaugh who have these incredible insights that open up entire fields and people doing all this insanely careful genetics work to figure out what all these genes actually do.
And on the other hand none of it works if you don’t know a guy in Southie who’s a crack hand welding aluminum or if you don’t listen to the sub pilot who discovered the freaking Titanic who’s telling you how to fix your goddamn vortex problem with a piece of plastic. Wouldn’t have happened without the molecular expertise of my awesome coauthor Roxanne Beinart or without Pete Girguis’s hyperproductive, hyperimaginitive deep sea fever dreams. Wouldn’t have happened without my mom and dad encouraging me to build stuff in the garage and to break the family computer over and over again while I figured out how to Linux in middle school.
You do all that and you go out on a boat and you figure out that this snail can basically eat hydrogen and breathe fertilizer. And that’s happening right now, on this stupid planet. You know nothing, Jon Snow.
8)What does “holobiont” mean?
These snails seem to be able to swap out their bacterial symbionts for different superpowers, depending on the local chemistry. Or, alternatively, the bacteria seem to be able to swap out their meatsuits. We think of ourselves as animals, so we tend to identify with the snail side of things. People want to know, what species of snail are you talking about? But if it’s really the bacteria that interface with the geochemistry, isn’t the identity of the bacteria actually the more important feature? And it’s even more confusing, since some snails only seem to partner with one type of bacteria, while others are more promiscuous (Alviniconcha/bacteria Facebook status: “It’s complicated”).
“Holobiont” tries to simplify things by taking the specific combination of partners as the unit of identity, rather than having to go through all these contortions about who’s hosting whom. I mean, jesus, they’re 1/3 bacterial RNA anyway. It’s also an attempt to subvert the dominant paradigm. #bacteriaforlife #euksareboring #YOLObiont
WE HERE AT SICKPAPES SALUTE YOU AND YOUR CREW, JON SANDERS!!!
If you ask me, one of the stupidest ideas out there is that of the “Man Cave.” The fact that a mainstream portion of my society thinks that the definition of manhood involves sitting in a specific room and watching TV and burning these remote-control-themed scented candles (or these ones) is nauseating, and I ask you to join me in weeping for the future generations of boy-children who will be raised with this double-whammy addiction to football and fucked-up aromatherapy.
That said, I’ll be DAMNED if there isn’t some seriously dope-ass research out there about some of the (actual) differences between men and women, and X-chromosome inactivation has got be near the top of the Hot column in this century’s “Research Topics: Hot-or-Not” list.
In mammals, XY individuals - those we often call “males” - carry a Y-chromosome, which contains a gene that initiates the cascade of developmental events leading to the growth of a male (including the development of male-specific organ known as the Butt). This is fine (and dandy), but because of this, females have twice as many X chromosomes in every one of their cells, which is not necessarily dandy because twice the chromosome means twice the mRNA levels of every gene on that chromosome, which could really harsh one’s mellow. In order to balance out the amount of transcription from genes on the X-chromosomes, every cell in the embryo of a female mammal shuts down one of the two X-chromosomes, completely silencing its expression. This is X-chromosome inactivation.
Probably the most famous manifestation of X-chromosome inactivation in action is the Calico Cat (editors note: complex internal rhyme unintended). The beautiful colors that besplotch the majestic Calico result from fact that pigmentation genes are located on the X-chromosome. During development, random cells throughout the cat inactivate either one or the other X-chromosome (each of contains a specific pigmentation gene), leading to the differential expression of pigment alleles in random patches of color on the adult’s fur. (Thus, all Calico cats are female, a fact that may surprise some of our readers who don’t already subscribe to Cat Fancy magazine).
The present pape addresses the molecular mechanism by which the X-chromosome shuts down. This process is known to involve a long, non-coding RNA (i.e. it doesn’t encode a protein product, but instead performs its biochemical handjob as an RNA) called Xist. Xist is transcribed from a specific location on the X-chromosome and then, in a bit of particularly trippy biological mystery, spreads to cover the entire chromosome over a period of hours like an iTunes visualizer, correlating with the cessation of transcription.
In this pape, a couple of major players in the game with, from what I can tell, infinity money, developed a technique to do time-lapse, deep-sequencing-based analysis of how the Xist RNA spreads to cover the X-chromosome during the process of X-chromosome inactivation. The first surprising thing is that Xist RNA doesn’t just leak outwards from its source along the length of the chromosome (like, for example, a two-dimensional pee stain on one’s shorts), but rather accumulates in very defined, specific spots across the chromosome (much like, for another example, forming a careful pee pattern in a snowbank).
The truly sick part of this pape, though, is that the regions where the Xist RNA accumulates are in fact the closest regions of the X chromosome in 3D physical space (not in 2D sequence space)! Because remember: the chromosome is packed into the nucleus like a crazily efficient, unknotted brick of uncooked Ramen noodles, so two points that are physically close in the nucleus may not actually be next to each other along the linear length of the chromosome. The model that the authors propose from their data provides quite heady visuals indeed, and we thank the authors for the opportunity to heartily update our mental imagery of one of the trillions of incredibly small machines working away in our cells.
Brenner, S., Jacob, F., and Meselson, M. 1961. An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature (4776): 576-581. [PDF]
Francois Jacob, our hero many times over, died on April 19, 2013. Much has been written about Jacob, including the most inspiring book of all time, his own incredibly-titled autobiography, and many simply jaw-dropping remembrances of his life and career (which didn’t even begin until the age of 30, prior to which point he was fighting against the Nazis as a military doctor). In light of this, we wish to pay our humble respects to Jacob by focusing in on one of his most truly moving papes, in which he helps figure out that mRNA is the intermediate messenger between DNA and protein. As someone who has grown up learning about DNA, RNA and protein from textbooks beginning at the age of 13, it is unspeakably humbling to realize that even such awe-inspiring knowledge as this was unleashed in the form of a single Pape. Given the torrential onslaught of meaningless papes which flood our poor inboxes daily, it is mindboggling to imagine what it must have been like when a pape of this stature and dignity could simply show up in Nature one week. We are all indebted to the True Pape such as this one, and we continue to pray for many more like it. In tribute to Jacob, we heartily recommend you enjoy his wonderful papes first-hand.
By the beginning of the 1960s, it was known that the physical basis of heredity was DNA, and it was strongly believed that the sequence of bases in DNA was co-linear with the sequence of amino acids within proteins. However, it was also known that DNA doesn’t leave the nucleus, whereas protein synthesis takes place in ribosomes, which are in the cytoplasm. The question, therefore, was how does the information get from the nucleus to the cytoplasm, and what is the molecular basis of this process? The best guess at the time was that each ribosome acted as a specialized template for a specific protein. Given that ribosomes are made of RNA, after all, it made perfect sense to imagine that the ribosomal RNA contained sequence-specific information which could encode a specific protein.
[At this point, as an aside, and just out of curiosity, would any of you know how to prove that mRNA is the messenger, even knowing the right answer beforehand? Even if you could go Back to the Future 2 with the book of correct answers to biology, could you figure out how to do these experiments to prove it? I sure couldn’t. There are those who believe that science progresses largely within social constraints, and that the intellectual contributions of specific individuals should not be hero-worshipped, and that somebody else would have figured it out pretty soon anyway. This may or may not be the case (it isn’t - you should definitely hero-worship Jacob and his crew), but I dare you to let this pape wash over your brain and not “need a minute” to collect yourself].
In any case, there is a true story where Jacob visits Brenner and Crick, and he’s telling them about his latest results implying the existence a short-lived molecule between DNA and protein, and they’re all at a party (probably much like the exact opposite of the moon-tower kegger in Dazed and Confused), then someone recalls a recent pape showing that after a virus infects a cell, there is this short-lived species of RNA that arises, which the authors hadn’t known how to interpret in their own pape, and then apparently everybody at the party starts screaming and Jacob doesn’t really speak English but picks it up quickly enough, and later that night they have all of the experiments planned out, and within weeks and they’re headed to Matt Meselson’s lab to use his ultracentrifuge.
The basic set-up is this: grow a bunch of bacteria in heavy nitrogen and carbon, infect them with the virus, and then transfer them immediately to a light medium. Any new products will be light, and any old products will be heavy, and the two can be separated by density in an ultracentrifuge in a cesium chloride density gradient (ground-truthed in Figs. 2 and 3). Using this set-up, they show that upon infection with virus, a new species of RNA is formed (Fig 4), which has a short half-life on the order of 16 minutes (Fig 5), and which associates with the old, heavy ribosomes (Fig 6). That is, the new RNA does not make new ribosomes, but represents a new, previously unknown species of RNA (the messenger!). They then show, using labeled sulfur, that the newly synthesized viral proteins, together with the new RNA, are also found on the old, heavy ribosomes (Figs. 7 and 8), disproving the idea that specialized ribosomes form each protein individually. Hallelujah!
In addition to figuring out one of the basic truths of life, there are two details of this pape which are particularly insane. (1) These experiments, with the exception of the sulfur stuff, were done by Brenner and Jacob in a period of four weeks, in a dirty basement, while visiting a lab that neither Jacob nor Brenner typically worked in. What’s more, the experiments completely failed for the first three weeks and the actual data was gotten in that one final week when no one believed in them. (2) The heavy carbon, which was necessary to separate out old and new ribosomes, was not just something you could buy. According to this great interview with Meselson, it did not exist anywhere in the USA or Japan, and so he got Linus Pauling to directly ask the head of the Soviet Academy of Sciences to make one gram of it for them, which they did by thermal diffusion, over the course of one full year. They delivered it to Meselson as a gas, which Meselson then turned into carbon dioxide that he fed to algae, which photosynthesized the heavy carbon into their bodies, which he then fed to yeast, which he then used to make yeast broth to feed the E. coli. Point is, these people were not kidding around at all, and we are eternally grateful for that.
Beadle & Tatum are basically the Cheech & Chong of biology, in that they are complete geniuses who were way ahead of their time. These were the two heroes who showed up in the 1940s when everyone was wildly speculating about the physical nature of these mysterious things called “genes” and showed that each gene gives rise to one single protein product (the so-called “one gene - one enzyme” hypothesis). Their famous experiments were done by inducing x-ray mutations in a fungus called Neurospora, and then showing that each individual mutation could be rescued by supplying a single, specific nutrient - in other words, that a single genetic mutation causes a single, specific fuck-up in a single enzyme. They even went the extra step of confirming that each of these mutations is inherited like a Mendellian recessive and was therefore a single gene.
The spine-tingling thing about the Beadle and Tatum experiments, though, is that they are so outrageously perfect and beautiful that it is truly terrifying to anyone who has ever tried to do an experiment one’s self. When I read the first Beadle and Tatum pape, it makes me feel like I’m a particularly stupid and tone-deaf 6-year old banging on some pots and pans, hearing the congo playing on “Life’s a Gas” for the first time - i.e. that it is time to throw in the towel because I’ll never achieve anything even approaching that level of perfection.
But buddy, if you are lucky enough (and have access to enough adderall) to have read Beadle’s Noble Prize acceptance speech, you will see that the elegance and clarity of his most famous work is largely the result of a set of earlier experiments done with Boris Ephrussi, which themselves are a LOT more like experiments most of us have attempted: insanely technically challenging, time-consuming and labor intensive, and although really suggestive of something potentially important, never really coming anywhere close to actually proving that potentially awesome thing because that goal won’t be attainable for decades.
Beadle and Ephrussi worked together at Caltech, studying the genetic control of eye-color in fruit flies. Fruit flies were already a powerful system for experimental genetics, so many different mutations had been isolated which gave rise to unusual eye-colors. Working with these different mutant lines, Beadle and Ephrussi physically transplanted the eye primordia from these different mutants into host larvae of different genotypes, making three-eyed flies (this was the psychotically difficult technical part). By reciprocally transplanting between these genotypes, they showed that two of the eye-color mutants (cinnabar and vermillion) were “non-autonomous,” meaning that it was the genotype of the host rather than the donor tissue that controlled the eye color.
The next part, though, is where the scary-genius shit happens. When a cinnabar eye is transplanted into a vermillion hosts, the eye remains cinnabar-colored. But when a vermillion eye is put in a cinnabar host, the eye becomes normal colored! Although this typically shouldn’t make sense to anyone who isn’t on Peyote, Beadle and Ephrussi came up with the idea that perhaps vermillion and cinnabar represent mutations in different genes within a single biochemical pathway that ultimately produce eye pigment. In other words, their idea was that the eye color pathway would be: “Precusor Substance -> Vermillion substance -> Cinnabar substance -> Pigment.” where the substances are diffusible throughout the host body, but interpreted locally within organs, and ultimately control eye color. Even when you know the answer it’s still confusing to think clearly about how this works, so it’s really jaw-dropping how these dudes were able to figure it out from scratch, before anybody else in the entire world understood what it might mean.
These experiments and their interpretation are so hot that my computer battery starts smoking every time I open the PDF. It’s like Beadle and Ephrussi stepped into an ancient temple completely brimming with confusing symbols and death-traps, yet were instantly able to shine the laser on the one specific key symbol that opens the trap door to all the gold coins. And its particularly cool to realize that from these really complex reciprocal eye transplantations, Beadle and the boys were already thinking that genes give rise to distinct biochemical entities, and that because of this, he could design the Beadle and Tatum experiments precisely to prove what he already suspected: that each gene encodes one specific product.
Gilbert, S., & Zevit, Z. (2001). Congenital human baculum deficiency: The generative bone of Genesis 2:21-23 American Journal of Medical Genetics, 101 (3), 284-285 DOI: 10.1002/ajmg.1387￼
Humans are the only primates that don’t have bones in their penises (dicks). This beautiful pape, reproduced in full above, proves that this is because God took the penis bone out of Adam to make Eve.
Though hilarious, this pape is actually a work of legit biblical scholarship by my scientific hero, Dr. Scott Gilbert, who literally wrote the book on Developmental Biology, and is the best teacher on the planet. Congratulations on your retirement, Dr. Gilbert!
Brennecke, J. et al. An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 322, 1387–1392 (2008).
In his classic song “Heart of a Woman" (Double Up; 2007, Jive/Zumba Records), R. Kelly lays out the list of qualities of women which make them so wonderful:
1) “[Women] take us and lift us up.”
2) “[Women] give us chance after chance and we still find a way to F things up.”
3) “[Women] love us so much our lies become the truth.”
4) “[Women find] a way to smile just to keep from showing [their] hurt.”
I know what you’re thinking: this is definitely a comprehensive list of the wonderful qualities of women. Yet, as impossible as it seems, the authors of this tear-jerking pape have identified yet another beautiful thing that the (fruit fly) ladies do for us: they give to their children an RNA-based adaptive immune system to combat parasitic pieces of DNA jumping around the genome which would otherwise kill us all.
Here’s the scoop: there are pieces of DNA called transposons which are capable of autonomously jumping around within our genome, landing wherever the fuck they want. This is a problem because if they land in the middle of a gene, its adios for that gene. So, we want to silence these transposon so they can’t jump around.
Its been known for a while that one of the basic strategies for fighting transposons is to silence large chunks of the genomes where these selfish bastards have landed, creating graveyards of inactivated transposons. There was a flurry of excitement in the early 2000s arose when dudes figured out that these graveyards actually get used to help fight active transposons. The cemeteries get transcribed into long pieces of RNA which are then chopped up into small RNA fragments and used as probes to find active transposons, which are then destroyed in a process playfully known as “the ping-pong cycle.” This is very cool because its conceptually similar to an immune system, where old invaders (transposons which are now trapped in the graveyard) are used as probes to search for currently active invaders.
What this nasty pape shows is that this transposon-fighting machinery is downright transgenerational. In other words, the small-RNAs generated by the mom are deposited into her egg cells which ultimately become the next generation. This gives the baby a head-start for fighting the transposons likely to be present in its genome. This observation helps make sense of the confounding observation that if you mate a heavily transposon-laden male with a relatively transposon-free female, the offspring all die, whereas the same cross with the parents’ sexes reversed is totally cool (because in that case the mom has had experience dealing with all the transposons so is ready to fight them with her up-to-date small RNAs). This is basically the fly equivalent of bribing the fancy pre-school admissions department so that her spoiled maggot-baby has all the advantages she had.
Gunkel, N., Yano, T., Markussen, F. H., Olsen, L. C., & Ephrussi, A. (1998). Localization-dependent translation requires a functional interaction between the 5“ and 3” ends of oskar mRNA. Genes & Development, 12(11), 1652–1664.
Today I’d like to speak with you about a very rare type of sickness that infects a small number of unique papes. It is a very natural and beautiful type of sickness, but I want to stress that this particular breed of sickness brings up certain themes which may not be suitable for children.
When a grown-up is doing experiments, he or she often gets results that don’t seem to make sense at first. The specifics are usually extremely esoteric, and such inexplicable results can make an Adult Scientist feel downright lonely [editor’s note: but we are always with you].
You go crazy trying to figure out what you could have done wrong - you ask your lab-mates, you email around to various professors to see if they can figure it out, you ask the haggard 65-year old post-doc downstairs whose translucent yellow fingernails have grown so long and curled he can’t grip his 2-liter bottle of Mountain Dew anymore - but no one can help you.
That is, until you stumble across the Holy Grail of Sick Papes: a pape which already solved your fucking problem for you and has since been sitting in a solid, non-show-off journal since 1998, just waiting to make you smile knowingly. Let this stand as a reminder to all you out there in the data game: if you do solid and honest work, it will always help others get truly nasty data in the future.
Its hard to express in words the respect I have for this type of pape. When you have stumbled across some unpredictable and hard-to-explain experimental result yourself and then you come to find that someone else already did a really hard, careful, patient set of experiments to figure out what’s happening? And back when those experiments were way harder than they are today? Its also a nice reminder that while a lot of jerkoffs want you to think that what’s important is the Impact Factor of a journal or your H-index, what actually makes a pape sick is the kickass-ness of its content, plain and simple.
In recent years, the Ephrussi lab was tragically infiltrated by a bullshit artist worse than Madoff. But, just as their science has always been awe-inspiring and timeless, they immediately dealt with this shit-head in a straightforward, honest, and open manner, and can now hold their heads high as an example of how to deal with a “lying fox in the chicken data house” as they say. Keep your hearts open everybody, and let love pour in!
Kawauchi, G., Sharma, P. & Giribet, G. Sipunculan phylogeny based on six genes, with a new classification and the descriptions of two new families. Zoologica Scripta 41, 186–210 (2012).
Photograph: Gonzalo Giribet
We at SickPapes recently sat down for some real talk with Dr. Gisele Kawauchi, one of the handful of experts on a phylum of marine worms called Sipunculids. While there are “science journalists” out there who only seem think a pape is sick if it involves sticking an autistic child with severe peanut allergies in an fMRI machine to figure out what parts of the brain light up while finding the cure for AIDS in an invisibility cloak, I wish to point out that some of the actually sickest science right now involves just trying to figure out what the fuck all these animals are all around us are, and how they’re related to each other. If this task sounds trivial to you, allow me to quote a douchebag I recently met at a party: “consider the following.”
A paper was published a few years ago which might as well have been called “No one has any idea what is happening all around us.” These daredevils went on a ferocious collecting quest, spending an unprecedented amount of time collecting marine molluscs in a tiny part of the ocean off the coast of New Caledonia. They used every possible collecting technique, from scuba diving to sieving sediment to crushing rocks to dissecting other animals, and finally came up with a total of how many molluscan species they had seen: 2,738.
Here’s the scary part: 48% of these species were represented by less than five individuals. Even with the world experts sampling as hard as they could in one little speck of the ocean, they were still getting tons of new stuff with every new sample. It is an insane joke to imagine that we will ever have a handle on the diversity of animals on this planet. If anyone ever tries to tell you how many species of animals there are on earth, you tell them: “Bring a knife.”
The exceedingly sick work of classifying and describing species doesn’t often get the funding or the adoration it deserves from the elite, left-wing Media establishment. We here at SickPapes therefore want to give a hearty shoutout to all the taxonomists out there pumping our tracks on the broken radios in the museums of comparative zoology across the world: we salute you big time.
Without further ado, let’s hear what a world class zoologist has to say to her borderline illiterate interviewer:
Mr. SickPapes: Gisele! As you know, I particularly like your recent paper because it is an in-depth study of a group of animals which many people do not even know exist, and about which very little is known. Until I met you, in fact, I had never seen a sipunculan in my entire life although I am a professional biologist. Where does one find these animals?
Dr. Gisele Kawauchi: Sipunculans are marine creatures commonly known as “peanut worms.” Many people have never seen one before, including professional biologists, so don’t worry - you are not the only one that was completely unaware of these creatures. Sipunculans live hidden in rock crevices, burrowing into the sediment, in empty gastropod shells or inside coral rubble. Consequently, they are inconspicuous, but can sometimes be found washed up on the beach after a big storm, or on the surface of the sediment during low tide period on a very hot day.
SP: Can you describe to me what a sipunculan looks like? Is there any part of the human male crotchal region that it resembles?
GK: The sipunculans are worm-like creatures with a body divided in two parts: a cylindrical trunk and retractable introvert that can be completely invaginated inside the trunk. At the anterior end of the introvert there is a tentacular crown surrounding the mouth. A peculiar characteristic of this group of invertebrates is that the anus is not at the opposite side of the mouth (at the posterior end of the trunk) as in many other wormy-like creatures, but it is at the anterior part of the trunk. We can say that sinpunculans has the anus on the neck. For the second part of this question I will let you decide if they look like any part of the human male body. You can see some pictures at the website sipuncula.lifedesks.org and come to your own conclusion.
SP: What was known of sipunculan taxonomy prior to your study? Did you perhaps once study with the guy who literally wrote the book about Sipuncula, whose tenacity in the face of blindness might be extremely inspiring to young biologists out there?
GK: Sipunculans are traditionally considered as their own phylum, but a number of recent molecular and genomic studies have suggested that they are derived annelids that have lost their segmentation. For this reason, sipunculans are a very interesting group for studies of evolution and loss of segmentation. They are in a group of invertebrates phyla called the Lophotrocozoa [editors note: hell yeah], distributed worldwide, and contain about 150 species currently recognized.
I first came to the US invited by Prof. Edward Cutler, who I met for the first time on a collecting trip to Barbados. He wrote the last compilation about the systematics, biology and evolution of Sipuncula, which summarized all that was known of this group at that time. I had the honor to work for about a year with him, before he passed away after years of fighting against prostate cancer.
Dr. Cutler was diagnosed with retinitis pigmentosa, a congenital disease [editors note: which causes blindness], when he was doing his PhD. He decided that this problem would not interfere with his studies and completed his doctoral degree in four years, writing his dissertation on the Sipuncula of the western North Atlantic. For years he continued working with Sipuncula with the help of his first wife Norma, and published a series of papers reviewing each genus within the phylum. In his book, Ed cleared up many problems in the taxonomy of the Sipuncula and reduced the total number of described species from about 300 to 149. His story definitely inspired me because even as his own abilities to work with the animals diminished, he endeavored to ensure that others would carry on his work, and I am glad that I was one of them.
SP: You have decided to create a new “family” of sipunculans, yet wouldn’t you agree that we animals are all, in fact, one big family? Wouldn’t you agree that the difference between humans and sipunculans is really just a semantic issue?
GK: The human being always needs to organize and classify everything, to understand the relationship between them. The decision to create a classification of organisms is a philosophical abstraction that we (humans) created to understand the multitude of life. Beyond that, for biologists to communicate with each other about these organisms, we need to classifify them into groups. And the classification should be meaningful, based on the evolutionary history of life such that it predicts properties of newly discovered or poorly known organisms.
My answer to your question if I agree thatthe difference between humans and sipunculans is really just a semantic issue is no. Each one has a unique anatomy, physiology and behavior, which make them different organism. I am not judging, I am a systematist, who studies the pattern of relationships among group of organisms to understand the history off all life.
SP: In your opinion, what is the point of studying anything besides fruit flies and mice? Since those are the two animals where they keep all the knowledge about human medicine, why study anything else?
GK: I think you equivocate when you affirm that fruit flies and mice are the animals that keep all the knowledge about human medicine. If you search for bio-active products from sea organisms or sea bio-technology you will find hundreds of references related to this theme. For example, studies with substances found in sponges called agelastatins have shown that these compounds have the ability to kill cancer cells. This substance was discovered in 1993, and since then chemists have been trying to synthesize this substance in the laboratory. Recently a group at MIT discovered the shortest and most productive way to synthesize all six of the known agelastatins (Movassaghi M., Siegel D.S., and Han S 2010. Total synthesis of all agelastatin alkaloids. Chem. Sci., 1, 561-566). Why study weird invertebrates? Because maybe the cure for many other diseases can be found in one Sipuncula or in any other obscure marine organism. So why not keep studying them?