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Field of Science
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No, not the annoying kind that secretly restarts your computer in the background because you just bought it and haven't gotten around to deactivating auto-update yet and told it to fuck off the last few times so it didn't pop up the window anymore because it was sad. Or the kind that Adobe's PDF reader mysteriously wants about four times a day. Just a very late bloggy kind.
Apologies for disappearing for a while there. Personal issues came up and didn't really feel like writing about science (or reading much about it for a while). Long story short, I'm may well be a failed scientist at this point (no grad school for me, yay), and the academic career is one of the few where once you fall off the track, it's practically impossible to get back on. And unlike in most other careers, the skills you acquire by that point are nontransferable anywhere else, meaning you're screwed, period. Add to that the worst economy since the Great Depression, and the party starts off with a bang. That said, I'll continue with my attempts to sneak past academia's fortifications under the cover of night, if no other reason than that banging my head against brick walls fucking arouses me.
Anyway, I'm getting back to blogging now. Should at least take advantage of the fact I still have a computer and internet; might be a bit harder to blog when unemployed and homeless ;-)
There are some exciting developments next month: one I can't tell you about yet as it's part of bigger news; the other is that I'll be going to a phycology-protistology meeting (PSA-ISoP) mid-July and will be officially blogging it! There's lots of awesome research going on in the area and I'm happy I'll be able to share some of it with you.
Microscopy Reddit Community - /r/microscopy
Every once in a while a stack of undeciphered micrographs appears before someone's conscience, and every once in a while a resolution of this issue is attempted by approaching yours truly. I'm still a novice to the realm of the small, and usually fail to identify creatures (or artefacts) in question, leaving behind a trail of disappointment and pristine befuddlement. Forwarding those images to friends and colleagues would be awkward, since those people have enough on their plate to begin with. In short, would be nice to have a centralised place where people could share images and others could voluntarily look them over and comment on them. Micro*scope/EOL is a nice image repository, but generally the images there are of good quality and are finished products; furthermore, I still don't know how to work the interface there despite having access privileges. What would be great is if people could host images wherever they like, and then link to them in a centralised place for discussion where anyone could participate. In other words, Reddit.
There already was a microscopy subreddit (a Reddit community), but it was largely inactive and abandoned. Anyway, I'm now a moderator there, and would like to develop it into a community where micrographs of all sorts can be shared and discussed, with emphasis on microbial organisms (but sliced up macrobes welcome too). Creating an account is really easy, as is submitting a link (just make sure it goes to /r/microscopy and not some other area of reddit). We need participants though, so if you have any neglected mystery images, please post them, and if you're in the mood to browse micrographs from time to time, feel free to stop by! Just keep in mind anyone can see the subreddit including the images, so careful with potentially publication-worthy data...
Hope to see you there!
There's a really awesome Russian underwater macrophotography blog I came across a while ago that you should all know about. The photos are stunning, mainly of pretty tiny inverts in the White Sea in northern Russia (and plenty of shots of Northern Lights and white nights and all that).
[Sticky proteins and complex relationships]
[(protein) Relationship drama: promiscuous proteins in small populations]
[Not all is good that sticks: non-adaptive complexity gain through compensatory protein adhesion]
[Man, I suck at titles]
NB: This post can be considered as part 2.5 of my In defense of constructive neutral evolution series; also recommended for some background are part 1, discussing selection, drift and Neutral Theory, and part 2, discussing Constructive Neutral Evolution; to answer a popular question, part 3 *will* materialise
Constructive neutral evolution is one mechanism of complexity increase without any associated increase in fitness – or, in other words, non-adaptive complexity gain. Basically, a random interaction between two proteins can lead to a fixed dependency if this interaction compensates for a mutation that was otherwise lethal – termed 'pressuppression'. In this way, previously unnecessary dependencies accumulate to make a very bulky, bureaucratic system that essentially does the same thing. We've all seen it in our institutions, and evolution is about as efficient.
Fernández and Lynch 2011 Nature paper, from here onwards referred to as "the paper".
Protein 'stickiness' can be enhanced by biochemical means. Proteins vary in stability, and themselves come in populations – generally, most are in the optimal conformation that is presumably functional, but some individuals are messed up. This happens well past the sequence and folding errors, and some perfectly 'normal' proteins can be in a suboptimal state at any given time. Clearly, this affects the overall efficiency of the protein – even if it's enzymatically awesome, the overall 'protein' as we biologists understand it (sans population aspect) would decline in efficiency if a large chunk of its population is in a misfolded state.
One aspect that pushes around the proportion of the protein in the 'right' conformation is how well it plays with water. It shouldn't be too surprising that hydrophobic regions induce instability. What was new to me, but perhaps old news to those who actually understood chemistry, is that the exposure of the polar(hydrophilic) protein backbone to water also has a destabilising effect – and not only that, but often more significant than that of exposed hydrophobic regions! This may seem counterintuitive – doesn't water like hydrophilic regions? And there lies our problem.
Water molecules are attracted to polar groups, and the amino acid backbone is quite polar. This means little water molecules wander in towards the backbone and form hydrogen bonds with it. The problem is twofold: first of all, the protein, like all molecules, likes to 'jiggle'. The more it can jiggle in its given conformation, the more favourable that conformation is thermodynamically since its satisfied by more states. Entropy, etc. (now we're *really* entering territory I know nothing about, since my phys chem experience is locked away by PTSD...). Hooking up this backbone with water molecules reduces its 'jiggle' room, and makes it less thermodynamically stable – making change to other conformations more probable, therefore possibly leading to more errors in the protein population.
Secondly, as detailed further in the paper, water likes to hang out with more of itself. Water molecules are happiest in foursomes, sharing four hydrogen bonds with their neighbours. When a creepy protein backbone emerges and lures an unsuspecting water molecule away into the protein's murky depths, the water molecule cannot form as many bonds with its fellows (or as many hydrogen bonds, period), and is really sad and lonely. Or, in proper terms, the system becomes less stable, since thermodynamics will favour an arrangement where these water molecules are all happily coordinated with each other, and not being molested in a corner by an amino acid polar group. In other words, exposing the polar backbone (Solvent-Accessible Backbone Hydrogen Bonds, SABHBs in the paper) to water induces what is called Protein-Water Interfacial Tension (PWIT).
One way this tension can be released and the backbone exposure ('coded for' by genes, by the way) can be compensated for is if a random other protein (or more of its own kind) are recruited to cover that exposed backbone. This would help stabilise the protein conformation, and allow this potentially deleterious drawback to be tolerated (and get fixed in the population). Ultimately, the second (and third, etc) protein can become exapted for something useful, although just an eventual dependency is good enough to make sure these proteins stick together permanently. The crazy web of interactions gets crazier.
Fernández & Lynch's fig1a suffices perfectly but I like making diagrams, so I made one anyway. See text.
Now I'm about the last person to willingly blog about biochemistry, and this seems to have little only a distant relevance to evolution, particularly the non-adaptive kind that fascinates yours truly. It will make sense in a bit. Recall from a few seconds ago (hey, already difficult for some of us) that protein instability leads to reduced protein efficiency. This reduction is generally tolerated, however, until it's bad enough to have a higher chance of being removed. Recall from [what should be] introductory population genetics that selection acts probabilistically, with true slightly deleterious mutations have a lesser, but still significant, chance of fixation than strongly deleterious mutations, which selection has a higher chance of taking care of before drift quietly fixes it. (more detail in older post here) Since proteins are, quite unsurprisingly, also governed by fundamental principles of population genetics, drift becomes involved there too.
As populations get smaller, drift becomes a more dominant force relative to selection, and the window of 'effectively neutral' mutations – slightly beneficial and slightly deleterious, but unlikely to be dealt with by selection – increases. More mess is tolerated. This means more protein inefficiencies are allowed to fix in the population, those induced by backbone exposure among them. Since there are now more proteins that are no longer happy with themselves (or, rather, have an increased Protein-Water Interfacial Tension), they are more likely to stick together for biochemical stability. And here Constructive Neutral Evolution can come in too, allowing further deleterious mutations that are now presuppressed by the recruited proteins. In a way, this greases the presuppression process, rather than competing with it as this BBC news piece made Ford Doolittle appear to suggest.
Now, this is all great in theory, but is there any real data in support of this? For one thing, there is a clear increase of interactome (set of all interactions in an organism) complexity correlating with decrease in effective population size, suggesting a link between lax selection and accumulating complexity. Furthermore, the proteins in organisms of these smaller populations have more blistering backbone exposures to water. Supporting the relationship with population size further yet with the advantage of more phylogenetically independent events (but less interactome data), bacterial intracellular endosymbionts consistently exhibit higher protein backbone exposure (hydration) than their free-living counterparts. Selection appears to disfavour not only polar backbone exposure (also described as 'poorly wrapped proteins' in the paper), but once again, the rise of interaction complexity as a whole. (Fernández and Lynch 2011 Nature, in case you somehow managed to miss that)
Obviously I like this paper because it adds another mechanism to the arsenal of evolutionary processes happening independently of adaptation. But moreover, I don't think one can find too many examples of biochemistry mixed with population genetics. You hardly find cell and developmental biologists thinking about population genetics, and perhaps many biochemists have never even been exposed to such a subject. When fields that should never come that close together do, some really nice explosions of insight can occur (my sad attempt at chemical metaphors). We really need to talk to other more, and maybe even wander over to other departments from time to time. It's sometimes (often) frustrating to communicate with those strange ones from afar, but just like ethnic xenophobia, its interdisciplinary counterpart must also be overcome.
Figure 2a annoyed me a little as it ignored phylogenetic relationships, which is a big no-no when comparing properties of taxa. The figure is technically fine, especially since there aren't any correlation analyses there, but it's hard to discount phylogenetic history as being the cause behind the correlation of the traits without actually the characters on a tree. Anyway, since I like playing with data and running statistical analyses on things, especially when I didn't actually have to go through the pain of obtaining the data myself, I mapped some characters (interactome complexity from fig2a) on a phylogeny:
Unfortunately, even the most basic statistical operations become an epic headache when trees are involved, and very quickly things become painfully complicated, for the human as well as the computer. Especially when you're handed a dataset of mixed categorical and continuous characters, as I learned the hard way last night. After fighting Mesquite for a good many hours, I finally had to resort to extracting the Ne*µ (effective pop size * mutation rate; roughly put, both lead to increased selection efficiency) estimates from Lynch & Conery 2003 – relying on an intersection of two datasets meant that our taxon sampling was quite sad by the end of this enterprise. Anyway, I ran a pairwise comparison test (Maddison 1999 J Theor Biol) on the data, which probably isn't the best thing ever, but I got something resembling significance: p = 0.019. Depending on how statistically noisy your field is, you may even deem this acceptable. In any case, not too bad given my crude (and somewhat clueless) analysis and limited taxon sampling:
I mostly did this because I thought it'd take a couple hours max. If hours meant days, that wasn't too far off... but hey, I learned something!
Acknowledgments: thanks to Lucas Brouwers for helping me wade through the heavy biochemical stuff, and to Mike Lynch for explaining the key idea of the paper a while earlier. Otherwise I would've probably been too daunted to even read it, let alone blog about it...
Oh, and my Twitter people for random phylogenetics advice ;-)
Fernández, A., & Lynch, M. (2011). Non-adaptive origins of interactome complexity Nature DOI: 10.1038/nature09992
[will add some supplementary refs once I return to internet on Monday...]
*Or perhaps something happened to both that made them prone to evolve this bizarre system.
Genomic quirks are not just interesting in their own right as some arcane oddities, but can reveal a great deal about the dynamics of genomes in general. The dinoflagellate splice leader system turns out to yield a very crisp illustration of the power of ratchets and the toll of reverse transcription on genomes.
To reiterate, every single nuclear gene transcript in a dinoflagellate must be spliced with the 3'cap-bearing 'splice leader', or else it simply won't work. This means that the dino is full of mature transcripts with splice leaders attached to the transcribed genes. Enter reverse transcriptases, which are prevalent in probably most, if not all, eukaryotic genomes, thanks to viruses and their partners in genomic parasitism crimes, transposons. When they're not busy moving transposons around and helping viruses move in, they reverse transcribe random gene transcripts for fun, that may then, on occasion, be successfully recombined back into the genome. This process probably doesn't happen [successfully] every day, but over thousands or millions of years (and countless individuals) is rampant enough to leave a noticeable trace in the genome.
So we have a load of transcripts floating around with an extra sequence stitched onto them from the splice leader. Do the reverse transcriptases care in the slightest? Of course not: to them, a ribonucleotide is a ribonucleotide, give or take some trace biophysical stuff that might make a couple people cringe at what I just said. (meaning, I wouldn't be surprised if there could be some slight but ultimately detectable biases there too) This means that splice leader, on occasion, actually makes its way back into the nuclear genome attached to the beginning of the gene.
Mmmm, actual data! Note how the oldest SL piece closest to the gene (on the right) is the most degraded. (Slamovits & Keeling 2008 Curr Biol)
Splice leader trans-splicing not necessarily promoting reverse transcription – only makes it easier to detect. In other words, it inadvertently makes for a wonderfully convenient system where you can actually track what happens to a gene after it gets reverse transcribed. Once the gene makes its new home, the old gene copy is still present and they generally would be functionally redundant, so the dual-copy state is extremely unstable as ultimately the loss of one of the copies will be tolerated. If the newly transcribed copy is lost, we never see it and thus don't talk about it in the first place. However, once the clean original is lost, only the gene with the crap from the splice leader remains, and reversal to the original state is so improbable it's practically impossible. In other words, this process is a wonderful example of an evolutionary ratchet.
This ratchet example is therefore an elegant case of evolutionary direction that's not particularly well explained by the central dogmas of Modern Synthesis or (neo)Darwinism, where selection is the force that crafts order and directionality, with mutation a mere passive provider of material to be molded. I will go into a deeper discussion of this in another post (there's a cool paper coming out soon), but I think it's worth briefly mentioning here too while we're at it. The "mutation" step (to which, I guess, this trans-splicing and reverse-transcription process can be awkwardly attached) here is what provides a drive, a push in a certain direction, and towards increasing complexity, no less (although that last detail is irrelevant). While selection is present and provides constraints (if both genes are lost, for example, the organism dies), it does not do the 'driving' or 'forcing' in this system. Very crudely put, selection here is the passive phenomenon, and mutation is at the wheel.
Another case of intrinsic directionality, but where reversal is allowed, is your garden variety directional bias – where proceeding in one direction is more probable than going backwards. A very basic example of that is if the replication machinery favours a certain type of nucleic acid – left to its own devices, the genome base composition would be skewed in that direction. Boundaries can also induce an apparent directionality, but in this case it's no longer intrinsic... that's, again, a topic for another day.
This idea was a part of the Mutationism theories in the early 20th century, which were a little extreme and perhaps premature, since mutation was far from being even marginally understood at the time. In the usual melodramatic manner characteristic of academia and the scientific community, the pendulum swung far to the opposite extreme, and Modern Synthesis was born. It became heresy to think that mutation itself can actively contribute to direction and order. The field became engulfed in a false dichotomy, where either selection or mutation can actively provide direction, with the modern folk siding with the former. That is a serious mistake and an unnecessary waste of great explanatory potential – you can go so much farther with selection, drift, mutation and recombination all at the wheel, each pulling with different magnitudes in various directions. Well, technically, you wouldn't if you were the thing being pulled – which resonates so well with the absense of 'ascension' or general active directionality in the evolutionary system as a whole. Evolution is a slow, painful, inefficient and rather stochastic process, partly because the cart is being pulled in so many ways.
(The latter part, concerning directional biases and Mutationism, is based on various publications and conversations with Arlin Stoltzfus and Dan McShea, whom I gratefully acknowledge. =D)
McShea, D. (2001). The minor transitions in hierarchical evolution and the question of a directional bias Journal of Evolutionary Biology, 14 (3), 502-518 DOI: 10.1046/j.1420-9101.2001.00283.x
Slamovits, C., & Keeling, P. (2008). Widespread recycling of processed cDNAs in dinoflagellates Current Biology, 18 (13) DOI: 10.1016/j.cub.2008.04.054
Stoltzfus A (2006). Mutationism and the dual causation of evolutionary change. Evolution & development, 8 (3), 304-17 PMID: 16686641
Protistology Q&A on Reddit
And now to randomly show off a random Haptorian ciliate – meet Litonotus, a vicious predator armed with terrifying toxicysts, which you can see as long narrow things in its cytoplasm. Also note the two prominent macronuclei visible as clear-ish round areas in the cell. Litonotus is cool and all, but the bastard preys on creatures like Euplotes, which are kind of adorable (imagine Litonotus eats kittens...that's how bad it is). Nature is red in
Apologies for the delay – am behind on pretty much everything and frantically trying to tie up loose ends of my degree, fun times. Also, it's kinda awkward to write up a carnival post with only THREE submissions – you guys really need to submit more and/or write more MolBiol posts!
It seems molecular biology doesn't get blogged about specifically as much as evolution and diversity – perhaps because molecular biologists are usually busy troubleshooting their PCRs and RNA work for weeks on end, and have little time left over to write. In fact, judging from recent woes experienced by some of my lab buddies, I'm beginning to doubt the existence of RNA and believe it may all be a giant elaborate hoax invented to enslave more grad students. Have any of you ever *seen* RNA? That's what I thought...
This month we have a very biochemical (post-translational, if you will) MolBiol Carnival featuring enzyme spec, cyanobacterial biofuel precursors and some sweet diastereomer metabolism regulation.
Christopher Dieni at BitesizeBio has a nice write-up on measuring enzyme kinetics using UV spectrophotometry, complete with procedure, tips and troubleshooting – the kind of thing you wish accompanied every assay you've been assaulted by. Not being anything close to a biochemist, I had no idea you could actually observe enzyme action using something as simple as a spec, so this is quite cool!
Cyanobacteria and biofuel production
With growing concerns with using land plants for biofuels (for one thing, kind of odd to use food to power cars when not everyone has enough of it...), increasing attention has been turned towards algae eukaryotic and not. For one thing, algae are already quite good at photosynthesising and are vastly more abundant than plants, and arguably have the largest contribution to global photosynthesis – not surprising given the earth's surface is 70% ocean. Michael Scott Long at a NASW.org blog explains recent developments in genetic engineering and domestication of cyanobacteria for fatty acid production.
Diastereomers and regulation of metabolism
Stereoisomers are the beginning chemistry student's worst nightmare – they're so similar and easy to mix up, particularly if you're like me and can't tell left from right to begin with. However, a bacterium (rather, its enzymes) would have little trouble with the stereochemistry portion of a intro biochem class – to them, stereoisomers are day and night (and other things). Glucose and galactose are 'close enough' to each other for a biochem student, but a flipped arrangement at just a single stereocentre is enough to require a whole new set of enzymes and drastic changes in the pathway. E.coli prefers glucose, but can also process galactose (compromising its growth rate) by embellishing its metabolic pathways a little – the products of galactose digestion are sent to the tricarboxylic acid cycle via the glycoxylate shunt. Becky Ward at It Takes 30 discusses how sugar type availability affects the transcriptional regulation of this glycoxylate shunt, among other things, featuring a galactose-loving mutant.
This was fun. Wish there were more submissions – having to write up random blog posts forces me to revisit forgotten subjects and explore new ones: I'd never brave a post on metabolic regulation on my own! By not submitting, y'all are having a deleterious effect on my education... ;-)
The next edition will be hosted by our resident microbiologist @labratting at Lab Rat, and she better get more than three submissions... come on, we do so much molecular biology in almost every field of biology! Write 'er up, dammit!