This is when *I* need a good science blogger

Today you get to meet yet another of my random interests: the origin of life. (Is there a person with an interest in living things who isn’t fascinated by the origin of life?) And, since we sciencey types are very anxious about personal biases, I might as well start with a confession.

I love the RNA world hypothesis.

It was just one of those things that you learn at school/uni (I think it was 1st year molecular biology for me), and it’s so neat and elegant and compelling that you immediately fall in love. Sure, later, when you’re out of the inevitable simplicity of class, you learn about the nuances. The difficulties. But the evidence for still seems so convincing that you have no doubt that we’ll eventually solve the problems.

In case you aren’t familiar with it, the RNA world hypothesis is the leading solution to the chicken and egg problem that is the “central dogma” of molecular biology (diagram from Wikipedia):

DNA is great genetic hardware, but it’s nothing without proteins. Proteins are encoded in DNA, but the code is useless without proteins to read it. Making DNA requires proteins. But the proteins come from the DNA code. You see where this is going…

RNA takes the stage

The RNA world is an ingenious idea that elevates RNA from being merely the messenger between DNA and protein to centre stage. While its big brother DNA is a fairly stable and inert molecule, RNA is much more chemically active. It doesn’t like languishing in long, stable double helices – rather, it folds up into all kinds of odd shapes that can, surprisingly, catalyse a variety of chemical reactions. Just like proteins. Yet the “letters” of RNA can form complementary pairs, allowing for faithful copying. Just like DNA.

And, so the theory goes, there was a time when RNA was both the genome and the enzymes (enzymes made of RNA are called ribozymes). The right sort of RNA molecule could have copied itself without proteins [1], and performed whatever chemistry a primitive life form needed – also without proteins. Crucially, the right sort of RNA molecule could have invented proteins [2].

One of the key revelations to lend support to the RNA world hypothesis is that proteins in cells today are still made by RNA. Proteins are manufactured in ribosomes. A modern ribosome is a very complicated structure made of several folded-up RNA molecules and dozens of proteins. However, investigations of its structure (see Cech [2000] for a quick review) revealed that the place where amino acids are joined into a protein chain is all RNA – the proteins may support the RNA, but it seems to be the RNA that actually does the job.

Beautiful hypothesis vs. ugly facts?

So, everything is shiny and awesome and exciting. Ribozymes capable of all sorts of interesting chemistry [3] abound, and we have some very neat ideas regarding how RNA paved the way towards the modern protein-and-DNA world [2].

And then Harish and Caetano-Anollés (2012) come along, and I don’t know what to think.

A large part of the problem is that their methods go way over my head. I get the gist of their message. They figured out the relative ages of the RNA and protein components of the ribosome. The protein-synthesis parts – RNA and protein alike – turned out relatively new. They also found that the oldest protein parts interact with the oldest RNA parts – and seem to have coevolved. That, they say, would suggest that RNA and fairly large pieces of protein had a common history together before the future ribosome became capable of making proteins.

Yes, that means either that RNA didn’t invent proteins, or at the very least, that the “inventor” was not a precursor of the ribosome.

I really really don’t want to believe the former, and the latter possibility is a butchery of Occam’s razor without further evidence. But what else is left, if the study is correct?

One part of their results that I found intriguing is the structural similarity of the most ancient parts of ribosomal RNA to – you’d never guess – lab-evolved RNA-copying ribozymes. That is… oh, I don’t really know what it is, aside from “fascinating”. Did the ribosome start out as replication machinery, and turn into a protein factory only later? Or are the structures similar because reading the primitive genetic code required the same sort of molecular machine as copying RNA? Or is it even just coincidence?

And this is why I need a good science blogger. I need someone who deeply understands the paper and can translate it into something I can digest. Because at the moment, I can’t make heads or tails of this. I’m rather attached to the RNA world; it makes sense to me, and as far as scientific hypotheses go, it’s simply beautiful. Yet I can’t point to any obviously bullshit reasoning in the new study, other than where they seem to imply that because modern ribosomes need proteins to work, proteins must have been present in the ribosome from the start. (Which is a bit like every damn irreducible complexity argument advanced by creationists.) I just don’t have a good enough grasp on the methodology to tell whether it’s all solid or whether any of it is dodgy. Words fail to express how much that bugs me.

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Notes:

[1] Lincoln and Joyce (2009) and Wochner et al. (2011) came tantalisingly close to making/evolving the right sort of RNA molecule in the lab. The former’s pair of ribozymes can only copy each other by stitching together two half-ribozymes, but they can keep going at it forever and ever. Wochner et al.’s molecule can copy RNA using single letters as ingredients, but it runs out of steam after 90 or so of them. That’s several times better than the previous record, but still not long enough for the ribozyme to replicate its twice-as-long self.

[2] This excellent video describes one way it could have happened. When it comes to science education, cdk007 never fails to deliver!

[3] Including attaching amino acids to other RNA molecules (Turk et al., 2010) – look up tRNA if you don’t see why this is exciting 😉

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References:

Cech TR (2000) The ribosome is a ribozyme. Science 289:878-879

Harish A & Caetano-Anollés G (2012) Ribosomal history reveals origins of modern protein synthesis. PLoS ONE 7:e32776

Lincoln TA & Joyce GF (2009) Self-sustained replication of an RNA enzyme. Science 323:1229-1232

Turk RM et al. (2010) Multiple translational products from a five-nucleotide ribozyme. PNAS 107:4585-4589

Wochner A et al. (2011) Ribozyme-catalyzed transcription of an active ribozyme. Science 332:209-212

And now, a Coronacollina rant.

Coronacollina aside: great discovery + science communication fail = grumpy Mammal.

Now that we’ve drunk a few metaphorical beverages of choice to the melodiously named little sponge, allow me a rantish tangent on the terribly written press release that accompanies the paper. It makes me roll my eyes right off the bat by saying that “life” exploded in the Cambrian. No, no, no. Animals did. Plenty of other life forms didn’t, far as I know.

This, especially the part I bolded, just seems to come out of nowhere: “The finding provides insight into the evolution of life — particularly, early life — on the planet, why animals go extinct, and how organisms respond to environmental changes. The discovery also can help scientists recognize life elsewhere in the universe.” Excuse me, but where the fuck did that come from? Needless to say there’s not a word about extraterrestrial life in the entire paper, and not much about extinction or environmental change, either.

Then the article goes on to, well, not so much “suggest” as outright claim that no Precambrian animals with hard skeletons were known before this discovery: “’Up until the Cambrian, it was understood that animals were soft bodied and had no hard parts,’ said Mary Droser, a professor of geology at the University of California, Riverside, whose research team made the discovery in South Australia. ‘But we now have an organism with individual skeletal body parts that appears before the Cambrian.’” Cloudina and Namacalathus beg to differ, and I would bet money that Mary Droser knows this. In fact, Cloudina is referenced in the paper as an example of Precambrian hard parts. I’m undecided on what’s worse, if Droser fibbed about the fossil record, or if whoever edited her comments was clueless. And this is a fairly important piece of information, as the truth makes the significance of poor Coronacollina slightly less obvious. (Hmm…)

The next “highlight” (lowlight???) is where it says Coronacollina was constructed like Cambrian sponges. No, it was constructed like a Cambrian sponge, and an unusual one at that. There were many other Cambrian sponges that looked nothing like these prickly cones, see an assortment from the Burgess Shale here.

Then comes this characterisation: “[C. acula was s]haped like a thimble to which at least four 20-40-centimeter-long needle-like “spicules” were attached…” Um, someone didn’t read the paper here. It’s at most four in the known specimens, although the authors do speculate that there could’ve been more in life. And the lower end of their lengths has one fewer zero…

The crowning misreading near the end: “Droser explained that the spicules had to have been mineralized because the casts show they are ruler-straight. Moreover, they broke.” Dear article writer, I don’t know what she “explained” in person, but the paper describes the spicules (bolding mine) as “straight, rigid structures that were most commonly broken once disarticulated. Some spicules display a slight deviation from ruler-straight, implying either a composition of chitin that was plastic during life, or a mineralized composition of biogenic silica or calcium carbonate preserved deformed due to plastic behavior postburial” Newsflash: chitin is not a mineral. Granted, later in the paper they reason that some sort of mineral is most likely due to the apparent brittleness of the spicules, but they clearly don’t rule out a mainly organic composition.

Grah. I hate how press releases often get so many things wrong, and this one isn’t even a decent piece of writing. Disappointing doesn’t even begin to describe it.

The shadow of a skeleton

Sponges are in a generous mood these days, as far as exciting discoveries are concerned! First Otavia breaks the record for oldest known animal, and now Coronacollina (what a pretty name!) shows up with what looks like the oldest hard skeleton in the animal kingdom.

Hard skeletons* are a real success story in the history of life. From the tough organic support structures of trees to our own strong and versatile bones, they’ve revolutionised (or, in the case of trees, pretty much created) ecosystems. (We also owe them some gorgeous landscapes.) Skeletons really came into fashion during the Cambrian explosion, when incorporating minerals into shells, spikes and other hard parts became commonplace among animals. However, there are a few examples of animals with hard parts that are older, mainly from the very end of the Ediacaran period just before the dawn of the Cambrian. Our spiny new friend does one better than those, hailing from the heyday of Ediacaran creatures.

Coronacollina acula (Clites et al., 2012) is described as a smallish creature similar to the Cambrian sponge Choia. Its 300+ specimens were preserved as imprints that show every sign of having come from a fairly solid animal. The body is kind of cone-shaped with what appears to be threefold symmetry. Most intriguing are the traces of long, thin spikes that radiate from the main body of many specimens. There are up to four of them, fewer than Choia had, and they were clearly made of a hard material in life: the grooves they left are straight as arrows, narrow and sharply defined, unlike a trace left by a soft structure. Like the more numerous spikes of Choia, they may have acted as stabilisers/struts to keep the living sponge from being upended by waves.

(From my perspective, it’s a pity that only the imprints were preserved. I have an occupational interest in biomineralisation, so I’d really like to know what the spicules were originally made of. If Coronacollina is a relative of Choia, odds are they were either organic or, if they were mineralised at all, made of silica. Interestingly, the authors bet on some sort of mineral because the spicules broke so often, as though they were quite brittle. I would’ve thought that mineralised structures would leave more than imprints, but apparently the chances of silica or calcium carbonate skeletons being preserved in coarse sandstone aren’t that great. You learn something every day…)

Clites and colleagues consider the creature important for two reasons: first, because it is the oldest known example of an animal with a hard skeleton. The shadows of its long thin spikes in the rocks foreshadow, so to speak, of the age of skeletons that came with the Cambrian. Second, finding an Ediacaran animal that can be related to something outside its own weird contemporaries is always worth a little celebration! 😉

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Note:

*The word “skeleton” is used in a very loose sense here. It includes any hardened structure that gives support and/or protection to some part of an organism. Bones, shells, armour plates, teeth, perhaps even the protein meshwork that gives bath sponges shape, can belong here.

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Reference:

Clites E. et al. (2012) The advent of hard-part structural support among the Ediacara biota: Ediacaran harbinger of a Cambrian mode of body construction. Geology advance online publication (doi: 10.1130/G32828.1)

News bites

Since work is quite frantic lately, and my attention span has gone on holiday, I’ve decided to do something I haven’t done before and just say a few words about papers that caught my interest today without actually reading them. Each of these is probably worth a full-blown meandering of its own, but I know I wouldn’t ever get to them at this rate. Better read their abstracts and give some quick thoughts than let them sink unnoticed into the murk of my “papers” folder!

(1) How many genomes do we (not) have?

Reference: Ali Abbasi A & Hanif H (2012) Phylogenetic history of paralogous gene quartets on  human chromosomes 1, 2, 8 and 20 provides no evidence in favor of the vertebrate octoploidy hypothesis. Molecular Phylogenetics and Evolution, in press (doi: 10.1016/j.ympev.2012.02.028)

(How many papers have authors with alliterating names? :D)

In the circles I move in, it’s pretty much canon that the ancestors of living vertebrates doubled their entire genomes twice. It’s still debated exactly when these duplications occurred, but few people doubt that they did. This so-called 2R hypothesis is supported by things like our possession of several (quite often, four) copies of genes that are singletons in our closest living relatives (read: lancelets*), and more importantly, that whole big chunks of lancelet chromosomes can be matched to chunks of four different vertebrate (mainly, human) chromosomes. Genes that are close to one another in lancelets are often also close together in vertebrates.

The relationship is not perfect – in well over 500 million years of evolution, genes inevitably get lost and bits of chromosome scrambled. And, thus, there is always room to question the 2R scenario, which is what this paper clearly does. They propose that those four-gene families originated at all sorts of different times, from small local duplications and rearrangements. If they are right, this is a very important result. It basically uproots every bit of speculation ever proposed on how the genome duplications contributed to the evolution of vertebrates, which, far as I can tell, is a hell of a lot of speculation. Not having read the whole paper, I would still put my money on 2R, but who knows what the future holds? Maybe we are facing a minor paradigm shift?

(2) The segmentation clock also ticks in insects!

Reference: Sarrazin AF et al. (2012) A segmentation clock with two-segment periodicity in insects. Science, advance online publication (doi: 10.1126/science.1218256)

The evolutionary history of segmentation is one of my random interests, and from my point of view, the above is a good reason to squee in a most fangirlish way. Segmentation is the construction of a body from repeating units. In its purest form, which isn’t that common in modern animals, the animal is essentially made up of identical repeated blocks containing a copy of each key organ like kidneys, nerve centres, limbs and muscles. (Even in the most perfectly segmented creatures, head and tail ends form something of an exception. Ragworms make a nice example.) More commonly, only some components are repeated, and they are repeated with slight differences along the body. Vertebrates’ spine and associated muscles are a good example, and so are the defining traits of arthropods, their jointed exoskeletons equipped with repeated pairs of appendages.

Although traditionally it has been thought that arthropod and vertebrate segmentation have independent origins, parts of the genetic machinery are shared between both groups (as well as segmented worms). Various “segmentation genes” are active in distinct stripes in our embryos, marking out future segments even before we can see the segments themselves. In vertebrates, cells periodically switch “segmentation genes” on and off, and this combined with the growth of the embryo produces a dynamic stripey pattern of gene expression. While segments and stripes of gene expression are darn obvious in arthropods, this is the first time anyone has confirmed that some arthropod segmentation genes actually oscillate like their vertebrate counterparts do, as opposed to, say, the cells expressing them moving about. Whether this is a spectacular example of convergent evolution or evidence of a shared ancestral heritage, I couldn’t say, but it’s really cool either way.

(3) Old genes are entrenched, new genes are redundant after all?

Reference: Chen WH et al.(2012) Younger genes are less likely to be essential than older genes, and duplicates are less likely to be essential than singletons of the same age. Molecular Biology and Evolution advance online publication (doi: 10.1093/molbev/mss014)

So, this claims to resolve a conundrum I wasn’t even aware of before. Gene duplication is thought to be important for the evolution of new functions because two copies of a gene mean there is a backup if one of them fails at its original function. Hence, theory goes, duplicate genes are much less restricted in the evolutionary paths they can take. Apparently, studies in mice have contradicted this common wisdom by claiming that duplicate genes are just as likely to be indispensable as genes without backup copies. However, Chen et al. are saying that this is wrong, confounded by gene age. Since new genes are less likely to be essential than old genes (which had more time to evolve interactions with the rest of the genome), and mouse duplicates are on average older than mouse singletons, the two effects end up cancelling out. When they factor in gene age, duplicates are indeed less essential than loners. One of the central tenets of current thinking about (genetic) novelty stays in the ring for another round…

(4) Is reducing complexity easier than increasing it?

Reference: Harjunmaa E et al. (2012) On the difficulty of increasing dental complexity. Nature advance online publication (doi: 10.1038/nature10876)

How complexity increases in evolution is more than a breeding ground for creationist incredulity, it’s also quite interesting for bona fide evolutionary biologists. Looking at the development of mouse teeth, Harjunmaa et al. notice that increases and decreases in the complexity of tooth shapes require different sorts of mess-ups. Simpler-than-normal teeth are common in mutants and easy to make in experiments. More complex teeth – i.e. those with more cusps – are rarely if ever seen in natural mutants. Turns out they are perfectly possible – you just need to manipulate several genetic pathways at the same time to produce a clear result.

Can this be generalised? Is greater complexity usually harder to achieve? When does this apply and when does it not? I’ve recently read papers that explore how complexity increases easily and completely by chance (I have a half-written post about them languishing on my hard drive, FWIW). Are the rules different for different levels of organisation? The aforementioned complexity-by-chance papers analyse the molecular level: one is about the architecture of gene switches, the other about a protein machine. Teeth are pretty large pieces of life with thousands upon thousands of such machines participating in their production. Does that make a real difference, or is what I’m seeing just coincidence? Dunno, but it’s fascinating to think about!

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Heh, it looks like I took rather bigger “bites” of these news than I planned to. I kind of managed to write the equivalent of a full-blown meandering anyway. The only difference is that I didn’t painstakingly reference this one. I hope that doesn’t mean that half of what I wrote off the top of my head is wrong 😀

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Note:

*Lancelets are now not considered our closest relatives. Unbelievable as that may seem, that honour goes to sea squirts and their ilk. However, the sea squirt bunch are ridiculously weird in all sorts of respects, and their genomes are jumbled beyond recognition. So… not so great if you want to learn anything about our ancestors.