…and this is a 
No, not really — my title is a bit of a sensationalistic exploitation of the thesis of a paper by Peterson, Dietrich, and McPeek, but I can buy into their idea that microRNAs (miRNAs) may have contributed to the pattern of metazoan phylogenies we see now. It's actually a thought-provoking concept, especially to someone who favors the evo-devo view of animal evolution. And actually, the question it answers is why we haven't had thousands of Cambrian explosions.
In case you haven't been keeping up, miRNAs are a hot topic in molecular genetics: they are short (21-23 nucleotides) pieces of single stranded RNA that are not translated into protein, but have their effect by binding to other strands of messenger RNA (mRNA) to which they complement, effectively down-regulating expression of that messenger. They play an important role in regulating the levels of expression of other genes.
One role for miRNAs seems to be to act as a kind of biological buffer, working to limit the range of effective message that can be operating in the cell at any one time. Some experiments that have knocked out specific miRNAs have had a very interesting effect: the range of expressed phenotypes for the targeted message gene increases. The presence or absence of miRNA doesn't actually generate a novel phenotype, it simply fine-tunes what other genes do — and without miRNA, some genes become sloppy in their expression.
This talk of buffering expression immediately swivels a developmental biologist's mind to another term: canalization. Canalization is a process that leads organisms to produce similar phenotypes despite variations in genotype or the environment (within limits, of course). Development is a fairly robust process that overcomes genetic variations and external events to yield a moderately consistent outcome — I can raise fish embryos at 20°C or at 30°C, and despite differences in the overall rate of growth, the resultant adult fish are indistinguishable. This is also true of populations in evolution: stasis is the norm, morphologies don't swing too widely generation after generation, but still, we can get some rapid (geologically speaking) shifts, as if forms are switching between a couple of stable nodes of attraction.
Where the Cambrian comes into this is that it is the greatest example of a flowering of new forms, which then all began diverging down different evolutionary tracks. The curious thing isn't their appearance — there is evidence of a diversity of forms before the Cambrian, bacteria had been flourishing for a few billion years, etc., and what happened 500 million years ago is that the forms became visible in the fossil record with the evolution of hard body parts — but that these phyla established body plans that they were then locked into, to varying degrees, right up to the modern day. What the authors are proposing is that miRNAs might be part of the explanation for why these lineages were subsequently channeled into discrete morphological pathways, each distinct from the other as chordates and arthropods and echinoderms and molluscs.
The authors offer up three lines of argument in support of their idea. The first is the weakest, I think, because it relies on interpretation of some somewhat fuzzy fossil evidence. What they suggest is that if increasing canalization would be expected of phyla over evolutionary time, then early groups ought to show more variation within a species than later groups. We don't have a record of the actual miRNAs, you see, but a less canalized phenotype would be a visible effect of less tightly buffered developmental processes.
In one study measuring intra-specific variation in trilobites, that's what was found: the Cambrian trilobites were 'sloppier', with a wider array of different body forms within a single species, than Devonian trilobites.
Webster's quantification that polymorphisms, and hence phenotypic plasticity, decreases through geologic time. Shown is the temporal pattern of relative proportion of trilobite species coded as polymorphic in at least one character. Insufficient data reflect time bins where less than 40 species were available for analysis.
The second line of evidence is the one I thought most interesting. It's a mathematical argument built on the premise that a major function of miRNAs is to reduce noise in development and therefore reduce the amount of variation in the phenotype, when then has the superficially contradictory effect of increasing the ability of selection to promote specific variations.
The argument goes like this. We're interested in the amount of change in a particular trait over time, Δz. Δz is the product of the selection differential, S, and the narrow-sense heritability of the trait, h2. That last parameter is the key one: the phenotype is the result of additive genetic variation (VA), which is what evolution is selecting for, and the total phenotypic variance (VP), which is all the environmental pressures and internal random noise and various factors, including non-heritable elements, that contribute to the phenotype.
The heritability, h2, is measured as VA / VP…so reducing VP increases h2, which makes Δz larger for the same selection coefficient.
I know…that's a smear of symbols. Let's illustrate it graphically.
Imagine you have a population with 3 alleles, a1, a2, and a3, that affect some quantitative trait — let's say it is antenna size in an insect. Inheriting allele a1 gives the insect a small antenna, allele a3 produces a large antenna, and a2 is intermediate in size.
However, the alleles exhibit variation in the degree of expression. The a3 allele tends to produce larger antennae, but it isn't a hard and fixed size: some a3 insects have antennae no larger than the largest a1 insects. This is the situation illustrated in T0 of the diagram below — three alleles, each with a fairly wide phenotypic outcome.
Now look at T1, though: an individual has acquired an miRNA that buffers the expression of its a gene, in this case the a3 allele. It produces an antenna size that is right at the peak of the a3 distribution, and does it more precisely, producing fewer small antennae and fewer very large antennae. It makes the output of the a gene more reliable, but doesn't change the average size at all.
General scenario for the evolution of miRNA regulation. Imagine at T0 some polygenic phenotypic trait with low correspon- dence between the trait value expressed by individuals and the alleles they possess in their genotypes. At T1 mutations in an expressed RNA hairpin produces an allele that will bind to the 30 UTR of the key gene and thus stabilize the level of the gene product in an individual in the population. This mutation will spread to individuals with other alleles (T2), but will only slightly decrease the unpredictability of the trait values produced in the entire population because it is only present in a small fraction of the population (T2 and T3). Natural selection can now act by favoring individuals with alleles of the coding gene conferring higher fitness and with the regulator y miRNA allele (T3 and T10).
At T2, the miRNA has begun to spread through the population independently of the a alleles, so other insects with the a1 and a2 alleles have acquired it. Again, it doesn't change the average size generated by the a gene, but it does fine tune it, so the progeny of those individuals carrying the miRNA will more reliably resemble their parents.
The final panels illustrate what happens if there is selection for the larger phenotype. Without the miRNA, the distributions of the products of the a gene are mushy and broad; selection for large antenna size will act against some carriers of a3 and for some carriers of a1 and a2. The change in the proportions of the carriers, Δz, will be fairly small. With the miRNA, though, there is less overlap, and Δz will be greater even if the strength of selection for that particular phenotype is no greater.
Basically, the presence of a buffering system that reduces the phenotypic variability produced by a given allele makes the property relatively more heritable, and increases the selective evolvability of the organism.
Their first argument is indirect, estimating an increase in miRNA constraints from morphological data; their second is theoretical, suggesting that in principle accumulating more miRNA to canalize animal form should make selection more effective; and the third is an obvious one, to ask whether there is any direct molecular evidence showing that lineages have acquired increasing amounts of miRNA over evolutionary time. To answer that, they dug into the databases to see if they can find a pattern of addition of new miRNA families to various animal lineages, and it turns out there is some convincing evidence that that hasa been going on. In the diagram below, the little boxes contain numbers that indicate the number of new miRNA gene families added since the previous node. It looks like all of us, with the exception of one group of sponges, have been busily stockpiling new miRNAs throughout our histories.
(Click for larger image)
The acquisition of miRNA gene families from the Cryogenian (light blue), through the Cenozoic (dark yellow) for 24 metazoan taxa. miRNA family gains are shown at each node. Note that each node is characterized by the addition of at least one new miRNA family, and all eumetazoan lineages acquire at least one novel miRNA family. Further, there are three instances of a relatively high rate of miRNA family acquisition, once at the base of the protostomes and deuterostomes, once at the base of the vertebrates, and once at the base of primates (human and macaca). The only lineage not known to have evolved new miRNAs over the last 450 million years is the demosponge A. queenslandica.
This is a provocative idea, and I rather like it. It relies a bit heavily on the premise that the primary role of miRNAs is to simply stabilize patterns of gene expression, which may not hold up as we learn more about them, and it's also very much in the hypothesis stage right now, but it does propose an answer to a good question. It doesn't really say why we had a Cambrian explosion in the first place, but it does give a possible explanation for why we didn't have explosion after explosion, with each phylum blossoming into a wild riot of new body plans and radical morphological changes at frequent points in their histories. It may be because they gradually evolved mechanisms to increase the reliability of multicellular developmental processes.
Peterson KJ, Dietrich MR, McPeek MA (2009) MicroRNAs and metazoan macroevolution: insights into canalization, complexity, and the Cambrian explosion. BioEssays 31:736-747.
Life Science
Comments
Posted by: Calypte | July 15, 2009 5:16 PM
"morphologies don't swing too widely generation after generation"
Creationists have been claiming this all along.
Posted by: Glen Davidson
|
July 15, 2009 5:17 PM
Very interesting.
On the picky and decidedly secondary point of language, though, saying that miRNA "caused" the Cambrian "explosion" immediately begs the question of the cause behind miRNA changes.
More likely is that the cause was, at least in part, increased oxygen levels, and miRNAs facilitated adaptation in response to that and other changes.
I do say that with a mind to criticisms from IDiots, etc.
Anyway, thanks for the info, and it sounds credible.
Glen D
http://tinyurl.com/mxaa3p
Posted by: LRA | July 15, 2009 5:22 PM
We used to call miRNA RNAi.
Posted by: Athena Andreadis | July 15, 2009 5:26 PM
MiRNAs and alternative splicing: the two fine-tuners and major contributors to proteomic complexity!
Posted by: Stu
|
July 15, 2009 5:30 PM
Wait a minute, this post does not exist: this is not a science blog! They said so over at the Intersection.
Posted by: SC, OM | July 15, 2009 5:31 PM
That's very interesting.
Posted by: Dutch Delight | July 15, 2009 5:34 PM
"morphologies don't swing too widely generation after generation"
Creationists have been claiming this all along.
And now you want a cookie for being right about something we apparently already agree on?
Posted by: Blake Stacey
|
July 15, 2009 5:39 PM
Actually, Young-Earth Creationists have claimed that morphologies diversify wildly in a very small number of generations. . . right after Noah's Flood. That's how millions of living species could come from the limited number of "kinds" represented on the Ark.
Posted by: Blake Stacey
|
July 15, 2009 5:44 PM
Although why we're talking about creationist mindbarf instead of genuine science. . . sigh.
Mad propz to P-Zed for actually including mathematical symbols in this one. See, even biologists could use LaTeX support!
Posted by: Jadehawk, OM
|
July 15, 2009 5:46 PM
all this "fine tuning" talk is bound to attract either the creobots or the experience/telos nuts; or both :-/
anyway, this is fascinating: a great example of complexity of the basic building-blocks of life building up through natural selection. you start out with a simple and vague general thingy, and through generations of differentiated procreation rates, you get extra layers of active agents, so now you have a multi-agent system that does very specific things. and all without magic.
nature is fascinating. this is one of those moments I wish I had enough money to go back to school.
Posted by: Platypus | July 15, 2009 5:58 PM
LRA @ #3:
RNAi (RNA interference) is the process by which small antisense RNA molecules can silence some genes, whereas miRNAs are the actual small antisense RNA molecules.
Posted by: jimmiraybob | July 15, 2009 5:59 PM
What caused the Cambrian explosion?
Geologically speaking I think it was tied into Noah's Snowball* [queue up the research wing at the AIG Noachian Snowball Research Institute of Subverting Scientific Inquiry].
See here for a completely biased secular humanist interpretation.
* when the Lord commanded Noah to build an igloo and then to shelter 2 of each kind and the Lord froze the Earth over for 40 days and nights... or a year... or something. And then when the snow and ice melted there was a loud explosion and life also exploded and all the excess melt water went underground for later use (see Flood). Sheesh, I thought this was a science blog.
Posted by: Nerd of Redhead, OM
|
July 15, 2009 6:00 PM
Yummy hard science. Very interesting concept.
Posted by: Cappy | July 15, 2009 6:08 PM
"morphologies don't swing too widely generation after generation"
Maybe not, but after the ten thousandth generation or so you start to see some differences.
Posted by: genesgalore | July 15, 2009 6:09 PM
change the composition of the atmosphere: and a whole bunch of prior niches fail as well as new possibilities open. once a niche is occupied, it's not easy extracting the occupant.
Posted by: ThorSonofOdin
|
July 15, 2009 6:13 PM
I've shown that my favorite protein - MeCP2 can bind non-specifically to RNA. I often wonder whether microRNA can somehow modulate the secondary structure formation of MeCP2 and in turn control chromatin architecture - transcriptional access. Someone will make a nice chapter of a thesis that no one will ever read out of that question someday if not with MeCP2 then with soe otehr chromatin architectural protein. oh how I love Chromatin. Or Chrrrrromatin as Karolin would say.
Posted by: Happy Tentacles
|
July 15, 2009 6:19 PM
Good serious thought-provoking science.
But how long will it take before someone misinterprets it as supporting their particular brand of woo?
Posted by: Aristide Valentin, Chief of the Paris Police | July 15, 2009 6:26 PM
Wait a minute! I understood that!
I spend far too much time on ScienceBlogs...
Posted by: Jennifer B. Phillips (aka Danio) | July 15, 2009 6:28 PM
miRNAs are an example of one of those humbling scientific wake-up calls wherein we all shake our heads in wonder at how little we actually understand about the genome. I remember being quite giddy with anticipation when I first learned that you can actually knock these things down with morpholinos (and, of course, overexpress them as well). Ridiculously cool stuff.
Oh, and, just wondering:
How many people reading this would never have known about miRNAs if PZ hadn't blogged about it today?
Posted by: oaksterdam | July 15, 2009 6:37 PM
*raises hand*
Posted by: Kite | July 15, 2009 6:39 PM
Another terrific explanation of an important current scientific topic- your clarity always makes me envy your students. Also a breath of fresh air, needed (by me at least) to clear the smog of the recent flame-wars (which I am guilty of enjoying a little too much).
Posted by: 'Tis Himself
|
July 15, 2009 6:45 PM
You can't makes posts like this, PZ. You're explaining science to the non-specialist and Mooney says you don't do that.
P.S. Thanks for the post. It was clear and understandable to this non-scientist.
Posted by: AndrewTheEternal | July 15, 2009 6:46 PM
@19
~De-lurks to raise hand
~Scurries back to lurking hole
Posted by: truthspeaker | July 15, 2009 6:48 PM
I'm just posting here to confirm that I do, in fact, read and enjoy the science posts, even if I rarely have much to say about them.
Posted by: Bob L | July 15, 2009 6:56 PM
If this is true interesting to think what has happening before MRNA layed down the law. Lineages wildly diverging in a few generations?
Posted by: Neil | July 15, 2009 6:56 PM
I figure this is a good post to ask, and I know there are many of you that can answer this for me. What exactly is evo-devo entailing? I was a biology major in college so I know the underlying concepts of evolution but have not really kept up on the latest evolution advances. I am assuming evo-devo is a combination of evolution and development? can anyone explain a little better? Thanks!
Posted by: Mr.Man | July 15, 2009 7:01 PM
Yeah, PZ never EVERS blogs about science.
Cool stuff.
Posted by: Sili
|
July 15, 2009 7:02 PM
I don't know how you find the time for this, PeeZed.
But thank you. I have learnt more biology here than I did in A-levels (Of course, back then I didn't pay attention) and first year uni (ditto).
Posted by: Darren Garrison | July 15, 2009 7:02 PM
Another in the list of speculative, hard-to-prove "cause for the Cambrian explosion" is outlined in this book (came out a few years ago, but I only came across a copy last year):
http://www.amazon.com/Blink-Eye-Vision-Sparked-Evolution/dp/0465054382
I don't know if the arguments and conclusions are any more solid than any of the other attempts to explain the Cambrian explosion, but it is an interesting read, especially since you can pick up a used copy for a pittance.
Posted by: Dania
|
July 15, 2009 7:04 PM
Thanks for the well written post, PZ.
It's a very interesting idea, indeed. Thought-provoking and exciting I would say. Now I'm just curious to see how well it holds up as we learn more...
Posted by: Jesse | July 15, 2009 7:05 PM
Keep in mind...........that the Cambrian "explosion" isn't necessarily a biological process. There is a lot of evidence to support the fact that the preservation potential of the ocean floor changed during the Cambrian, allowing for already living groups to become preserved. In other words, no "explosion". I think molecular clocks agree with this viewpoint.
Posted by: Rob | July 15, 2009 7:16 PM
Again @3,
just a bit more on RNAi, it is usually referred to as the result of therapy induced by the RISC (RNA induced Silencing Complex) I Say therapy because it generally refers to a treatment or experiment... i.e. RNAi is used to create knockout mice more cheaply than GM + Breeding which can take a while and cost a lot - RNAi is accomplished by supplying the cells with siRNA --> which is basically exactly the same as miRNA but siRNA (short interfering) is scientist-supplied.
Posted by: Peter Beattie | July 15, 2009 7:24 PM
I realize this is entirely off-topic, but am I the only one thinking, 'When is the last time Chris Mooney's blog had something about real science?' Can we at least now tell him to shut up already about how PZ and Pharyngula are counterproductive? Please?
Posted by: amphiox | July 15, 2009 7:33 PM
"morphologies don't swing too widely generation
after generation"
Creationists have been claiming this all along.
One had hardly merit points for "claiming" this. It's a self-evidence observation, that can, and has, been made in real time.
Ye who have eyes to see, behold! (And even among the creationists, a very small, but vocal, minority is capable of this)
Posted by: Religion™ Brand Brain Staples | July 15, 2009 7:43 PM
That's amazing.
No, seriously. I did a verrry small amount of work in Genetic Programming as a graduate student, and one of the things we took for granted was a tight coupling between genotype and phenotype.
Now, I was aware at the time that this isn't strictly true for biological systems (neutral/silent mutations, for example), but I never considered at the time that even the level of genotype->phenotype coupling we see today was something that had to evolve too.
Posted by: genesgalore | July 15, 2009 7:46 PM
i waiting for the day when the miRNA-o-matic spits out the appropriate encapsulated nucleotide chain to swirl in my dinner wine to keep those cancer tumors away.
Posted by: Jon D. Moulton | July 15, 2009 7:46 PM
@Jennifer B. Phillips (aka Danio): Me too. I remember first hearing that Morpholinos could be microinjected into embryos, knockdown a gene and still allow development to proceed. Suddenly, I felt I might have a job for a while.
As for knocking down miRNAs, I found Wigard Kloosterman's paper where he reported it works (data not shown):
Kloosterman WP, Wienholds E, Ketting RF, Plasterk RH. Substrate requirements for let-7 function in the developing zebrafish embryo. Nucleic Acids Res. 2004 Dec 07;32(21):6284-91.
I emailed Wigard and suggested he try to block Drosha and Dicer activity, which led to this:
Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RHA. Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol. 2007;5(8): e203.
Since then, I've been delighted by the appearance of every Morpholino-miRNA paper.
Posted by: Jon D. Moulton | July 15, 2009 7:50 PM
@Rob: The main difference between siRNA and miRNA is that cells have evolved with miRNA present. Short (~20-23 base) dsRNA is classified as micro-RNA (miRNA) or small interfering RNA (siRNA) depending on whether it is endogenous or introduced from outside the cell.
Organisms have evolved with their miRNA present, with small changes in miRNA sequence throughout the history of the vertebrates. An miRNA affects the expression of many genes, but the cell has evolved with these effects; if the miRNA gene modulation is deleterious for survival through reproduction it is selected against, while if it is overall beneficial to propagation it is selected for. The genes modulated by the miRNA have themselves been subject to mutation and selection, in particular of the sequences where miRNAs bind and have their effect, the microRNA response elements. Thus an miRNA can affect the expression of many genes without toxicity -- indeed the miRNA is required for the proper regulation of the expression of many genes.
siRNA, introduced by an experimenter, also alters the expression of many genes. However, lacking selection over evolutionary time, these off-target effects are for the most part deleterious. Investigators modulating gene expression with siRNA are generally trying to knock down expression of a single experimental target without altering the expression of other genes, but it is known that the expressions of hundreds of genes are modulated when a single siRNA is introduced. Without the vetting of evolution, an siRNA will have toxic effects in animal cells and teratogenic effects in embryos. While siRNA have been touted as potential therapeutics, they are far from a magic bullet. Rather, they resemble a hand grenade, with a single siRNA modulating splicing, transcription and expression of many genes along with induction of innate immune responses. As an innate biological system, miRNAs are a beautiful genetic control network. As a technology for targeted gene knockdown and as a potential therapeutic, siRNA has serious flaws.
Posted by: not a gator | July 15, 2009 7:56 PM
Great article, and I really appreciate the graph provided with argument 2. (My eyes were actually glazing over when I saw the graph, and it all suddenly made sense. I do realize that there are those whose eyes, conversely, would glaze over at the sight of the graph.)
I was confused by your intro paragraph. Let me see if I understood correctly. It seems that if this mechanism for regulating phenotype expression exists, it increases the action of selection pressures on specific genes, thus resulting in less variation between individuals in a population group and, I would assume, a faster rate (as measured in years) of allele change in populations experiencing changes in environment. Without this mechanism enforcing homeostatis (right word?) then the impact of subtly altered genes is much lower.
In other words, if MiRNA is this mechanism, then it serves to make any organism (breeding populations, not individuals, natch) that has it more competitive over time (multiple generations).
Depending on what you mean by explosion, I suppose you are trying to say that the presence of this mechanism in modern organisms makes them much quicker to react to and adapt to changes in the environment (including fitting themselves neatly into niches, as Darwin's finches do) and thus they would outcompete the ungainly "monsters" of the Cambrian seas.
In other words, the Cambrian was early in the game and a lot of weak sisters got by. Now the rules have changed--it's a jungle out there.
If that's what you mean, then I agree. :D
And again, fascinating article.
Posted by: not a gator | July 15, 2009 8:07 PM
@38
So, in other words, if the process of evolution were a software programmer, it would be the arrogant, sloppy sort of programmer prone to reusing variables in multiple modules and patching scraps of code onto other scraps of code when they ought to be cleanly separated and reusing old programs written for entirely different functions (and probably buggy until a narrow set of inputs are given) in order to get the job turned in by deadline?
Posted by: Religion™ Brand Brain Staples | July 15, 2009 8:22 PM
@40
You just described why maintaining legacy code is a nightmare. But that is a whole other can of worms. (And I'd have gone with feckless instead of arrogant, but that's just me ;^_^)
Posted by: Malcolm | July 15, 2009 8:25 PM
Jennifer B. Phillips (aka Danio)@19
*raises hand*
Posted by: Tommy Traddles | July 15, 2009 8:45 PM
"
In case you haven't been keeping up, miRNAs are a hot topic in molecular genetics:"
But they're old news...
"Proc Natl Acad Sci U S A. 2009 Jul 1. [Epub ahead of print]
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.
Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL.
The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142;
We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to approximately 3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC)2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that approximately 20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression."
I think you would have to be brain-dead or totally disingenuous to attribute this level of organization to random mutation and natural selection.
Posted by: Jamie | July 15, 2009 8:52 PM
@19
/raises hand
Although I haven't thought about miRNA much since graduating last year.
Posted by: John Atkeson | July 15, 2009 9:06 PM
In other words, the Cambrian was early in the game and a lot of weak sisters got by. Now the rules have changed--it's a jungle out there.
One really interesting thing about this proposition is to wonder what would have happened if MiRNA had happened much later, and life continued its random(er) walk more millions of years before the big 'tightening up'?
Could there have been islands of yet weirder, but viable morphologies out there that our current nichiness prevents us from ever reaching today?
We need more planets to look at!
Posted by: kamaka | July 15, 2009 9:54 PM
Neil @ 26
The short answer: Much can be learned about the workings of evolution by observing the process of embryonic development in diverse organisms.
See "Endless Forms Most Beautiful" by Sean B. Carrol.
Great book.
Posted by: Ken Wilber fan | July 15, 2009 10:33 PM
Very interesting stuff, PZ. Evo-Devo is a promising paradigm filling in gaps where neo-Darwinism leaves room.
Neil @ 26 and Kamaka @ 46,
Another up and coming paradigm is Developmental Systems Theory, which like Evo-Devo (though arguably in a more radical way) challenges the standard Darwinian (random mutation and natural selection alone) approach.
http://en.wikipedia.org/wiki/Developmental_systems_theory
Posted by: John Morales | July 15, 2009 10:36 PM
<raises hand> This was news to me too.
--
not a gator @39,
I'm one of those for whom equations are easier to grasp than graphical representations.
Posted by: David Wilford | July 15, 2009 10:42 PM
"Basically, the presence of a buffering system that reduces the phenotypic variability produced by a given allele makes the property relatively more heritable, and increases the selective evolvability of the organism."
Thank you PZ for summing up so clearly and concisely the thrust of this research. I should come back here more often than I have lately!
Posted by: John Morales | July 15, 2009 10:43 PM
Ken, this is a science post, your integral theories don't belong here. Save them for the open threads, please.
Posted by: Mickey Mortimer | July 15, 2009 10:46 PM
Interesting, but is there really a diversity-causing event to explain in the first place? Kimberella suggests mollusk-like animals were present in the Precambrian, and burrows show bilaterians existed then too. As you state, the Cambrian explosion is remarkable mostly because so many taxa start to preserve hard parts. Yet the body plans must have existed before this, so isn't it more likely the emergence of modern body plans was gradual? Also, can we really talk about a time in which different lineages were "locked into" a body plan? I know Gould loved the idea, but it seems to me every new lineage is "locked into" its own plan to the same degree, whether it be a new phylum or a new genus. What's to say Arthropoda is a more distinguishable body plan than Deuterostomia? And what of taxa like the parasitic barnacle Sacculina? In what sense is it still locked into the arthropod body plan?
Posted by: Ken Wilber fan | July 15, 2009 10:46 PM
What does DST have to do with integral theory?
Posted by: John Morales | July 15, 2009 10:50 PM
Neil @26, PZ has a number of posts on evo-devo, accessible through the search box at the upper left.
For example, this one: Evo-devo in 60 seconds.
Posted by: Nerd of Redhead, OM
|
July 15, 2009 10:59 PM
Fan Boi, open thread, which is found here. Philosophize until your heats content.
Posted by: djlactin | July 15, 2009 11:09 PM
I'm dubious. Morphological diversity actually began increasing millions of years before the so-called 'explosion', so the lineages ancestral to extant phyla were probably already in place by the Cambrian. The cambrian event was simply an increase in fossilization rates (related to adoption of hard parts) and (If i recall correctly) an increase in size in many lineages) Two questions follow:
Why did these changes wait until the Cambrian to happen?
Why did they happen "simultaneously" in so many lineages?
(Inquiring minds want to know.)
Here, the hypothesis is that miRNA began reducing phenological variability more or less simultaneously in many lineages. This raises the question: how did it begin doing so among a large array of pre-existing lineages? Discounting the hypothesis that it originated concurrently in all lineages on the eve of the explosion, I see two possibilities.
(1) It was already present in all lineages, having been passed down from a deep common ancestor. This should be the null hypothesis, I think. But if it is correct, we need to explain why the miRNA began exerting its effect quasi-simultaneously among all lineages.
(2) It originated in one lineage (during or just preceding the Cambrian) and was transferred to the others. This requires actual transfer of the relevant bits of DNA. Viruses can cause transfection like this, so it's not out of the question, but such wide-spread effect requires postulating a global cross-taxon epizootic. IMO, this scenario is hard to believe.
I lean toward scenario (1), but even if (2) is valid, two questions follow.
Why did these changes wait until the Cambrian to happen?
Why did they happen "simultaneously" in so many lineages?
These are the same questions that have been asked for decades. The proposal just adds another possible explanation but no answers.
IMO, this hypothesis is no better than the "increasing oxygen levels" hypothesis; and is perhaps weaker, because it requires a more complex mechanism.
Posted by: Jennifer B. Phillips (aka Danio) | July 16, 2009 12:48 AM
djlactin,
it seems like a lot of your questions could be answered by figure 3 (the tree):
They didn't. They happened before, and they happened after within different lineages at different times. Interestingly, though, our bilaterian (preCambrian) ancestor seems to have stockpiled a whole bunch of them prior to the protostome/deuterostome split, hence the suggestion that having so many of these modifiers to work with at once contributed to the subsequent 'explosion'. A couple of other high-volume acquisitions are also noted in the figure legend, both of which precede periods of heightened diversification. The same can be said of Hox genes. It's a pretty well established phenomenon that if you add more tools to the kit, they will be picked up and used in a variety of new and different ways.*
*please note that this analogy in no way implies actual tools, nor any sentient, directed wielding thereof.
Posted by: Intelligent Designer | July 16, 2009 2:44 AM
Are miRNA generally derived from introns?
Posted by: Grendels Dad
|
July 16, 2009 3:24 AM
Slightly OT, (or at best tangential, the Cambrian explosion appears to figure prominently in this question)
Has anyone read Richard Leakey’s The Sixth Extinction? I picked it up at a used bookstore a while back and have just gotten around to looking at it. The first couple of chapters don’t seem too promising.
Posted by: Sigmund | July 16, 2009 3:39 AM
I work with microRNAs in my particular field of research (cancer genetics). From an evolutionary point of view microRNAs are very interesting since they illustrate an important point. If an organism has a functioning microRNA processing pathway - which consists of a series of proteins that recognize RNA folded into a hairpin looped structure, cleaves it and then incorporates part of this sequence in an antisense regulatory RNA protein complex that targets mRNAs with the complementary (opposite) sequence - it then has the ability to rapidly acquire new regulatory microRNAs. Any mutation in a transcribed sequence that results in a new hairpin loop will potentially result in an entirely new microRNA!
In contrast new regulatory proteins take much longer to develop since they are so much more complicated and require much more mutations, gene duplications, translocation/fusion etc.
This means that new ways to regulate the same set of protein encoding genes can be developed much faster in the presence of microRNA pathways than in the absence. I suppose one possible consequence of this is the ability of the organism to develop complex tissue specific structures - multicellular life as we know it, from basically a very similar number of proteins to unicellular organisms.
Posted by: Rolf Massoff | July 16, 2009 5:54 AM
Tommy @ 43: 200 years ago, all it took to trigger the
'you-must-be-brain-dead-not-to-see-the-evidence-for-
the-creator's-hand' response was pitching your foot
against a pocket watch while walking upon the heath.
The threshold has been raised considerably.
Posted by: Andreas Johansson | July 16, 2009 6:36 AM
Not really - the highest numbers of additions (all at n=84, oddly) are at the base of the mammals, base of the primates, and on the branch leading to Branchiostoma (amphioxus), only the first of which could be said to exhibit particularly heighened diversification. In particular, it's noteworthy that the rodents (Mus and Rattus in the graph) have much fewer additions than the primates, yet are massively more diverse.Posted by: Ranson | July 16, 2009 7:45 AM
*Raises hand*
It was in the most recent Smithsonian magazine.
Posted by: AdamK | July 16, 2009 9:00 AM
@19
*raises hand, fingers a-waggling*
Posted by: Ian | July 16, 2009 9:34 AM
What caused the Cambrian explosion? It was eco-terrorists - and look at the planetary pollution they caused! I can't believe you guys don't know this....
Posted by: nn | July 16, 2009 9:44 AM
(without having read the paper)
My understanding was that according to the molecular studies
all the major lineages in the Cambrian had already diverged
much earlier (i.e. humans and flys are diverging for far
longer than 650mil years)
What's unclear to me is how a single mechanism should have spread
to all these different lineages who do not interbred at all?
They would have needed to all evolve it independently?
Or does mRNA depend on some environmental factor that could
have changed at that time?
Posted by: NiK0 | July 16, 2009 10:14 AM
Ascertainment bias? Looks like there's more changes reconstructed at the common ancestors of popular model organisms than anywhere else. Perhaps if we understood more about miRNA families in non-model organisms we'd observe them more often.
Posted by: Lynna | July 16, 2009 10:23 AM
Sounds like chaos within specified boundaries to me. Is there a chaos theory component?
Posted by: Lynna | July 16, 2009 10:49 AM
Apart from Tommy @43, have creationists seized on this as evidence for their "hey, it could happen in 6000 years!" arguments?
Posted by: Mike | July 16, 2009 12:26 PM
*Raises hand @19*
What a cool idea. Thanks for explaining this PZ.
Posted by: Ivar Husa
|
July 16, 2009 1:36 PM
Thanks for the knowledge passed along, PZ. Excellent post. You are an educator, first and foremost, though I do appreciate your godless ejaculations as much.
Posted by: jhuguru | July 16, 2009 2:19 PM
@57
microRNA primary transcripts are pretty diverse in structure, and many are quite large (many kb). They are generally capped, spliced, and poly-adenylated just like other PolII-transcribed genes. microRNAs can be generated both from exonic and intronic portions of the transcript.
There is, also, a really interesting class of microRNAs known as "miRtrons" where the pre-microRNA is an entire intron. Thus, the splicing machinery itself generates a pre-microRNA which is then processed by Dicer to yield a mature miRNA. These miRtrons are thereby able to bypass the general need for Drosha processing in the nucleus.
Posted by: jhuguru | July 16, 2009 2:21 PM
@57
microRNA primary transcripts are pretty diverse in structure, and many are quite large (many kb). They are generally capped, spliced, and poly-adenylated just like other PolII-transcribed genes. microRNAs can be generated both from exonic and intronic portions of the transcript.
There is, also, a really interesting class of microRNAs known as "miRtrons" where the pre-microRNA is an entire intron. Thus, the splicing machinery itself generates a pre-microRNA which is then processed by Dicer to yield a mature miRNA. These miRtrons are thereby able to bypass the general need for Drosha processing in the nucleus.
Posted by: frog | July 16, 2009 2:44 PM
Hmm, something seems to be missing in this idea that miRNA's reduce noise by down-regulating translation. There's got to be something more to it than that -- "down regulation" wouldn't have much effect on noise. Limiting the differentials of up & down regulation is what limits noise.
Noise is the tendency to up and down spike -- not the tendency to have high or low levels of a signal. If anything, high-levels will mask noise (if it's a DC noise), by making it relatively smaller.
Am I missing the argument, or is the argument missing a crucial point? Maybe the argument is that by capping levels, the systemic behavior of interacting control systems is less noisy -- but how would you show that in general?
Or maybe since the mRNA absolute levels are equivalent to the first derivative of protein levels, by capping them one source of noise in protein levels is reduced? But that seems just as likely to produce noise by filtering on part of the feedback loops between proteins and protein production.
I'm just not sure how you can make a general argument about functionality like that.
Posted by: jhuguru | July 16, 2009 2:46 PM
@68
It's not entirely clear to me that the de novo evolution of microRNAs would be all that trivial. The specific sequences needed for a primary miRNA's transcript to be processed by Drosha/DGCR8, exported to the cytoplasm, processed again by Dicer, and loaded into RISC constitute a pretty specific set of structural constraints. For example, when people have attempted to replace specific bits of sequence in endogenous microRNAs (in order to make novel engineered silencing molecules), these constructs often don't express very efficiently compared to the original miRNA. Likewise, it can be challenging to take siRNAs that work well and turn them into hairpins (so called shRNAs) that work like endogenous microRNAs. It seems that, in addition to the miRNA-target pairs themselves, small RNAs have also evolved substantially to be efficiently processed by our cellular machinery.
Furthermore, protein evolution by duplication/divergence or the aquisition or loss of cis- regulatory sequences can be pretty rapid (on the evolutionary scale, anyway).
Posted by: DynamicUno | July 16, 2009 4:09 PM
First off, I struggled through the math bit as best I could, but my eyes had started to glaze over in defeat RIGHT when he admitted it was a slew of symbols and launched into an explanation that made it perfectly clear. So thanks for that.
I'm interested in seeing more on this - it seems hard to believe that the sole purpose of miRNA is to regulate phenotype expression ranges, I think it's fairly reasonable to expect additional (and perhaps a primary) purpose from them with increased research. Though I admit I don't really have any idea what they could be.
Posted by: Anonymous | July 18, 2009 10:14 AM
Holy crap, that was interesting. I just wish I knew the molecular mechanism of miRNA's role in decreasing phenotypic variance. Is it already known or still under research?
Where can I find more about it?