Tag Archives: SRP

The SRP, Alu Elements, and Nudging


I’ve combined the essays about the signal recognition partcle, Alu elements, cytosine deamination, all connected by front-loading. All 11, 465 words of it.
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Insp. Bunny Interview Part 3

report2We’re back.  Inspector Bunny, you said that the SRP was an elegant system that would go on to influence evolution.  Can you expand on that?

matrix3 Sure.  A key component of the SRP is one of the domains that is part of the RNA component, known as the Alu domain.  This Alu domain is not needed for life to exist, given the fact that most bacterial SRPs don’t have it.  But some do have it.  And interestingly enough, those bacterial versions of the SRP look more like the human Alu domain than other protozoan domains.  In other words, in some bacteria, the SRP is needlessly complex for survival, but appears to be needed for the subsequent evolution of more complex states.

report2How so?

matrix3 Well, first of all, bacterial don’t need the Alu domain because they don’t need to pause ribosomal synthesis.  The cells are so small that they can hook up the ribosome to the membrane protein channel while the gene is in the very process of being expressed.  But in the much larger eukaryotic cell, whose cytoplasm is cut off from the DNA by the nuclear membrane, the pause function is needed. And it is the Alu domain that serves as the core component for delivering this pause function.  In other words, some bacteria contain an SRP that would function as one preadaptation that would nudge evolution toward the emergence of the eukaryotic cell, a cell plan that would be needed to evolve a complex animal state.

report2 Oh, so you are saying the Alu domain that is part of the RNA component of the SRP is there to facilitate evolution?

matrix3 Sure.  I’m saying we can perceive things like this and there is nothing to say we would be wrong.  From there, we would find example after example of other preadaptations, all converging on the same nudge.

report2 Such as?

matrix3 Oh, that is a whole set of other features found in various bacteria.  We’ll get to some of those eventually, but let’s instead notice that the SRP is apparently not finished in guiding subsequent evolution.

report2 So you are saying there is more to the SRP story than being an elegant system that not only solves a core problem for life, but also facilitates the evolution of the complex eukaryotic state?

matrix3Well done, One with Glasses.  Billions of years after the origin of eukaryotes, fast-forward to the evolutionary emergence of primates.  If primates had not evolved, humans could not have evolved.  Something very interesting happened very early in primate evolution.  The sequence for the Alu domain was copied and duplicated and gave birth to a new retrotransposon – the Alu element.

report2 What’s that?

matrix3 Think of a retrotransposon as a device that can make copies of itself and spread throughout the entire genome.  If you are a duck, you’ll see it as some selfish parasite and yawn.  But we bunnies, while understanding how the ducks see it, also see a deeper meaning – it is a mechanism to reformat entire genomes.  That is, it is a mechanism to enhance and facilitate evolution.  Remember, the blind watchmaker is completely at the mercy of the variability that life hands it.  These Alu elements set about reshaping the genome, offering the blind watchmaker a vastly larger array of options to edit.  And during primate evolution, these Alu elements were busy trying out different reformatting solutions for brain development.

report2 So the SRP then ultimately played a role in the evolution of the human brain?

matrix3 Yeah, a big role.  In fact, without the Alu elements, he have no reason to think the human brain would have evolved.  What’s more, without retrotransposons, we have no reason to think the human brain could have evolved.

Earlier, I mentioned that all designers are constrained by the available design material.  Since the blind watchmaker is a designer-mimic, and its design material is largely protein, then we need to ask just what could the blind watchmaker actually make without proteins?  Would it still be able to produce a world like the one that exists?

Well, here we see the same theme, but in this case, it is not design material, it is design strategies that are available.  The Alu elements allow for the possibility of massive and relatively speedy reformatting and adaptation.  Could the blind watchmaker have sculpted something like a human brain without this mechanism being available?

report2 I see.  So you are saying that the blind watchmaker will always do what the blind watchmaker does – cull available variability according to some fitness test.  But that because of the SRP, the blind watchmaker has more options to work with.

matrix3Sure.  What’s more, some of those options will always sit there in-waiting, knowing that sooner or later the blind watchmaker is bound to call upon them.  It’s just a matter of time.  And once called on, they can help steer and guide the blind watchmaker, causing something remarkable to emerge on the stage that in turn will add further guidance when it comes to future available options.

Y’see, this Alu story gets even more interesting.

report2 Tell us.

matrix3Well, I’ve run out of time and need to return to all that inspecting right away.

report2Okay, Inspector Bunny.  Thanks for talking with us.  We’ll be sure to follow your next hare-brained installment.

matrix3 Thank you.

daffyThis is all so dessspicable!

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Insp. Bunny Interview Part 2

report2 Okay, we’re back.  Inspector Rabbit was about to talk about the signal recognition particle.

matrix3Yes, I was pointing out how, on several levels, life is built around these internal tensions, where one need is being played against another need.  Then, at the very interface of these tensions, we find solutions that are remarkably elegant and ingenious.  The SRP extends this theme of elegance.

report2How so?

matrix3 Here you have this relatively simple system, composed of three parts, that not only solves the problem of building life around lipid membranes and proteins, but also carries out multiple complex functions.  Imagine you are a muscle cell and need some more insulin receptors in your membrane.  Okay, so you express the insulin receptor genes and start translating this genetic information into a receptor.  When the first part of the receptor under construction is made, it carries a pattern of amino acids that function as a signal, in effect saying, “Hey! I belong in the membrane.”  It is the SRP that scans for this very signal.  When it finds it, it binds to that signal and it is this binding which then triggers the other elements of the SRP to put the ribosome in pause mode.  The SRP then helps the ribosome dock to a membrane tunnel in which it can resume protein synthesis.  This tunnel will then facilitate the insertion of the insulin receptor into the membrane.

report2 Oh, so you are saying it is so complex it must have been designed?

matrix3 No, no, no.  We’re not talking about what must have been designed, as I don’t know of anything that must have been designed.  And we’re talking about a relatively simple system.  This is not an example of a complex mix of parts giving rise to a simple function.  This is a simple mix of special parts that give rise to multiple functions needed for life.  That’s elegance.

report2Yeah, but elegance is a subjective call.

matrix3 As are most calls.  Yet keep in mind that I didn’t invent this assessment.  Those who work with the SRP on a daily basis are impressed with its elegance.  And what’s more, the system is so elegant that we can rather easily deconstruct the system in terms of its function. It can be reverse engineered.  This deconstruction helps us to see that the PAUSE step can be skipped without collapsing the functional network, an important consideration when it comes to the difference between prokaryotic and eukaryotic cell plans.

report2 So you are saying this system is so elegant it could not have come into existence without design?

matrix3 No. I am focused on gathering clues and following up hunches.  I’m Inspector Bunny, not Peter Gappin Cottontail.  And built into the core of life is a simple, elegant system that radiates rationality. You can bask in it.  It is, of course, possible that the blind watchmaker strung it together, yet the signature feature of the blind watchmaker is the kluge.

report2 Kluge?  Isn’t he a Swedish actor?

matrix3 Funny, One With Glasses.  A kluge is  some messy conglomerate that just happens to get the job done in any way that it can.  Throw some junk at the wall and whatever sticks, go with it.  If the blind watchmaker cobbled the SRP together, it was a rather lucky blind watchmaker.

report2 How so?

matrix3 Not only did a kluge-making mechanism stumble upon an elegant solution, it was so elegant that billions of years of constant subsequent tinkering could not find a better solution anywhere.  When you’re coming up with a solution to a problem off the top of your head that not only works, but works such that no one else can come up with a better solution after billions of years of looking, you are one lucky inventor.

report2But natural selection is not about luck!  Dr. Dawkins tells us this all the time.

matrix3 Yes, but luck does comes into play when relying material that happens to be laying around.  Luck does come into play when getting the solution right from the very beginning.  Either it’s extraordinary luck, or someone has been rigging the whole game.  But it doesn’t stop with this ancient, universal, elegant device.  It turns out this SRP would come in very, very handy when it comes to other evolutionary events much later on.  So much so that we might say evolution would have produced a rather mundane living world without it’s lucky find.

report2 Hold that thought, Inspector Bunny.  As we need to take another commercial break.  We’ll be back with Inspector Bunny and the Luck of the Blind Watchmaker.

Insp. Bunny Interview

report2Hey people!  I’m here with Inspector Bunny, who is well known for annoying ducks with all his constant digging of rabbit holes. Inspector Bunny, would you mind describing your latest rabbit hole?

matrix3 No problem.  We began with a core tension that is built into the fabric of life itself.  The themes of Compartmentalization and Adaptability are universal in life.  Compartmentalization is needed to sequester the machinery of life from the environment, but this machinery cannot be completely cut-off, otherwise it would not be able to help life adapt to the challenges posed by a changing environment.  The perfect solution to this dilemma is the membrane composed of lipids and proteins.  The lipid bilayer serves the needs of Compartmentalization while the embedded protein sensors, channels, and pumps  serve the needs of Adaptability.  Thus, the membrane, composed of lipids and proteins, is universal in life.

report2So are you saying the membrane must have been designed?  Because, like, it’s so darn complex??

matrix3Silly reporter. No, don’t get side-tracked by such questions.  The truly remarkable image comes from focusing on the elegance of the system, not from what must have happened or could not have happened.

report2 Okay, so focus on the elegance of the system.

matrix3The membrane itself is truly elegant, both structurally and conceptually, but it itself comes with its own built in tension.  All proteins are stitched together, one amino acid at a time, by the nanotech machines known as ribosomes.  When the newly formed proteins emerge from the exit tunnel of the ribosome, they fold into conformations that are essential for their function.  But because the cytoplasm of the cell is mostly water,  the proteins fold in such a way that the oily amino acids are mostly buried in the central core of each protein, forming the conformational back-bone of the protein. The surface of the proteins is decorated with amino acids that can interact with the surrounding water molecules.

report2 So?

matrix3Well, this poses a very serious problem for the proteins embedded in the membrane, or any protein trying to get across a membrane.  The lipid bilayer is a very different environment than the watery cytoplasm and repels those dissolved, folded proteins whose surface amino acids are complexed with water.  That’s why it so perfectly satisfies the needs of Compartmentalization, as anything, including proteins, dissolved in water can’t get through the lipid bilayer.  So how do you get protein sensors or channels in the membrane when the membrane is supposed to keep proteins, among other things, from getting across it!?  You simply take the proteins that are supposed to be in the membrane and turn them inside out, so the oily residues are on the surface and find themselves quite at home in the oily layer of membranous lipid.

report2Okay, so how do you turn a protein inside out?

matrix3The structure of any protein is determined by its amino acid sequence.  So all you would need to do is string together various amino acids in a sequence that would cause the protein to fold inside-out….if it was in an oily environment.  And there’s the catch.

report2 Oh, I think I get it now.  The ribosome does not make proteins inside membranes.  It exists inside the watery cytoplasm. So if the ribosome made membrane proteins inside the cell, the proteins could not fold properly.

matrix3Yes, and what’s worse, these unfolded membrane proteins would end up existing as gobs of oily goo.  And when goo bumps into other goo, it becomes a growing goo that will gunk up the whole cell.

report2 Sounds icky.  So what keeps the goo away?

matrix3 That’s where the signal recognition particle  hops in!  The signal recognition particle, or SRP, extends the theme of elegance as it…..

report2 Hold that hare-brained thought Inspector, as we need to take a commercial break.    Don’t go away folks, when we come back, the Inspector will tell us all about this SRP thingy.

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No rest for the SRP

matrix2Earlier in the summer, I pointed to a study that shows evidence of genome reformatting during human evolution:

In new research the Leeds team reports that a protein known as REST plays a central role in switching specific genes on and off, thereby determining how specific traits develop in offspring.

The study shows that REST controls the process by which proteins are made, following the instructions encoded in genes. It also reveals that while REST regulates a core set of genes in all vertebrates, it has also evolved to work with a greater number of genes specific to mammals, in particular in the brain – potentially playing a leading role in the evolution of our intelligence.


Says lead researcher Dr Ian Wood of the University’s Faculty of Biological Sciences: “This is the first study of the human genome to look at REST in such detail and compare the specific genes it regulates in different species. We’ve found that it works by binding to specific genetic sequences and repressing or enhancing the expression of genes associated with these sequences.

“Scientists have believed for many years that differences in the way genes are expressed into functional proteins is what differentiates one species from another and drives evolutionary change – but no-one has been able to prove it until now.”


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The Distant Potential of Front-loading

The reach of the Alu domain may have extended much further into the future that the evolution of eukaryotes.  Shortly after the dawn of the primate lineage, the gene for the SRP RNA was duplicated and the Alu domain was freed of its SRP function.  A second round of duplication occurred and the two Alu domains were merged to form what is now known as the Alu element [55].

The Alu elements have played an important role in the evolution of the primate genome.  Since escaping from its SRP function, the number of Alu elements has expanded to 1.1 million copies in the human genome, making up 11% of human DNA [56].  Since Alu elements do not code for any protein, they were once considered a classic example of “junk DNA.”  In reality, they are retrotransposons.  A retrotransposon is a gene that is transcribed into RNA and an enzyme known as reverse transcriptase uses it to make a DNA copy that can be inserted some other place in the genome.  Since the Alu element does not code for reverse transcriptase, where does the enzyme come from?  When the Alu elements were born early in the primate lineages, they commandeered the reverse transcriptase from an older retransposon in the genome known as L1.

What is the purpose of spreading all these Alu elements around during the dawn of human evolution?

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Found a nice animation of the SRP in action:

Pause in Waiting

In the previous posting, I asked which state is more like the ancestral state – the eukaryotic system with its larger RNA molecule, Alu domain, and SRP9/14 proteins or the bacterial system with its smaller RNA molecule lacking an Alu domains and the SRP9/14 proteins?

Consider the secondary structure of the SRP RNA from mammals and E.coli*.  Here is the complex mammalian RNA:


and here is the much simplified E. coli RNA, where the entire left half (the Alu domain) is missing:


So which is more like the ancestral state?

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Connecting to the Future

The trickiest part in the Design Matrix is to detect the echoes of foresight.  In the Design Matrix: A Consilience of Clues, we sketched out two possible ways of recognizing foresight.  One way is to look for molecular machines that exhibited Original Mature Design (OMD).  What we would have is machine that appears abruptly in the biotic landscape and then is not significantly improved or changed after extensive subsequent evolution.  In other words, the designer got it right from the start.  OMD can be viewed as an echo of foresight because there is no reason to think the blind watchmaker would have a decent chance of getting things right from the beginning.  When the blind watchmaker cobbles something together through cooption, it doesn’t know what it’s producing and is only “solving” the immediate problem at hand.   And there is no reason to think a solution to an immediate problem would just happen to work, much as is, billions of years later.  A rational mind, on the other hand, can see beyond the immediate state and contemplate how something might need to be constructed in light of possible future contingencies.

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Particle Protein and Friends

To really appreciate the beauty of the SRP system, we should look more closely at the major players.  But first, let’s make things more manageable.  Lucky for us, the bacterium E. coli has a scaled-down version of the system that nevertheless functions much like the system seen in human cells [8].  The RNA is much smaller, being only 114 nucleotides in length and thus lacking the Alu domain [9].  Furthermore, instead of having six different proteins as part of the SRP, the E. coli version has only one, known as Ffh.  Since there is only one, we’ll just call Ffh the ‘particle protein.’  E. coli also has the receptor (FtsY) and the translocon (SecY).  Thus, the system is actually quite simple, being composed of a small RNA molecule (4.5S RNA) that is bound by the particle protein which in turn binds to the receptor and the translocon.

Let’s first put the particle protein under the microscope.

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