Wednesday, September 06, 2006

System 3

The complement system.

For a biochemical switch to be useful you need

1. A mechanism to detect a change in the environment of a cell

2. An alternative action/pathway to switch to when the change is detected.


The switch on its own is no good if is doesn’t activate some kind of response to the change it detects.
The alternative "something to do" however is no use unless when it is needed you can switch it on. Usually the action to be switched on is a function which is needed only in certain conditions. Thus for it to work you need the switch and the function together. It is a logical "IF-THEN-ELSE" function. This is the central idea of Irreducible Complexity (IC) which Behe raised as a possible candidate for falsification of RMNS as the sole generator of biological complexity and as an indicator of intelligent design.



Switches (according to Behe) with their two alternative responses and some kind of detector system are therefore a good sign of intelligent design.

The complement system (as I understand it) is a system for blowing up cells. Blowing things to pieces is a dangerous job and needs to be handled by careful operators.

For an animal to obtain a system for blowing cells to pieces (bear in mind that an animal is made up of cells) is extraordinary.

To blow up a cell you only need to make a suitably sized hole in it. The rest happens as a matter of course.

Let us start from the position of having a fully functional cell blasting system which is triggered by molecules usually associated with bacteria detected by innate unchanging proteins sticking to carbohydrate molecules only found on the surface of bacteria. These are what I am calling the “dumb immigration officers.” The “dumb immigration officers” don’t do anything very clever they just look for sugar molecules with a foreign appearance and stick to them.

The switch in these systems is a switch between a “snipper” protein with a protective cover and a “snipper” protein that is going around snipping things.

The conversion to an active “snipper” is caused in the “dumb immigration officer” system by a protein complex sticking to certain sugar type molecules only found on bacteria surfaces.



See the molecules involved here.
The solution to the evolution of the “intelligence led immigration officer” system is that the same “snipper” switch (presumably by gene duplication and mutation) becomes activated by antibody which has stuck to a foreigner rather than by sticking to bits of the foreigner itself.

Behe asks whether it is reasonable to believe that this development of the cell blasting system together with the “intelligence led immigration officer” system can be explained by a gradual step by step process of incrementally increased function.

The problem with fiddling around with the binding site of one of these snippers is that you are fiddling around with explosives! The only binding sites that will be useful are those which are unique to foreigners….and if you get things wrong you have pressed the suicide button.

Is it reasonable to think of an organism experimenting with a duplicated "snipper" gene until it hits on a binding site that binds antibody stuck to a foreigner? My gut response is that this is not going to work but I suppose it depends on the frequency of useful binding sites as opposed to the lethal ones.

16 Comments:

Anonymous Hrafn said...

Andrew, whilst waiting for Matt & Ian to turn up to set you straight on the biological details, I thought I'd bring your attention to this piece.

Some of the more pertinant quotes:

"How to Become an Expert
...
Most experts don't stay in their original areas. They move into new fields. You get to be an expert in a new field by learning enough about it to be able to teach it and publish credible research in it. Experts don't just learn a subject, they learn how to become an expert. They learn how to find references, and understand them thoroughly enough to be able to duplicate that level of expertise in their own work."

You will note that Behe has neither "published credible research" in, nor taught, immunology, evolutionary biology, or any other field directly relevant to his claims, and thus cannot be considered (under Dutch's definition) to be an "expert" on these issues.

"Staying Expert
...
One reason university professors have to publish research is to ensure they stay expert in their fields.
...
As much as I despise the "publish or perish" system, the comments I got from people who never published research were horrifying. They either had not read a journal in years, or if they did read recent research, misunderstood it. Expertise in any field is truly a matter of "use it or lose it." Some of these people had lost the right to be considered experts."

You will note that Behe has published almost nothing in terms of scientific research in the last decade or more. He has not "used it," and is widely considered to have "lost it," and thus has little scientific credibility left.

5:05 pm  
Anonymous Matt Inlay said...

Andrew, I'm not sure I follow portions of your essay. I think there are several typos in the beginning, for example. Could you double check your writing and make sure there are no typos? I can't understand a lot of what you're trying to say.

When you've finished that, see if you can answer these 2 questions.

1. Are antibodies necessary for complement system function?

2. Can complement proteins aid the immune system without the function of "blowing cells up"?

If you need help, check out my article on the TalkDesign.org website:

http://talkdesign.org/cs/?q=evolving_immunity

3:23 am  
Blogger Andrew Rowell said...

Hmm.... Matt if you can't understand what I am talking about I think I better do a re-write rather than check for typos! I have put in a few inverted commas and split a sentence or two... but I will try a re-write when I have a spare few minutes. My interest was mainly in the switch system and the transition between an innate switch system to a system which can be activated both by the innate system and the adaptive system.

In answer to your Qs
1. No
2. Yes

11:39 am  
Anonymous Matt Inlay said...

Andrew, I'm still having a lot of trouble understanding your post. For instance, this is the first sentence:

"For a working switch you need two (or more) possible actions to switch between and the switch itself."

Is this grammically correct?

"My interest was mainly in the switch system and the transition between an innate switch system to a system which can be activated both by the innate system and the adaptive system."

The activation of the complement pathway by the adaptive immune system evolved much later than the complement system itself. While the origin of that activation pathway is interesting in-and-of itself, it really has no bearing on the issue of irreducible complexity. Clearly the antibody-mediated activation of complement system is reducible. Take away the antibody and the complement system can still be activated, can still function. I fear that by focusing on how complex each part of the immune system is, you're losing focus on the important issue, is the system irreducibly complex, and if so, is that a roadblock to it's evolution?

Now the complement system basically has two essential parts, the thioester motif, and the serine protease that activates the thioester motif. All other components are non-essential. In the most basic complement system, a serine protease is activated by a foreign infection, which turns on the thioester motif. Once activated, this thioester motif attaches to nearby proteins, both neutralizing the proteins, or opsonizing them. You might argue that the two components are both essential to the complement system, and you'd be right, but does that mean they couldn't have evolved. No, and the answer lies in the arthropods, which don't possess a complement system. They do have the thioester containing protein alpha-2-macroglobulin (a2M). This protein is activated by the serine proteases floating around in the hemolymph. These serine proteases have their own function completely independent of immunity. a2M functions as a protease inhibitor, shutting down the proteases, by binding to them (after a2M is activated) and neutralizing them. Again, it's not too difficult to imagine a pathway by which this system could have evolved. Simply put, a serine protease becomes attached to an innate receptor by the microevolutionary process of exon shuffling. With one simple step, an IC system is created.

10:07 pm  
Blogger Ian Musgrave said...

Hrafn Said whilst waiting for Matt & Ian
[Lurch voice] You rang [/Lurch voice]
Sorry I've been away, I've been marking essays, submitting papers, watch SMART-1 crash on the Moon, helping my son design a wind powered car and writing an essay for PT.

Catch you soon when I get some sleep (oh, and there is a Sky&Space deadline too, ug).

1:10 pm  
Blogger Paul (probably - maybe Liz) said...

"One simple step" can't make an "IC" system - by definition. If it only takes one simple step, then the system isn't IC. So presumably Matt fundamentally disagrees with the IC tag in the first place.

10:58 pm  
Blogger Andrew Rowell said...

Paul,
Matt I am sure does not believe that there are any IC systems. Certainly that is his argument regarding these three immune system examples. The IC in his concluding sentence I think should be in inverted commas.

10:21 am  
Blogger Andrew Rowell said...

Matt,

I see what you are saying.
The switch is contained within one molecule a2macroglobulin and can only be IC if one protein can be IC.

10:46 am  
Anonymous Matt Inlay said...

Paul (probably - maybe Liz) said...

"One simple step" can't make an "IC" system - by definition. If it only takes one simple step, then the system isn't IC. So presumably Matt fundamentally disagrees with the IC tag in the first place. "

You're referring to Behe's 2nd definition of IC, which is a system that requires one or more unselectable steps to evolve. This definition is ludicrous. If you accept this definition, then no IC biological systems have been identified, because there are none that can be shown to require one or more unselectable steps to evolve. Because you can never conclusively identify a system as IC according to this definition, it's totally useless. Furthermore, it's a completely different definition than the original definition of IC, so it shouldn't be given the same name (IC) that the original definition has. A more accurate name for that definition is "unevolvable". Essentially, what Behe is saying by using that 2nd definition is, "unevolvable" systems can't evolve. Most of us have decided to ignore that definition because of its uselessness in the debate.

The supposed novelty of Behe's original defintion of IC (multiple essential parts), is that it gave an empirical method to determine whether or not a system was IC (as opposed to the 2nd definition). That way, Behe could say that bacterial flagellum, adaptive immune system, blood-clotting cascade, etc. were irreducibly complex. However, as Andrew as just figured out for the complement system, just because a system is currently irreducible, that doesn't mean that it was always irreducible. The existing complement system requires at least two separate components, the thioester motif and the serine protease that activates it. However, the a2m protein contains the thioester motif, but uses serine proteases from other systems to activate itself. So while the current complement system requires 2 parts, the supposed ancestral system only required 1. This allows for the steady step by step addition of parts through simple "Darwinian" evolution, and is therefore totally evolvable.

6:36 pm  
Anonymous Matt Inlay said...

Andrew wrote:
"Matt I am sure does not believe that there are any IC systems."

If you accept Behe's first definition, then there are tons of IC biological systems. As I just mentioned, if you use his 2nd definition, then none have been thus far identified.

My point is that simple, non-controversial "Darwinian" evolution (random mutation + natural selection), can and does produce systems that can be empirically identified as irreducibly complex (meaning that they have multiple essential parts).

Since we have a very good idea of how a simple IC system can evolve, and since there's no qualitative difference between a simple IC system and one as complex as the flagellum, then there's really no reason to think that any IC system is unevolvable.

6:42 pm  
Blogger Andrew Rowell said...

Matt,

Can you tell me how you think a2M and proteins like it evolve?

9:26 pm  
Anonymous Matt Inlay said...

"Can you tell me how you think a2M and proteins like it evolve?"

I think Ian would be better at answering this, but I'll give it my best. I'm not entirely sure what you're asking here, but in terms of random mutation, there are a few different pathways by which a protein can evolve. The simplest is via point mutations due to errors in DNA replication. A point mutation here or there can change a proteins activity, its sensitivity to the environment, its interaction with other proteins, its specificity, and in rarer cases, its function entirely. Mutations outside of the coding region can change the expression patterns of the gene.

Aside from point mutations, another possibility is exon shuffling. This is due to recombination errors where entire exons or regions of a gene are copied or translocated to another gene. For example, if a transcription factor has a DNA binding region, and a transcriptional activation region, one of these two regions can move onto another gene, adding that particular function to the new gene. This kind of recombinational shuffling is non-controversial, in my opinion, as creationists often appeal to recombination as a means of evolution "within a kind". Additionally, if you believe Douglas Axe's work (or at least how Dembski interprets it), you might think that randomly attaching a chunk of a protein onto another protein will make the "fused" protein unstable. However, this is something observed both in nature (e.g. oncogenes in cancer), and in the laboratory (e.g. fusion proteins or tagged proteins) all the time. It works more than it doesn't work.

I hope that helps answer your question.

10:10 pm  
Blogger Andrew Rowell said...

Matt,

Regarding your suggestions for the evolution of a2m - Do they answer my question? Not really.

The problem I have in my mind is a protein which has a powerful (presently useful because carefully controlled) destructive function which only becomes active when the bait region is removed.

10:04 am  
Anonymous Matt Inlay said...

Andrew, I'm not sure why that's a problem for you, can you elaborate?

5:17 pm  
Blogger Andrew Rowell said...

Matt,

I suppose it is because A2M seems to have its basic function as destroying proteins (if I understand correctly) Thus it seems to need both that function and a means to control its action fairly carefully.
It also seems odd that an organism should find it selectively advantageous to have the protease function and then selectively advantageous to get rid of it.

11:25 am  
Anonymous Matt Inlay said...

by Andrew: "Thus it seems to need both that function and a means to control its action fairly carefully."

I think one misconception a lot of people have about the evolution of new systems is the need for regulation of that system. Most people think of a population of organisms, sitting around for a thousand years doing nothing, then one of them acquires a new system that gives it an edge over the others. It's important to remember that the environment that this population lives in isn't static, it's constantly changing, and the population needs to constantly adapt to those changes. If a brutal disease comes along that nearly destroys the population, than any of those organisms that have an increased resistance to that disease are going to have a better chance at survival, regardless of how poorly regulated that system is.

One example is the sickle-cell allele. As you probably know, individuals carrying the sickle-cell allele are more resistant to malaria than individuals with the wild-type allele. However, individuals homozygous for the sickle-cell allele are reproductive dead ends, and even those heterozygous have their own problems. Under normal circumstances anyone carrying the sickle-cell allele would be at a disadvantage. However, if malaria were to break out, then those carrying the allele would survive better than those without it. If malaria became so prevalent that there was no population that wasn't exposed to it, then maybe after a thousand years the ability to regulate the sickle-cell allele might evolve. Imagine if all this took place several hundred thousand years ago, and that because of RM+NS, the sickle-cell allele was only expressed in individuals that are currently fighting off a bout of malaria. If that happened, today we might all be sitting around wondering how the sickle-cell system could have evolved, given that the sickle-cell allele is so dangerous in the absence of malaria.

8:13 pm  

Post a Comment

<< Home