Are functional proteins rare?

[bob b]

I have now asked the most competent evolutionary minded people posting at TOL for their opinion regarding the rarity of functional proteins.

The reason for my request is of course obviously related to the claim that small changes to genes (and hence the proteins they code for) is how both microevolution and macroevolution operate.

The rarer functional proteins are the less credible the "random mutation plus natural selection" scenario becomes, particularly for so-called "macroevolution".

I genuinely want to hear about any proposals for solving what appears on the surface to be at least a "potential" problem for NeoDarwinism.

So far I have requested comments from Johnny, stratnerd, aharvey and ThePhy.

What do you think guys?

 

[death2impiety]

Expect a lot of "maybes" and "could haves".

They have no idea. You may as well ask them if they know what the Easter bunny does on Friday nights.

 

[Johnny]

Hi Bob. I have seen your inquiry and I am writing a response.

 

[bob b]

Hi Bob. I have seen your inquiry and I am writing a response.

Thanks, Johnny.

 

[bob b]

Johnny is working on a reply (see March 24th, 2006, 01:23 PM posting)

Harvey, stratnerd and ThePhy have yet to comment.

If functional proteins are rare does this doom "random mutations plus natural selection" as a feasible mechanism for macroevolution?

It well might.

 

[fool]

So far I have requested comments from Johnny, stratnerd, aharvey and ThePhy.

:noid:

 

[Shalom]

This will be good and at the very least extremely interesting to read. :up:

 

[Apologist]

If "functional" proteins were rare, i daresay most males would be very, very angry.

:rotfl:

 

[fool]

This will be good and at the very least extremely interesting to read. :up:

I'd be more interested if I was invited.
aharvey told us already he's got little time for TOL and I haven't seen Stratnerd around in a long time, and The Phy is a physicist. (I think Bob's afraid of the fool) :Zimster:

 

[bob b]

I'd be more interested if I was invited.
aharvey told us already he's got little time for TOL and I haven't seen Stratnerd around in a long time, and The Phy is a physicist. (I think Bob's afraid of the fool) :Zimster:

Don't be bashful.

Not to be disrespectful, but from the usual content of your postings I had assumed that you would have wanted to sit this one out and just snipe on the sidelines.

But if you think you are up to being serious for a change go ahead and enlighten us with your knowledge on this subject.

 

[fool]

OK.
"how rare are fuctional proteins"?
Obviously not that rare, I'm made outa em!
How's that?

 

[bob b]

OK.
"how rare are fuctional proteins"?
Obviously not that rare, I'm made outa em!
How's that?

About what I expected.

 

[fool]

About what I expected.

Just cause I don't write a long-winded answer with alota big words don't mean what i say ain't true. I just happen to have the gift of being able to come right to the point.

 

[eisenreich]

I hope Bob doesn't mind, but I posted his question on another forum under the title, YEC thinks he's found a smoking gun.. The board, Internet Infidels, has many posters that work directly in the fields of biology, chemistry, anthropolgy, etc (i.e., not simply hobbyist/enthusiasts). If Bob really wanted to have some of his questions answered, I'd encourage him to register on that board. Some responses:

The question may be about proteins which bear little resemblance to others - that have undergone many mutations from some other form to result in a rather unique amino acid sequence. The YEC is probably saying that if the protein only works in its deviated form, it's not plausible that it could have evolved one mutation at a time.

This isn't a problem. Suppose an organism makes a protein AAAAA, where the protein ABCDE performs some function with 100% effieciency. The intermediate forms AAAAB - ABCDD perform the same function, but at a lower effiency. Organisms with those forms would survive - until the lucky one mutates into ABCDE, gaining a significant advantage over others of its species. At that point, natural selection favors the ABCDE organism over all the others, and the intermediate forms die out.

Every time I hear this argument I keep going back to this paper. In this experiment a random sequence of DNA acquires a functional role in viral infectivity through mutation and selection.

J Mol Evol. 2003 Feb;56(2):162-8.

Can an arbitrary sequence evolve towards acquiring a biological function?

Hayashi Y, Sakata H, Makino Y, Urabe I, Yomo T.

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, 565-0871, Suita City, Osaka, Japan.

To explore the possibility that an arbitrary sequence can evolve towards acquiring functional role when fused with other pre-existing protein modules, we replaced the D2 domain of the fd-tet phage genome with the soluble random polypeptide RP3-42. The replacement yielded an fd-RP defective phage that is six-order magnitude lower infectivity than the wild-type fd-tet phage. The evolvability of RP3-42 was investigated through iterative mutation and selection. Each generation consists of a maximum of ten arbitrarily chosen clones, whereby the clone with highest infectivity was selected to be the parent clone of the generation that followed. The experimental evolution attested that, from an initial single random sequence, there will be selectable variation in a property of interest and that the property in question was able to improve over several generations. fd-7, the clone with highest infectivity at the end of the experimental evolution, showed a 240-fold increase in infectivity as compared to its origin, fd-RP. Analysis by phage ELISA using anti-M13 antibody and anti-T7 antibody revealed that about 37-fold increase in the infectivity of fd-7 was attributed to the changes in the molecular property of the single polypeptide that replaced the D2 domain of the g3p protein. This study therefore exemplifies the process of a random polypeptide generating a functional role in rejuvenating the infectivity of a defective bacteriophage when fused to some preexisting protein modules, indicating that an arbitrary sequence can evolve toward acquiring a functional role. Overall, this study could herald the conception of new perspective regarding primordial polypeptides in the field of molecular evolution.

In addition to Method's reference, see also Functional proteins from a random-sequence library
Quote:
Functional primordial proteins presumably originated from random sequences, but it is not known how frequently functional, or even folded, proteins occur in collections of random sequences. Here we have used in vitro selection of messenger RNA displayed proteins, in which each protein is covalently linked through its carboxy terminus to the 3' end of its encoding mRNA1, to sample a large number of distinct random sequences. Starting from a library of 6 times 1012 proteins each containing 80 contiguous random amino acids, we selected functional proteins by enriching for those that bind to ATP. This selection yielded four new ATP-binding proteins that appear to be unrelated to each other or to anything found in the current databases of biological proteins. The frequency of occurrence of functional proteins in random-sequence libraries appears to be similar to that observed for equivalent RNA libraries2, 3.

They aren't laying all over the place, but there are quite a few. See also the news brief, In vitromolecular evolution enters the stage of proteomics

Quote:
Using this approach, the authors constructed an mRNA-peptide display library of 6 × 1012 proteins each containing 80 random amino acids. (This is only a fraction of the theoretically possible sequence space of 2080 = 10104 protein species of that length.) Then, they selected for proteins that bind ATP over 18 selection and amplification rounds. Four families of ATP-binding proteins were found, which were unrelated to each other and did not show significant homology to any known biological proteins. Deletion analysis defined a core domain of 45 amino acids that was sufficient for ATP binding with a dissociation constant of up to 100 nM. Based on the occurrence of functional proteins recovered before mutagenesis, the authors estimate the frequency of functional proteins in the initial random library to be 1 in 1011.

As the experiments show, this frequency is sufficient to allow discovery of functional proteins in sequence space by a stochastic process, supporting current views on the origin of life. Conversely, the experimental success and the small fraction of sequence space occupied by functional proteins together tend to favor evolutionary approaches over de novo design in the development of novel proteins with therapeutic or industrial utility. The in vitro mRNA display of proteins provides a powerful experimental system for future investigation of the intricate interplay between chance, biological necessity and physical constraints in the evolution of proteins with more complex functions. (Bolding added)
In other words, while not laying on every street corner, biologically functional proteins are sufficiently common as to make using evolutionary mechanisms to find them more effective than designing them from scratch in human applications. Nature is no different.

 

[Johnny]

I just finished "researching" bob's problem. Checked out Behe's sources, etc. I should have my response typed out by the end of the week.

 

[bob b]

thank you eisenreich. I will discuss each point in separate postings.

This isn't a problem. Suppose an organism makes a protein AAAAA, where the protein ABCDE performs some function with 100% effieciency. The intermediate forms AAAAB - ABCDD perform the same function, but at a lower effiency. Organisms with those forms would survive - until the lucky one mutates into ABCDE, gaining a significant advantage over others of its species. At that point, natural selection favors the ABCDE organism over all the others, and the intermediate forms die out.

The author of this suggestion is merely restating what macroevolution assumes, namely that a lucky mutation will eventually find a functional protein which works more effectively than the one already existing in a working lifeform. This of course begs the question of the rarity of functional proteins, because if they are rare enough then what makes anyone think that a change in a single amino acid will ever find not only a functional protein, but one which is more effective than the one which already exists in a working lifeform?

This is easily seen in the limit, for if the set of functional proteins is F and the set of non-functional proteins is N, then assume that F/N = 10^-150. In this case it would be absurd to believe that one could ever find a new functional protein to replace the one already in place by using a random search strategy.

 

[bob b]

Case #2

J Mol Evol. 2003 Feb;56(2):162-8.

Can an arbitrary sequence evolve towards acquiring a biological function?
Hayashi Y, Sakata H, Makino Y, Urabe I, Yomo T.

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, 565-0871, Suita City, Osaka, Japan.

To explore the possibility that an arbitrary sequence can evolve towards acquiring functional role when fused with other pre-existing protein modules, we replaced the D2 domain of the fd-tet phage genome with the soluble random polypeptide RP3-42. The replacement yielded an fd-RP defective phage that is six-order magnitude lower infectivity than the wild-type fd-tet phage. The evolvability of RP3-42 was investigated through iterative mutation and selection. Each generation consists of a maximum of ten arbitrarily chosen clones, whereby the clone with highest infectivity was selected to be the parent clone of the generation that followed. The experimental evolution attested that, from an initial single random sequence, there will be selectable variation in a property of interest and that the property in question was able to improve over several generations. fd-7, the clone with highest infectivity at the end of the experimental evolution, showed a 240-fold increase in infectivity as compared to its origin, fd-RP. Analysis by phage ELISA using anti-M13 antibody and anti-T7 antibody revealed that about 37-fold increase in the infectivity of fd-7 was attributed to the changes in the molecular property of the single polypeptide that replaced the D2 domain of the g3p protein. This study therefore exemplifies the process of a random polypeptide generating a functional role in rejuvenating the infectivity of a defective bacteriophage when fused to some preexisting protein modules, indicating that an arbitrary sequence can evolve toward acquiring a functional role. Overall, this study could herald the conception of new perspective regarding primordial polypeptides in the field of molecular evolution.

-------------
This appears to be an experiment in artificial selection by an intelligent agent. They deliberately created a defective phage, and then improved upon the mutant by creating random changes to the defective section of the protein previously created. In other words in a real world environment the intermediate stages of their experimentally created phages would have tended to be eliminated by natural selection, because none of these stages were even close to being as effective as the wild type they started with.

However, this case might warrant further investigation, since they have selected one particular domain of a single protein, the one in question. The experiment may indicate what I have preciously mentioned might be possible, namely that families of certain functional proteins may exhibit a “clumping” phenomenon whereby small changes to an existing functional protein may be able to achieve a higher probability of success in achieving a new (better?) functional protein than the average when considering the entire available potential protein space. In practice such a phenomenon might possibly permit some degree of flexibility and hence permit organisms to adapt to changing environments (microevolution?), but would leave the question open regarding whether small changes can accumulate without limit and hence yield a credible mechanism for large changes (macroevolution).

 

[eisenreich]

Here are a few more from the same page, since you're ripping right through these. I could post your replies to the other forum for the appropriate rebuttals necessary for a debate, but it would be much easier for you to do so directly (depends what's more important to you, debate with people who may be more informed than you or continuing to post here and believing yourself to be superior on this board..)

Survival of the fittest is often misleading. For a mutation to be passed on, all that is required is that the mutation does not affect the organisms ability to breed that much. For instance, the vitamin C gene.

The problem here is that evolution is conceived differently by the creationist who sees evolution in terms of organisms becoming more complex by accumulation of novel protein-coding DNA. Hence they think small changes to existing genes is microevolution (adaption) and generation of new proteins and structures is macroevolution (speciation).

Creationists only seem to see life in the form of animals -- cat kind, horse kind and wolf kind being the favourites. Plants are hardly alive, microorganisms ignored completely and viruses definitely DEAD. So for them evolution consists of a series of impossible events such as sprouting wings for flight (a dinosaur lays an egg and a chicken hatches).

One can quote them laboratory experiments that demonstrate the production of novel proteins, but this falls on deaf ears. Indeed, considering population sizes and generation periods of higher animals (such as in cat, horses, and dogs) it is difficult to imagine how a new 'rare functional protein' could evolve.

The answer is that most functional proteins, enzyme systems and tissues (and the DNA that codes for them), were already evolved some 500 million years ago. The diversity of animal forms does not depend on new proteins, it is based more on the fine tuning and timing of action of already existing proteins during embryonic development.

I found this a revelation after reading Endess Forms Most Beautiful, although it is remarkable that the same basic tissues and biochemistry, developed by the time of the Cambrian, have served to create today's complex life forms without evolution having to 'go back to the drawing board'.

I must admit I despise the terms "Micro and Macro Evolution" because since the theory clearly requires that we all evolved from a common ancestor, these terms are misleading.

The answer to the original question posted by eisenreich is quite clear to me at least. The basic Creationist argument is that evolution reaches a certain point (usually defined as "kinds, but clearly confused, because there is virtually no agreement by different creationists as to the definition of a "kind"). Since most Creationists accept what they describe as "Microevolution", and do not accept "Macroevolution", it is up to them to provide a Scientific response to the question::

"What Scientific theory will allow evolution within a species, but prevent that species from evolving to the extent that it can no longer produce fertile offspring from it's former relatives?"

In simple terms, scientifically, why can evolution go from A to B, but not from A to C?.

I wish the terms [micro/macro] had never been invented. The creationist, who is normally only half educated in evolution, thinks they describe different processes. [replying to quote directly above] By a process in which mutations always leave the same or less information in the genome. This therefore imposes a limit to the number of branches on the baramin 'kind' tree and also gives rise to the genetic diseases found in dogs, for example. Macroevolution has to be dismissed, in their view, because it requires the evolution of 'new information', which is impossible.

 

[bob b]

The reason I don't go to other pages has several dimensions:

1) wolf pack phenomenon - I prefer to go with just a few opponents who are both well-informed and civil. Most websites like the ones mentioned gang up on a creationist and because the quality of the postings is so broad there is no way that a lone creationist can have a fruitful dialog there. Believe me I have tried.

2) this forum is special for me for reasons I prefer to avoid discussing publicly.

3) there is a possibility on this forum of altering the views of Christian "fencesitters".

 

[bob b]

Case#3

I must admit I despise the terms "Micro and Macro Evolution" because since the theory clearly requires that we all evolved from a common ancestor, these terms are misleading.

Yes they are. They both imply evolution (an increase in specified complexity) occurs.

The answer to the original question posted by eisenreich is quite clear to me at least. The basic Creationist argument is that evolution reaches a certain point (usually defined as "kinds, but clearly confused, because there is virtually no agreement by different creationists as to the definition of a "kind"). Since most Creationists accept what they describe as "Microevolution", and do not accept "Macroevolution", it is up to them to provide a Scientific response to the question::

"What Scientific theory will allow evolution within a species, but prevent that species from evolving to the extent that it can no longer produce fertile offspring from it's former relatives?" In simple terms, scientifically, why can evolution go from A to B, but not from A to C?.

Microevolution is really just sexual recombination and/or small horizontal or slightly deleterious changes. It can "mix things up" (recombination) or cause slight degradation (mutations) but it can't create anything completely new that wasn't already latent in the genome to start with.