Specification of what? It seems that in this case you are only judging it against a known design that you recognize (not the process of design itself - which ID has not determined or defined).

That is, you say it hasn't distinguished itself apart from its process, but this is exactly what evolution is.  So, again, how do you determine that life "appears designed" when you have nothing in the process to point to as outside of its natural progression?

I'll try to answer most of issues together.


Hm.... So what is a "new" binding site. I would say that a non exposed region is not a binding site as nothing can bind to it and it is not under selection pressure for any kind of binding. It a newly exposed region has something to bind it it is a new previously non existing binding site, subject to a new previously non existing selection pressure.


In so closely related species as human and chimp most changes are in the affinity (a lot of examples in "fine tuning" of gene expression), simply because time from divergence has not been long enough to make a big leap. Given the time available, there is no way that in one of these two an insertion of about 150 bp (which would code 50 amino acid (aa in the rest of the text) long section, a reasonable length for a new binding domain) would accumulate trough mutations. As you mentioned, mutation rate is about 1 per 100,000 base pairs, estimates for eucariotes are somewhere in that order, or even 1 per 1 000 000, per generation. But consider that insertion is a less likely event than nucleotide substitution, that less than 2% of genome is protein coding, a third of mutations in coding regions are silent because of redundancy of genetic code and a majority of mutations don't get fixed in population. That a new section of one gene coding a totally new binding site (not duplication, not changed, not duplicated and changed) would appear in such a short time... no, I can't find a specific example of that.

For genes involved in basic metabolic pathways and, any new domain is unlikely. Example: human myoglobin (154 amino acids) differs from sperm whale myoglobin in 25 aa, and in 88 when compared with shark myoglobin. Now 500 million years separates humans from sharks and still our myoglobin has no new binding domain in spite of aa changes. Selection pressure, myoglobin has a job to do. There is a twist in myoglobin evolution which I will explain later.

Now the genes that are subject to more quicker evolution are those involved in "fine tuning", that is regulation of DNA expression, in immune system and cell to cell communication. A typical genes from this group are usually code proteins with names something like:

• [insert name of protein]-like protein
• hypothetical protein, similar to [insert name of protein]
• cell surface receptor/antigen
• [a name for a short DNA sequence]box binding protein

and so on. In this type of genes, a minor change in aa sequence can change the pattern of protein-protein and protein-DNA reaction. Protein-DNA interaction can be followed with several variants of microarray experiments where changes in expressions are monitored across thousands of genes spotted on a small piece of glass. Small changes in aa result for example in 200 genes to be upregulated, 200 genes to be downregulated. Protein-protein interactions and how they are changed are not studied beyond individual cases, because there are no cheap systems available to monitor them. There was a total protein-protein interaction map done on S. cerevisiae (yeast), but they only have 3000 or so proteins. Human 20000 or so genes code several times of that proteins, that further modify each other in mature forms. So one would have to check binding of 1 protein against at last 1 000 000 other proteins. Not possible with current technology.

New protein-protein interactions via new binding sites (totally new, not just changed affinity) are monitored only trough comparing some more researched enzymes of distant organisms. A classic example is DNA polymerase. In procariotes, it is very simple, in eucariotes, it binds with a bunch of other proteins (activators, inhibitors, helicases, gyrases....). So here you are, totally new binding sites on the DNA polymerase core protein evolved to interact with other proteins.

Of course, such a distant comparison is problematic, as it can only deal with proteins available in both organisms and because of great differences in generation time in both organisms. Currently, there are not a lot of organisms between mammals and procariotes with finished genome sequences (I can think of chicken, 2 fishes and fruit fly - hm, is it still the only invertebrate?). Comparisons between them and human has only recently begun.

To avoid distant species and different generation time, a detailed globin family study was done to monitor "evolution in progress" as my Biochemistry book by Mathews & van Holde says. Now euchariotes have much lower rate of mutations than procariotes and longer generation times (E. coli - about half an hour, human - 20 years or so). So most evolution in eucariotes was done by small changes with big consequences in gene expression (see microarrays experiments) or by duplications of individual domains (like transmembrane chains, kinase domains...) or duplications of whole genes. This duplications have the advantage that from the pair can maintain previous function, while the other can evolve with no fear of strong negative selection pressure. Exon-intron organisation of eucariote genes seem to enable such domain duplications, while mobile elements like transposones can copy paste section of genes or whole genes. When monitoring evolution of such a gene in a single species, generation time and mutation rate is a constant.

So, gene coding ancestral globin diverged trough gene duplication 800 million years ago (estimates obtained when comparing organisms that diverged previously) in myoglobin and hemoglobin. Myoglobine can is a single chain protein holding one heme group. Hemoglobin evolved further as 500 million years ago when it was duplicated into alpha and beta chains. These developed new binding domains that enabled them to form a 2-alpha chains, 2 beta chains and 4 heme groups protein. These binding domains are not present in myoglobine that is incapable of binding with other globins. But most of differences in genes/proteins in human (at least 9 functioning globin variants and a bunch of fast evolving pseudogenes) is in affinities, time of expression of globin and tissue where it is expressed. This is where diversity of higher organisms, like mammals, comes from.

Please avoid this term.


Mutation causing sickle cell anaemia is not breaking current function (transport of O2) or destroying orderly operation. It is a new adaptation in host to pathogen relation and is currently under positive selection pressure.


I don't understand. Please rephrase the question.

That would be me (full of it). It was my subject line.

Inherent as in intrinsic.  You find fault with my word choice?


I am surprised you deny that sickle cell anemia represents broken and reduced operation.  Part of fit for purpose operation is the systems ability to co-exist with wider operation.  In the case of sickle cell, the defective protein (it is considered a defect) results in collapse of the normal red blood cell shape causing the spleen to interpret that the cell is damaged and target it for destruction, thus the anemia.  Surly you agree that those with this condition are impaired.

However as  you indicate, the sickle cell trait is an excellent example of what evolutionary processes are capable of accomplishing.  In the process of reducing (breaking) functional capability of the red blood cell system, this trait also provides a degree of protection from the malaria parasite by disrupting its life-cycle.  When those who have one sickle globin gene and one normal globin gene, oxygen carrying capacity is reduced slightly but the cell does not collapse to the same extent and the spleen does not destroy the cell.  However when malaria is present in the cell, it is much more easily damaged and also collapses so that the spleen now targets infected cells while preserving the relatively more healthy cells.   Once again this is an example of evolution breaking or damaging normal function in order to preferentially target a larger threat that is applying selection pressure.  Note that genetic studies in America and Europe indicate that where the pathogen is removed, this weaker trait, no longer be selectable, is in decline verses more functional globin.  There is no indication of a permanent path forward.  What is interesting is that there are numerous other mutations with similar effect (various forms of thalesemia) that also cause a weakened infected blood cell also preferentially destroyed.  Each one of these is also considered a defect, et each also makes malaria more survivable.  None of them show any sign of further progression.  None of them show any ability to become better at fighting off malaria.  More to the point, it is this accident which involves damaging function that has proven valuable in surviving malaria and yet the system in our body who's purpose is to identify and eliminate pathogens has proven useless and incapable of evolving any functional defense against malaria.

Returning to the primary point, this example is not in the same class as the well fitted protein-protein binding interactions we observe throughout molecular biology.  I urge you once again to have a look at what we actually observe in biological systems.  Protonic NanoMachine Project from Japan Science and Technology Corporation


I'm sorry for the confusion.  Can you find an example where a binding site is exposed and the modified protein is used in a structure similar to the flagellum or cilium systems described in the link? 

RF said:


I would be interested in any identified design process or event.

Can you provide an example of a new binding site anywhere throughout the entire span of organisms?  If we include your hemoglobin example (I will return to that one) I know of two.  The second is FKBP.  But a typical cell includes about 10,000 binding sites.  The FKBP example is also one of binding with itself when a substitution at position 36 causes the protein to bind to itself with moderate strength (about 100 times more strongly than sickle hemoglobin).  In a paper by C. T. Rollins and a host of others, in 2000 Proceedings of the National Academy of Science - USA , they make the strong point that this is unprecedented and appears to be the reversion of a previous mutation now being undone so strong is the affinity and natural is the fit.  It was as if the protein was engineered for the fit created.


Fit for purpose prevents change over time indeed.  This similarity could be common descent as you presuppose or it could be reuse of intentionaly designed components.



Isn't this just an excuse?  It sounds like the complaint, "I just need more time to find the missing processes and new interactions".  The reality is that we have studied or had the opportunity to study 10^30 organisms to uncover new binding sites and we have not found any good examples of a new one like the 10,000 we find in each cell.  But by the odds and compared to the rate at which these interaction need to be occurring in order to account for diversity by evolutionary processes, we should have discovered several thousands by now.