Monday, December 5, 2016

Dennis Venema, Galileo, and Protein-Protein Binding

Don’t Count on the Duchess

We have looked at Dennis Venema’s articles on evidences for common descent here, here, here, here, here, and here. In a recent discussion with Venema, he made the erroneous claim that the mammalian immune system, with its search for, and production of, antibodies, is a good example of why evolving protein-protein binding sequences is not a problem. In fact the mammalian immune system is yet another enormous problem for the theory of evolution. Furthermore, the mammalian immune system is not a good example because it is designed for this job of creating protein-protein binding sequences. It searches a well-defined design space extremely rapidly, and measures the success of its search experiments accurately and quickly. The fact that our immune system successfully designs antibodies in short order does nothing to address the problem of how random mutations occurring throughout the genome is supposed to have found myriad binding sequences, crucial for life. Venema also referred to another example which he has written about. Unfortunately this example also fails to demonstrate Venema’s claim of “evolution producing a new protein-protein binding event.”

The problem with evolving protein-protein binding is that too much gene sequence complexity is required to achieve the needed binding affinity. You could say it is an “all-or-none” type of problem.

One or two mutations will not generally do the job—you usually need more mutations before the two proteins stick together very well. And stick together they must, on a massive scale, in order to perform their necessary tasks. Even the simplest, unicellular, organisms contain massive protein machines, consisting of dozens of different proteins binding together to perform crucial life functions.

The study Venema referred to did a beautiful job in confirming this “all-or-none” character of protein-protein binding sequences. The study showed that in order for a viral protein to perform a relatively simple switch from one protein to a very similar protein required four types of mutations.

Anything less and no dice.

The twist in this study was that subsets of the four mutation types were apparently useful for a different function (strengthening the binding affinity to the original protein). So while in general the evolution of protein-protein binding sequences is astronomically difficult because too many simultaneous mutations are required, in this case the four mutation types could be accumulated, with useful benefit realized at some of the intermediate steps.

This is not a general result. It is not a revolutionary new finding that reverses our understanding of protein-protein binding sequences.

It confirms our knowledge, and adds a fascinating outlier case where the “all-or-none” character is circumvented by intermediate functions which, fortuitously “push” the design in the right direction. As the study explains:

The “all-or-none” epistasis among the four canonical phage mutations implies that it would have been unlikely for the new function to evolve on the scale of our experiments, except for the lucky fact that some of the mutations were beneficial to the phage in performing their current function, thereby pushing evolution toward the new function.

The study provides no indication that the untold thousands upon thousands of protein-protein binding problems in molecular biology would enjoy this type of setup. And if they did, oh what a most suspicious sign of design that would be.

Venema is mistaken in his failed attempt to recruit this study as a solution to the evolution of protein-protein binding sequences.

Strangely enough not only had Michael Behe provided his explanation of this study, but Venema was aware of it at the time of his writing. Venema explained that in his next article he would address Behe’s explanation, but in fact Venema simply rehashed Behe’s original explanation for why protein-protein binding is a problem for evolution.

Venema did not address Behe’s explanation but simply concluded that Behe’s original explanation must be false because, after all, this new study demonstrates the evolution of just such protein-protein binding sequences.

This is an unfortunate misrepresentation of a study that most readers will not understand. Venema completely misappropriated the study, and force-fit it into an evolutionary proof.

Additional problems

In addition to this basic problem of serendipity, this confirmation of the “all-or-none” character of protein-protein binding sequences was possible only with a very contrived, designed, laboratory experiment.

Simply put, a virus population was provided with a willing, and well fed host to live off of. In the meantime, many more host targets awaited the virus population. So a few mutations helped the virus’ infect the initial hosts, and mere single additional mutation then allowed the virus’ to infect the second group of hosts.

It was an entirely artificial, laboratory, environment, that wasn’t even intended to replicate a realistic evolutionary environment. Venema nowhere explained this.

Second, the study also discovered even more serendipity. Not only were there “luckily” intermediate fitness benefits, but the finding of the four mutations types also required certain mutations in the host genome.

Without them, no dice.

[Ed: Final section on the absence of synonymous substitutions removed, given the short timeline of the experiment.]


  1. Cornelius
    "measures the success of its search experiments accurately and quickly."

    Can you explain to me how this mechanism works?

  2. Folks might be interested in the back-and-forth between Cornelius and I over at the BioLogos Forum:

    1. Thanks from one lurker to Professor Venema for his many informative articles at BioLogos.

      I encourage readers here with doubts about evolutionary theory to take a look outside the echo chamber.

    2. LoL! Alan Fox is another evo who cannot find this alleged evolutionary theory. All he can do is reference darwin but darwin didn't posit a scientific theory. Alan doesn't know what science entails.

    3. Joey has surfaced and didn't see the theory of evolution. Six more weeks of winter.

    4. LoL! Wee Willy has choked and cannot link to the alleged theory of evolution. Many more years of lying...

  3. In local combinatorial search, constraints are a known problem. They make the landscape very rugged isolating islands (sometimes even points) from the rest of phase space and effectively blocking the search.

    Blind search has no hope in reality. Therefore there must be search guidance in some form. This is effectively demonstrated by ALL "genetic algorithms" without exception. Not everybody realizes though that GA model artificial selection, not natural selection!

    Non-point search algorithms can handle 'constraindness' better but non-point algorithms (like swarm optimization) assume the existence of communicating agents that share valuable information during search. We have no such assumptions in the Darwinian model.

    On average over all problems, there is no efficiency-dominant search algorithm that would be better than others (the so called 'no free lunch' theorem).

    This is why serendipity is elevated even further when co-evolutionary scenarios are seriously considered (serendipity squared :), where, allegedly, the 'no free lunch' theorem does not hold.

    There are terrible technical problems for something evolving in isolation. But when everything evolves at the same time, these problems strangely disappear...

  4. I am no expert in immunology, but doesn't our immune system develop new protein binding "solutions" all of the time? Are you suggesting that each one of these (billions on a daily basis) are the result of direct intervention? Or are you arguing that it is front end loaded? Which goes against your "not enough mutations" argument.

    1. No, immune sistem donot build new antibodies on early basis. You have the same number of antibodies today as the day you born.
      During the development your immune sistem produces a huge number of b linfocites each one with different immunoglobulines that will bind a huge number of posibles antigens. The ones that bind your own antigens are eliminated the others waits to enter in contact with an antigen with high binding constant.

  5. I would appreciate it if someone would post the link to the original article in Science? I'd like to make my own assessment.

    The podcast should also have this info.