Mutational Pathways

From: 'Creation Evolution Headlines'

http://www.creationsafaris.com/crev200604.htm

'Few Mutational Pathways Lead to Darwinian Evolution 04/12/2006'

"Mutations may not be as helpful for neo-Darwinian evolution as expected, say researchers from Harvard. Let’s say five mutations need to occur for a bacterium to gain resistance to an antibiotic, and there are 120 ways to get these mutations. They found that only about 10 of the pathways could be selected by natural selection. Since natural selection would have to confer better fitness at each step, most of the pathways are dead ends.

Although the team studied only one particular kind of resistance, “this finding likely applies to most protein evolution,” they said. “Although many mutational paths lead to favored variants, only a very small fraction are likely to result in continuously improved fitness and therefore be relevant to the process of natural selection.”

[Bradford]: This bears keeping in mind at a time when evolutionists seek to trace "ancestral proteins" by means of statistical techniques which reportedly can lead to the identification of the "original gene" related to a protein in question. Mutational paths must lead to an intermediate but if natural selection is to preserve favored variants these variants must not only improve fitness but do so at a level that makes the proliferation of the variant throughout a population inevitable. Then the process must repeat. We've witnessed proposed intermediate pathways, most notably to counter Behe's irreducible complexity concept, but fleshing out speculative pathways is another matter.

"Scientists reconstruct an ancestral protein by tracing its evolution into new versions carried by living species. Along each lineage, the gene for that protein picks up mutations, some of which alter the structure of the protein. Scientists can determine many of those mutations, and by working backwards up the evolutionary tree, they can determine what the original gene looked like. Thanks to powerful statistical techniques, they can determine how much confidence they can have in each letter in the genetic sequence they reconstruct. If they find a lot of statistical confidence in the overall sequence, they can then go to the lab and use it as a guide to build the corresponding protein."

"See also Science Daily, EurekAlert. The original paper was published in Science.1 The abstract states:

Five point mutations in a particular beta-lactamase allele jointly increase bacterial resistance to a clinically important antibiotic by a factor of 100,000. In principle, evolution to this high-resistance beta-lactamase might follow any of the 120 mutational trajectories linking these alleles. However, we demonstrate that 102 trajectories are inaccessible to Darwinian selection and that many of the remaining trajectories have negligible probabilities of realization, because four of these five mutations fail to increase drug resistance in some combinations. Pervasive biophysical pleiotropy [i.e., one modification causing a cascade of effects] within the beta-lactamase seems to be responsible, and because such pleiotropy appears to be a general property of missense mutations, we conclude that much protein evolution will be similarly constrained. This implies that the protein tape of life [sic] may be largely reproducible and even predictable. (Emphasis added in all quotes.)

The last sentence about what this implies is purely a speculation. They elaborate slightly in the last sentence of the paper: “It now appears that intramolecular interactions render many mutational trajectories selectively inaccessible, which implies that replaying the protein tape of life might be surprisingly repetitive. It remains to be seen whether intermolecular interactions similarly constrain Darwinian evolution at larger scales of biological organization.” If those larger scales are random and require multiple steps, it would seem the same principle applies."
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1Weinreich et al., “Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins,” Science, 7 April 2006: Vol. 312. no. 5770, pp. 111-114, DOI: 10.1126/science.1123539.

"It wasn’t going to work anyway, so this just makes it harder. They are’t talking about adding new genetic information or function, but rather losing function (susceptibility to the antiobiotic) in such a manner that each stage doesn’t kill all of the organisms in one fell swoop. If this principle applies, as they suggested, to larger scales of biological organization, then the neo-Darwinian gig is, for all practical purposes, over. Try getting a whale from a cow against these kinds of constraints. This makes “the protein tape of life” predictable? In whose Tinker Bell tale?"

[Bradford]: Natural selection is more a logical than an empirical device. Whether sufficient genetic possibilities are generated in the first place is an open and by no means settled question.

"Mutation Space"- A Potential Litmus Test

From the site:

http://www.ics.uci.edu/~aasuncio/idesign.htm

"Tuesday, April 04, 2006
Biological Interdependency and Mutation Space

Any software engineer can tell you that modularity is an essential characteristic of any program that must be actively developed, or even just maintained. Without modularity, any small change to one piece is liable to break a completely different piece in unpredictable ways. Adding a new feature to an unmodular system is difficult because it requires making many simultaneous changes to various pieces of a program that have no obvious relationship to each other or to the feature being added.

The same thing is true with Biology. In fact, it isn't controversial that the more complex an organism becomes, the less likely it is to evolve novel function, largely because of the intricate dependencies that must be maintained. What hasn't been attempted, so far as I know, is a quantification of approximately how much room an organism has in which to evolve – call this "mutation space" – as a function of its interdependecy complexity. In other words, how much functionality could be added/edited without requiring an unrealistic number of simultaneous compensatory changes elsewhere?

If it could be shown that any reasonably complex lower organism did not have room in its mutation space for the sort of evolution required to produce higher organisms (that is, any introduction of novel function would require an unrealistic amount of compensatory mutations to get off the ground), it would provide incredibly strong evidence for ID.

I'm not sure exactly how to quantify interdependency complexity and mutation space, but it seems like there ought to be a way to do it. Suggestions and/or reasons why this is a nutty idea that will never work are welcome."

[Bradford]: I'm not sure either. It looks like a complex undertaking. This is interesting in that at either extreme (life's origins or a highly complex organism) the generation of a novel biological system looks like a daunting prospect. At the point of origins the difficulty lies in generating a genetic structure with minimal function. No easy undertaking given the fact that maintenance functions such as the detection of genetic errors and their repair are found even in prokaryotic organisms. The inference that intolerable genomic corruption is inevitable in the absence of such functions is reasonable. In addition the encoded end products of DNA (proteins and RNA) are an integral part of the translation process and other encoded end products have vital roles in maintaining necessary cellular homeostasis. Yet faith in abiogenesis lives on.

The problem at the other extreme is of a different nature. As the author points out (my comments added in parenthesis): "Adding a new feature to an unmodular system (new function to a biological system) is difficult because it requires making many simultaneous changes (can require genetic changes affecting numerous interacting proteins) to various pieces of a program that have no obvious relationship to each other or to the feature being added" (or in the case of new biological systems indicate no intermediate pathways that are not the product of much imagination). The author's point is most clearly in evidence during prenatal development. Organisms develop in accordance with a tightly sequenced cascade of genetic instructions. Natural disruptions of them are evidenced in the form of birth defects.

Software engineers would be frustrated no end with the necessity of ignoring modularity in favor of always having to make a series of slight modifications of existing code to get from one objective to another. Engineers designing new vehicles want the freedom to eliminate and replace systems rather than having to modify only existing parts. There is a recognition that the degree to which change is limited by the necessity to alter existing parts also limits the viability and range of possible change. The interdependency and functional sequence relationship of parts determines the range of possible change. The capacity to generate biological change is not an exception to this principle.

The author's proposal to determine structural inhibitions to change by quantifying "interdependency complexity and mutation space" offers not only a means to evaluate the likelihood that novel biological functions evolve, it offers a measuring rod to determine limitations to change. ID has been criticized for lacking a mechanism for change and a predictive capacity. The mechanism in this case is the very same one cited by ID opponents. The prediction is that existing systems inhibit the type of changes required by an evolutionary paradigm. Evidence is found in hox genes. That entails a series of blog entries to come.

Genomic Similarities

[Bradford]: The following snippet comes from an exchange noted in the referenced article. I'll add to it.

http://www.newsobserver.com/102/story/432109.html

Van Dyke: "I would challenge Dr. Gray to give me any evidence of macro-evolution. I do not think, as a scientist, there is any evidence beyond micro-evolution to support [the idea] that we evolved from some other form of life."

Gray: "We are very closely related to the chimp."

Van Dyke: "Not really."

Gray: "Yes, we are. Ninety-six percent of our genome is virtually identical to the chimp. It is part of the species separation process."

Hambourger: "It just shows you how incredibly complex chimps are -- and we are."

[Bradford]: More precisely put it shows how differences in cellular differentiation can produce enormous differences in phenotype. The genome of your liver cells is 100% identical to the genome contained in the cells of your lungs.

Jesseph: "The intelligent design theory just doesn't cut it. Even with a lot of improvement, it would still be lousy science. It is not even up to the level of voodoo.

[Bradford]: The smashmouth approach to advocacy.

The main problem is it doesn't explain anything.

[Bradford]: It explains as much as the claim that result x was not the result of an intelligently directed cause. The point of concern should be the accuracy of competing claims.

To be told that fundamental elements of living things were designed by a designer about whom we know nothing other than he is intelligent and he designed is really to go nowhere. That's like explaining the inebriating properties of beer by the fact that it has a special drunk-making quality in it that is such that when you drink it you become inebriated."


[Bradford]: Hmmm. Then how does the claim that life arose as a result of unspecified natural causes, devoid of intelligent input, explain anything at all? A claim that DNA is the product of intelligent causality would free us of the futility of looking for a chemical cause for the sequential order of nucleotides necessary to create a functional, minimal genome. Scramble the nucleotides of a functional genome and you can create junk from order; dysfunction from what was functional. Yet you still have DNA. You still have the biochemical components of that nucleic acid. The functional nature of DNA owes itself to an encoding sequential order. This in turn is determined by the functional nature of the encoded gene end product within the context of the genome in question. Looking for a minimal genome arising from a fortuitous series of prebiotic chemical interactions is as revealing as Jesseph's beer analogy and a greater waste of time and resources.

Hambourger: "I think there is a serious danger that only you can know by looking into your own soul ... that secularists are motivated not by a genuine love of freedom and the Constitution but in many cases by a real dislike of religion.

"If those are your motives, I think it's important for you to realize you are in danger of two things: One is you are being extremely intolerant, and secondly, you are being a real hypocrite in trying to do so on the grounds of civil liberties."

[Bradford]: In other words the legal arena will not settle the issue. The truth is anti-IDers simply lack the scientific evidence needed to refute intelligent causality at the origin of life itself. Based on evidence the best they can do is argue that the question is an open one. When nucleic acids are the focus, they are at a disadvantage even trying to maintain this. Hambourger has identified the real motivation.

Natural Selection on Center Stage: Part Two

Here is another part of Princeton University President Shirley M. Tilghman's George Romanes Lecture at Oxford University on 12/1/05. The speech entitled 'Strange Bedfellows: Science, Politics and Religion' is referenced at the following URL:

http://www.princeton.edu/president/speeches/20051201/index.xml

Her comments are preceeded by the > symbol. Mine are not.

>"Today, however, under the banner of "intelligent design," Christian fundamentalists in the United States have launched a well-publicized assault on the theory of evolution, suggesting that the complexity and diversity of nature is not the product of random mutation and natural selection but rather of supernatural intent."

The useage of the term "Christian fundamentalists" is purposeful even if it it vague and misleading. Fundamentalist is a word used when one wishes to pejoritively paint an opponent. It generally equates to conservative Christian but has the added advantage of lumping them in the same thought category as those despised Middle Eastern fundamentalists.

If you come to subconsciously associate those who destroyed the World Trade Center with advocates of intelligent design as a result of repeated exposure to this type of lexicon then the purpose has been served. Never mind that there are Jewish and Muslim IDists or that there are Christian IDists who are not "fundamentalists." After all why let the facts get in the way of a useful prejudice.


>"Although exponents of intelligent design have been at pains to distance themselves from overtly religious interpretations of the universe, the intellectual roots of intelligent design can be traced to creationism, which holds that the natural world, including human beings in their present form, is the handiwork of a divine designer — namely, God. Biblical creationists contend that the world was created in accordance with the Book of Genesis — in six short days — while the followers of intelligent design eschew this literalism. They say that their goal is to detect empirically whether the "apparent design" in nature is genuine design, in other words, the product of an intelligent cause. They reject out of hand one of the central tenets of natural selection, namely, that biological change arises solely from selection upon random mutations over long periods of time. For those of you who are not conversant with the literature of intelligent design, the argument usually begins with Darwin himself, who said "If it could be demonstrated that any complex organ existed which could not possibly have been formed by numerous, successive, slight modifications, my theory would absolutely break down." From there, advocates such as Michael Behe, a professor of physical chemistry at Lehigh University, declare that "natural selection can only choose among systems that are already working, so the existence in nature of irreducibly complex biological systems poses a powerful challenge to Darwinian theory. We frequently observe such systems in cell organelles, in which the removal of one element would cause the whole system to cease functioning."

>"What is wrong with this view? To begin with, it reflects a fundamental misunderstanding of how evolution works."

This is a frequent criticism. If you believe natural selection does not adaquately explain the evolution of biological systems composed of dozens of interacting proteins then you must not understand how evolution works. Behe well understands the concept of natural selection. Others who share his doubts also understand the mechanisms on which natural selection is said to act. Behe's description of irreducibly complex biological systems as a challenge to Darwinian theory is apt in that biology is an empirical discipline and we do not observe the evolution of such systems. Instead we are treated to logical arguments like the one that follows.

>"Nature is the ultimate tinkerer, constantly co-opting one molecule or process for another purpose. This is spurred on by frequent duplications in the genome, which occur at random. Mutations can accumulate in the extra copy without disrupting the pre-existing function, and those that are beneficial have the potential to become fixed in the population. In other instances, entirely new functions evolve for existing proteins."

This argument says to the reader "reverse the sequence of events and see how irreducibly complex systems could have evolved." Let's do exactly that and follow the trail to a very basic biological system that is a prerequisite to the biological systems alluded to by both Behe and the author. Lactate dehydrogenase and the numerous proteins mentioned by Behe in 'Darwin's Black Box' owe their existence to biological systems that enable protein synthesis. Encoding genes are first transcribed and then translated in a process that yields encoded proteins. Numerous proteins are part of both the transcription and translation mechanisms. These proteins are themselves synthesized by the mechanisms of which they are component parts. How did natural selection produce a protein synthesis function? What would have been the selective value of any protein at a point in time when no protein synthesis mechanism existed? The translation function fits Behe's definition of an irreducibly complex biological system. Describing its existence as "a powerful challenge to Darwinian theory" is right on target. Citing mutations of gene duplications is not useful unless a means of expressing mutated genes exists.

>"My favorite example is lactate dehydrogenase, which functions as a metabolic enzyme in the liver and kidney in one context, and as one of the proteins that makes up the transparent lens of the eye in another. In the first cellular setting, the protein has a catalytic function; in the second, a structural one."

A realistic approach entails documenting the appearance of proteins forming novel functions. Irreducibly complex systems are composed of interacting proteins. Demonstrating the evolution of such systems involves detailing the sequential pathways to their constituent proteins.

Natural Selection on Center Stage: Part One

On 12\1\05 Shirley M. Tilghman, President of Princeton University, delivered the George Romanes Lecture at Oxford University. The speech entitled 'Strange Bedfellows: Science, Politics and Religion' is referenced at the following URL:

http://www.princeton.edu/president/speeches/20051201/index.xml

A part of the speech concerning natural selection and intelligent design is noted here and comments are directed at it. From the speech:

>"If cosmologists are deciphering the origins of the universe and our solar system in unprecedented ways, biologists are making enormous strides, thanks to the technology that was developed during the Human Genome Project, toward unlocking the origins of life on Earth. Yet here, too, science and politics have found themselves at loggerheads. It is impossible to ignore the increasing assertiveness of elements within American society who have challenged the validity of Darwin's theory of natural selection and have lobbied for an alternative explanation, which they term "intelligent design," to be taught in public schools alongside the principles of evolution. This is deeply disturbing, for the theory of natural selection is one of the two pillars, along with Mendel's laws of inheritance, on which all of modern biology is built."


Natural selection is indeed a theoretical pillar of evolution. Initially invoked by Darwin as a logical argument, it remains primarily a logical rather than an empirical device. Tilghman's use of the term natural selection infers that intelligent causality and natural selection are mutually exclusive concepts. But are they?

Examples of natural selection have focused largely on adaptations found in unicellular organisms and insects; organisms with high rates of reproduction. Of course in all organisms lethal genetic changes are eliminated from the gene pool as well. What we do not observe is the generation of new biological systems consisting of a large complex of interacting proteins. If natural selection accounts for the existence of such systems then what is the evidence? Citing the selective value of a protein or complex of proteins is akin to stating there is biological utility in their function. Parallel functions can be identified in enzymes found throughout the living world. Identical substrates can be catalyzed by enzymes found in very different organisms. Given that the primary structure of such enzymes is very similar a case for common descent is made. Whether attributed to common descent or common principles of design an identical substrate can dictate the constituent residues of an active site. Explaining that nearly identical enzymes of different species associate with metal ion cofactors with invarient atomic structures like zinc or iron tells us of an affinity between them and shared amino acids. That affinity is a cause of the enzyme similarity. A cause linked to natural history entails a secondary inference which is intrinsically less reliable as a causal factor. More from Shirley M. Tilghman:


>"It is virtually impossible to conduct biological research and not be struck by the power of Darwin's theory of natural selection to shed light on the problem at hand. Time and again in the course of my career, I have encountered a mysterious finding that was explained by viewing it through the lens of evolutionary biology. The power of the theory of natural selection to illuminate natural phenomena, as well as its remarkable resilience to experimental challenge over almost 150 years, has led to its overwhelming acceptance by the scientific community."


Too bad we were not treated to an example of an explained mysterious finding. There are many unmysterious biochemical reactions that do not lend themselves to natural selection explanations devoid of an unacceptable level of speculation. Pyruvate is converted to acetyl CoA by what is known as the pyruvate dehydrogenase complex consisting of three distinct enzymes each catalyzing a part of an overall reaction. Regulatory enzymes are also involved in the process. There would have been a point in time when none of the enzymes existed as well as none of their encoding genes. There is no question about the biological utility of the enzymes to the conversion. It is equally clear that the enzymes operate in concert to effect the conversion. What does natural selection tell us about the evolution of this complex? No doubt imaginative minds can conjure up an evolutionary pathway but like other putative precursor pathways it would raise more questions than it answers. As we trace our steps backward it becomes increasingly apparent that the theoretical underpinnings of selection concepts becomes more vague and predictions less reliable as natural selection faces the task of explaining the genetic ediface on which the mechanism depends. Natural selection becomes less reliable even as a logical indicator when the selection criteria needed to generate a minimal functional genome is not even known.

The author links the utility of natural selection to research and in doing so comes squarely in conflict with the views of Professor Philip Skell. His comment and the referenced URL for the article follow:

http://www.evolutionnews.org/2006/04/post_11.html

"Last year, Dr. Philip Skell, Emeritus Evan Pugh Professor at Pennsylvania State University and a member of the U. S. National Academy of Sciences, wrote in The Scientist that he"

"examined the outstanding biodiscoveries of the past century: the discovery of the double helix; the characterization of the ribosome; the mapping of genomes; research on medications and drug reactions; improvements in food production and sanitation; the development of new surgeries; and others. I even queried biologists working in areas where one would expect the Darwinian paradigm to have most benefited research, such as the emergence of resistance to antibiotics and pesticides. Here, as elsewhere, I found that Darwin's theory had provided no discernible guidance, but was brought in, after the breakthroughs, as an interesting narrative gloss."

That's my take as well. Natural selection is brought in to explain results rather than as a guide toward them.

Detecting Intelligence in Life's Origins

Pathways to life are envisioned as processes in which random chemical reactions assume a direction toward a living cell. The direction is provided by the natural selection concept. Prior to a point in time when no genome existed, favorable genetic changes would not be invoked by natural selection. So what would be selected and why? The starting point for some involves theorized self-replicating molecules; molecules which participate in the generation of more of the same molecules as long as a supply of reactants is available. For others a series of unknown chemical interactions led to that first cell with replicating qualities from which life evolved. Neither scenario provides a directional compass.

Self-replicating molecule enthusiasts believe such molecules provide both replication qualities and a selection basis pointing the compass toward a first cell. "Mutations" in the process would lead to other self-replicating molecules and eventually a replicating cell. If this sounds like vague, wishful thinking then your appreciation of cellular biology has gotten in the way of mistaking ideological hype for a scientific hypothesis.

While Darwinists have prevailed against Paley and other proponents of design by referencing natural selection as the driving force behind evolution they have avoided, like a skilled matador, having to designate how and on what natural selection would act in driving unspecified reactions toward that initial putative cell. The theoretical deficiency undercuts a natural alternative to intelligent causality at the point of origins.

The argument posed and explored at this site is that intelligence better explains the origin and diversity of life than the contention that life arose and subsequently evolved in the absence of intelligent guidance. The working definition of intelligence is cited from an article appearing in the 12/13/94 edition of the Wall Street Journal referencing a group of 52 psychologists and this:

"Intelligence exists as a very general mental capability involving ability to reason, plan, solve problems, think abstractly, comprehend complex ideas, learn quickly and learn from experience."

Evidence of reason, planning, problem solving and abstract thinking must be detectable in biological systems. The evidence will be cited and argued without heed to the objection that a supernatural cause decouples the effort from empirical consideration. The objection is religious in nature; entailing a limited set of theological assumptions and presuming a consensus about the interface between the natural and the supernatural. It is also intrinsically anti-intellectual requiring belief in predetermined conclusions. Evidence and sound reason are the standard by which to gauge standard theories as well as alternatives to them. The standard will be probed and tested in the posts that follow.