You just gotta love the guy. He treated the culture war with as much respect and dignity as it deserves, which to John meant absolute scathing irreverence and mockery.

Goodbye, John.

"Thank you for allowing me to instigate all of you into so freely exposing your monumental ignorance, your bigotry and your "prescribed," "born that way," congenital "groupthink" mentalities for all to see and savor. The pleasure has been mine, all mine.

It is hard to believe isn't it?

I love it so!"

-JAD

[Obituary.]

•This ancestral mechanism diverged into the six modern mechanisms.

•The divergences in mechanisms relate to key branching events in evolutionary development.

•The ancestral mechanism was robust, redundant, multi-layered, and poised to exploit future environmental changes such as increased oxygen levels.

Viewed under the mindset of abiogenesis, biologists see the picture of early life as klunky, unrefined and highly unstable. As researcher Eric Smith says, "It seems likely that the earliest cells were rickety assemblies whose parts were constantly malfunctioning and breaking down".

But if we instead view this under the mindset of design, we actually see some very ingenious design principles at work. Mainly, this is an amazingly adaptive system. Check it out:

•Redundancy – one system breaks down, another is there to do the job.
•Multi-layered – several different mechanisms in play simultaneously.
•Support for future contingencies – ie: designed for anaerobic environment but ready to exploit an aerobic environment.

This was a robust system that was prepared to adapt to many environmental variables. Not only would this system facilitate future evolutionary divergence, and novel processes like photosynthesis, but it also seems geared to support protein based biology.

It was a major stroke of luck for dirt to accomplish this all by itself.

Engineers, however, will recognize this as just good, sensible, intelligent design.

Scientists are no different from most people. Dangle big wads of cash or prestige in front of them and they'll do just about anything to get it. Here's some key quotes:

During a decade as head of global cancer research at Amgen, C. Glenn Begley identified 53 "landmark" publications — papers in top journals, from reputable labs — for his team to reproduce. Begley sought to double-check the findings before trying to build on them for drug development.

Result: 47 of the 53 could not be replicated.

Note this is not a random sampling. It represents what the head of Amgen research thought was "the best of the best" in cancer research.

Scientists at Bayer did not have much more success. In a 2011 paper titled, "Believe it or not," they analyzed in-house projects that built on "exciting published data" from basic science studies. "Often, key data could not be reproduced,"…Of 47 cancer projects at Bayer during 2011, less than one-quarter could reproduce previously reported findings, despite the efforts of three or four scientists working full time for up to a year.

You know, when supposed cold-fusion experiments turn out to not be replicable it usually means public disgrace. Why is there no disgrace in cancer research, especially when the public is pouring money into the enterprise?

Bayer and Amgen found that the prestige of a journal was no guarantee a paper would be solid.

Apparently upwards of 75% of the time in some fields. So much for peer review.

"We went through the paper line by line, figure by figure," said Begley. "I explained that we re-did their experiment 50 times and never got their result. He said they'd done it six times and got this result once, but put it in the paper because it made the best story. It's very disillusioning."

Mmmm. Smell the hubris.

On Tuesday, a committee of the National Academy of Sciences heard testimony that the number of scientific papers that had to be retracted increased more than tenfold over the last decade; the number of journal articles published rose only 44 percent. Ferric Fang of the University of Washington, speaking to the panel, said he blamed a hypercompetitive academic environment that fosters poor science and even fraud, as too many researchers compete for diminishing funding.

This needs no commentary. I just wanted to say "Ferric Fang" is one of the coolest names ever. Iron Tooth! Awesome.

"If you can write it up and get it published you're not even thinking of reproducibility," said Ken Kaitin, director of the Tufts Center for the Study of Drug Development. "You make an observation and move on. There is no incentive to find out it was wrong."

Science without testing and falsification is not science. It's just observation and hypothesis – also known as speculation. Karl Popper went as far as to call it pseudoscience. Now we have an entire scientific enterprise that is taking your tax money and your donations not for research, but to speculate.

Some public disgrace should be in order.

We often hear talk of scientists claiming that evolution is a purposeless process. Some claim that purpose is an illusion because of evolution by natural selection. For example, Professor Larry Moran, a Professor in the Department of Biochemistry at the University of Toronto has this to say:

“One of the most astonishing discoveries of modern science is that the universe does not exhibit any signs of "purpose" or "goals." This single conclusion is probably more responsible for the profound conflict between science and religion than any other. The attractiveness of religion was that it seemed to answer the "why" questions that science, presumably, could not answer. Now, modern science tells us that the question was meaningless.”

He goes on to cite two other scientists, Douglas Futuyma and Richard Dawkins, who share the same views regarding purpose and evolution. Professor Moran also argues that this view comes naturally to many evolutionary biologists. This may very well be true for the majority of evolutionary biologists.

The question of whether there is purpose or not is of course not something that can be solved with empirical science. There is no experiment to test whether there is or isn’t purpose. Scientists do not qualitatively or quantitatively measure whether there is purpose. They don’t look through a microscope or use some other instrument and conclude that there is no evidence of purpose within a 99% interval of certainty. In other words, the question regarding whether there is or isn’t purpose is irrelevant to the empirical and real sciences. Professor Moran is right on this, the question of purpose is meaningless to empirical science. Empirical science does not deal with the question of purpose.

The question of purpose is for the logical and rational sciences. You guessed it, it is ultimately a metaphysical issue. Aristotle was one of the first to provide a full treatment of the concept of purpose. Later, scholars such as Aquinas built upon his ideas. For Aristotle, the purpose of something is identified with its natural ends or final causes. Teleology is the view that natural ends are natural phenomena and intrinsic to natural substances. Aristotelian teleology can be distilled to its simplest form as “every agent acts towards an end”.

I will use three simple examples to explain what this means. Firstly, an example of two electrons being repelled. Secondly, the role helicase proteins play in replication. Lastly, the example of gravity.

For electrons, simply put, the natural ends of electrons are;

1) The generation of an electric field.

2) The generation of an electrostatic potential.

3) The generation of a magnetic field.

4) The generation of a vector potential.

What happens with two interacting electrons is that each electron generates an electric field (among other natural ends). These fields interact and generate a force. This force results in the movement of the electrons away from each other. The electrons, interacting electric fields and forces all have natural ends and these include the generation of electric field, generation of force and generation of movement respectively.

Helicases are known to be ring-shaped (typically hexamers) motor proteins. DNA replication occurs at about 1000 base pairs per second. In the cell, DNA forms a double helix. However, during DNA replication in a cell helicases unwind DNA. They unwind DNA at about the same speed that DNA replication occurs. Helicase is the blue, round protein unwinding the DNA in red in this video (at around 2:00-2:30 mins). Simply put, the natural end of helicase is to unwind DNA.

Gravity is a force that causes objects of mass to attract each other with a force proportional to their mass. Therefore, it simply follows that the natural end of gravity is to attract objects of mass with a force proportional to their mass. We may not know much about the mechanisms of gravity. There are various theories in loop quantum theory or M-theory etc. This however, does not take away what we know about gravity's natural ends.

Aristotelian teleology is a simple concept to grasp. Importantly, it should not be confused with Paley's or the IDers' "complexity" arguments for design. Richard Dawkins is an example of someone that mistakenly confuses Aristotelian teleology for Paley's views on design. In his book "River out of Eden", he writes:

"Notoriously, of course, the apparent purposefulness of living bodies has dominated the classic Argument from Design, invoked by theologians from Aquinas to William Paley to modern "scientific" creationists."

In his book, "The God Delusion" Dawkins also deals with Aquinas' teleological argument. Dawkins does not appear to be aware of the simple fact that the fifth way has NOTHING to do with Paley's watchmaker analogy or ID. Dawkins completely misses this and tears down a straw man. So to be sure, Aristotelian teleology and design arguments from complexity are very different and one should NOT be confused with thinking they are the same.

As it turns out, even Darwin was a teleologist. Darwin had good things to say about Aristotle. From Allan Gotthelf's article "Darwin on Aristotle": Darwin in a letter to William Ogle:

"Linnaeus and Cuvier have been my two gods, though in very different ways, but they were mere schoolboys to old Aristotle."

The reason why Darwin was a teleologist is associated with his view of natural selection. Darwin's idea of natural selection preserves elements of Aristotle's teleology. Professor Andre Ariew points out (in his article "Platonic and Aristotelian Roots of Teleological Arguments in Cosmology and Biology") that:

“How is natural selection a teleological "force"? I see remnants of two sorts of teleology operating in Darwin. The key to seeing both is within Darwin’s concept of natural selection which can be summed up as follows: as a result of individuals possessing different heritable abilities striving to survive and reproduce in local environments, comes an explanation for changes in trait composition of populations through time. Traits become prevalent in populations because they are useful to organisms in their struggle to survive. Aristotle's functional teleology is preserved through the idea that an item's existence can be explained in terms of its usefulness (Lennox 1993). What makes a trait useful is that it provides certain individuals an advantage over others in their own struggle to survive and reproduce. Secondly, the concept of individual striving to survive and reproduce plays the fundamental role in Darwin's explanation for the origins of organic diversity. The same concept reminds us of Aristotle's formal teleology – the striving for self-preservation.”

The natural ends of natural selection are just to "maximize reproductive success in particular environmental niches".  Alternatively, it "maintains” the prevalence of beneficial mutations. On the other hand, it "limits" or "favours" some variations over other variations. Natural selection may "steer" biological change toward the local maxima in the "fitness landscape". So it turns out even natural selection has a natural end if we accept that it is a real cause and force of evolution and not merely a descriptive term.

Professor John O. Reiss also notes that the fitness landscape metaphor has teleological implications. Implicit in the fitness landscape metaphor is the view that natural selection acts "as a force driving the population toward this improved future state". If evolution is anything close to the metaphor then the process is fundamentally teleological. The natural end of evolution, if the fitness landscape was not metaphorical, would then be improved future states.

Where then is the purposelessness of evolution? Perhaps it is associated with random variation. As it turns out, the random part in random variation is not really random when it comes to mutations. Professor Dan Graur writes in his article “Single-base Mutation” in Encyclopedia of Life Sciences that mutations do not occur randomly throughout the genome and the direction of mutation is not random. The only way variation is seen as random is that it is random in respect to the effect variation has on fitness.

The major problem with this is that the precise meaning of fitness has not been settled. There is still a major debate about what exactly fitness is supposed to mean (see this post for more on this issue).

John O. Reiss also makes the following interesting remark:

“The rigor of this approach, however, is lessened because there is as yet no universally agreed upon measure of fitness; fitness is either defined metaphorically, or defined only relative to the particular model or system used. It is fair to say that due to this lack, there is still no real agreement on what exactly the process of natural selection is. This is clearly a problem.”

Without a proper definition of fitness, we can’t really say what natural selection is. Also, without a proper definition of fitness we can’t really make any sense of how variation can be random relative to fitness in the first place. Still, some evolutionary biologists would like to see evolution as "random, purposeless variation acted on by blind, purposeless natural selection". Stephen L. Talbott in his article Evolution and the Illusion of Randomness makes this point much more forcefully.

Yet, on a macro level, we observe the natural ends of organisms. Eating, breathing, mating etc. are all natural ends of living organisms. On a molecular level, the wonderful natural ends of molecular machines and even simple chemical reactions are all there. Moving to ever-smaller things we also see elementary particles acting for an end e.g. generation of fields, forces electrostatic potentials etc.

However, as Stephen Talbott point out, we are to believe that all these natural ends and evolution are apparently because of more basic processes that are essentially random, purposeless or without any natural ends. The question is where are these purposeless and random processes? Which gap do they fit in? What are these assertions based on? They certainly are not based on any empirical science and it looks like a "purposelessness of the gaps" kind of argument.

Among his various "cures" for the planet's fever are:

1) A "meat patch" that makes you puke when you eat meat.
2) Hormones that stunt your children's growth.
3) Drugs that make you want to write checks.
4) Genetically engineering humans with "cat eyes" so we don't need light bulbs.

Of course, Matthew assures us that no one will be forced to do any of these things. The government will simply set limits to how much carbon your family can produce or set drastic limits on consumption. Then you get all the freedom you need to decide whether you want to have 2 really small children, or one medium sized child, or perhaps one large child who will be required to wear a "meat patch".

Progressivism! Enhancing your freedom – by limiting your freedom!

No, it's not a joke.

"Isn't it about time someone created a junk yard dog style outfit like Eugenie Scott's racket, except on the other side, to be a continuous hammer on the heads of the Darwinista liars, deceivers, and disinformationists with respect to public schools?

I say yes."

I respond: What possible good could come from that?

Kornbelt, you might just as well start a watchdog organization that debunks and exposes the failings of the Taliban. And for all your hard work, the next time they behead some woman in a soccer stadium they will blame your organization for corrupting her.

It's not like you're dealing with deliberative, rational, critical thinking, honest truth seekers. The folks at the NCSE imagine themselves to be some self-appointed warrior class, sworn to the cause of protecting society. They are entrenched, indoctrinated, dedicated, and they really, really like what they do. You aren't going to change that.

Kornbelt, the only thing to do is teach your children to be honest men and women of good character. Teach them to value truth and humility, and to eschew duplicity and bigotry. Teach them the 10 signs of intellectual honesty. The Eugenies, the Gleicks, the Matzkes, the Rosenhouses, the Hesses will become such a stark contrast that no honest young person would ever in a million years take them seriously. These papier mache warriors really are nothing to worry about. And they'll be gone anyway in 30 or 40 years or so.

And it helps to laugh heartily at all the culture warriors while we're waiting for them to leave the planet. They are, after all, little more than overgrown children playing dwarves and trolls in the woods with styrofoam swords. Utterly harmless. Utterly silly. Instead of fashioning our own styrofoam swords and cardboard shields, I humbly suggest instead we make some popcorn, set out some lawn chairs and watch the show. They are not dangerous.

As Jesus said of another famous culture warrior, they would have no power were it not given to them from above.

This is an interesting statement. You often hear or read about this in conversations and debates surrounding the existence of God. A person may ask another person “why are you an atheist” and the atheist may reply, “purely because there is no evidence for God”.

As always, definitions play a crucial role in any debate and conversation. I cannot claim that there is no evidence for the existence of Bodwilstin if I do not have a definition for it. If someone asks me why I am an aBodwilstinist, I cannot tell that person “purely because there is no evidence for Bodwilstinist”. I do not even have a clear definition of what it is that there is no evidence of. So the “there is no evidence” line is irrational if an atheist does not have a definition of God. The most rational stance towards something for which there is no definition is agnosticism or ignosticism.

The standard classical theist view or definition of God is that if God exists then nothing can come into being or continue to happen without God creating it and sustaining it in existence.  If classical theism is true it just logically follows that every contingent being that has ever existed and will ever exist is evidence for the existence of God. It does not matter if the universe has existed for infinity, if abiogenesis is true or false, if there is a multiverse or if humans had a common ancestor with other apes or not or all of the above etc. Of course, defining something does not mean it exists or that it is logically coherent. It may be that theism is false and have better other explanations for why things begin to exist and continue to exist.

For the classical theist, the existence of God can be known via reason and logic. To give an example, Aquinas’ second argument (First Cause) is a standard logical demonstration. It follows the same reasoning as mathematical proofs. The following principles are important:
1) The Principle of Causality
2) The distinction between essence and the act of existing.
3) The distinction between per accidens causes and per se causes.

1) The Principle of Causality
The traditional view is that:
1) "Whatever happens has a cause; Whatever begins to be has a cause; Whatever is contingent has a cause; Nothing occurs without a cause."2) The axiom Ex nihilo nihil fit (from nothing, nothing comes) is a negative statement of the same principle.
3) Another way of saying it is “something can only be reduced from potentiality to actuality by something in a state of actuality” (Aquinas, a Beginner's guide, p65).

From an Aristotelian-Scholastic point of view, the empirical data from quantum mechanics pose no problem for the principle of causality. In fact, quantum physics and the Aristotelian concepts of prime matter and pure potentiality actually fit in quite nicely with the indeterminate nature of quantum physics. As explained here. In addition, some might argue that science has demonstrated that "from nothing, nothing comes" is false. Such assertions are usually based on a faulty or inadequate definition of "nothingness".

2) The distinction between essence and the act of existing.
Another principle that is important in Aquinas' second way is the distinction between something's essence and its act of existing.

Take the example of water. When you think about water you may ask "what is water"? To answer such a question is to provide the essence or nature of water. From an Aristotelian point of view, when one fully understands what water is one knows its full essence or nature. One can of course come to understand some part of the essence of water without it ever actually existing or experiencing it the moment you understand it. You can now think about the concept of water and fully understand it. However, from a Scholastic point of view, when you see a drop of water, the water is actually existing. That is, the essence of water is combined with its act of existing.

Also, material substances begin to exist. You and me for example did not exist 200 years ago. We began to exist at some instant. The same goes for a water molecule when it begins to exist in a reaction between hydrogen and oxygen. So let's use the example of water.

Before the water begins to exist you can still intellectually abstract what it is, you grasp its essence. However, the moment it begins to exist its essence and act of existence are conjoined to form a complete actual material substance. From a Scholastic point of view all actually existing material things right here right, right now are complete substances whose essence or nature are conjoined with their act of existing.

3) The distinction between per accidens causes and per se causes.
A third important principle is the distinction between accidentally ordered causes and essentially ordered causes. Accidentally ordered causes (per accidens causes) are prior in time. Essentially ordered causes (per se causes) are prior in nature.

Let's use the water example again. Hydrogen and oxygen in this case are the per accidens causes of water. They are accidentally ordered causes. Hydrogen and oxygen occurred prior to the water that came into existence as a result of these accidental causes.

Now the water in the reaction began to exist. The moment water started to be an actually existing material substance, its essence is conjoined with its act of existing. Also, whenever water is actually existing its essence is continually conjoined with its act of existing. The next question is “what causes its essence to be conjoined to its act of existing”? It can't be something that exists before it came into being. In other words, it cannot be an accidentally ordered cause. It has to be something that is also actually existing the very same moment the water exists. It thus follows that it is something that is an essentially ordered cause but is prior in nature (not time) to the water.

Aquinas’ argument using the water example can thus be summarized as follows:
1) Whenever water begins to actually exist, its essence is conjoined with its act of existing.
2) Something causes the essence of water to be conjoined to its act of existing.
3) Such a cause cannot be water itself and the cause has to be prior in nature and not prior in time (as argued above).
4) The cause may be something contingent.
5) Everything that is contingent has an essence that is distinct from its act of existing (as argued above).
6) If the cause is something that is contingent then it too needs a cause to conjoin its essence with it act of existing.
7) However, essentially ordered causes cannot go on to infinity, as there would then be no explanation for why something begins to exist.
8 ) The First Cause in an essentially ordered series of causes will have to be something whose essence is not distinct from its act of existing. Something whose essence is its act of existing. For the classical theist this is God.

Aquinas' second way gets you to something whose essence is its act of existing. Now this kind of argument is not meant to convince everyone. I think it is unreasonable to think this. In fact, I think it is unreasonable to even think that standard mathematical proofs are meant to convince everyone. Some people may be ultra-skeptics and claim nothing can be known with absolute certainty or any kind of certainty at all. Some might argue that consciousness and your intellect are illusions. Still others just don’t care.

The point is, for the classical theist, God can be known via reason and logic. Classical theism is affirmed by Christian, Jewish, Muslim and Pagans thinkers such as Aquinas, Maimonides, Avicenna and Plotinus respectively. Aquinas’ five ways can in principle demonstrate the existence of something that just is necessary being itself (3rd way), whose essence is its existence 2nd way), that is intelligence analogously speaking (5th way), that just is good (4th way) and is purely actual (1st way). That is what classical theists call God.

It is accepted based on the coherence of the definition of God not because there is no evidence. If a person is or was a classical theist then he accepts it or rejects it not because of the evidence. One accepts or rejects classical theism based on reason and logic.

Rational acceptance or scepticism of theism
Now there are of course the standard philosophical problems with classical theism. Alisdair McinTyre summarizes the three main problems in his book "God, Philosophy, Universities: A Selective History of the Catholic Philosophical Tradition".

The first problem is associated with the view that finite contingent beings have powers of their own. For example, water has the power to dissolve salt. Humans have the power to have rational thoughts. Magnets have the power to attract or repel each other. However, if God exists then God is the cause of every change, every contingent power. This appears to be a problem for the view that humans are accountable for their actions and have their own powers (and anything else that has its own powers) to do things. So the classical theist has the problem of reconciling his view of his independent powers (and that of other things) and that of God’s unlimited power.

The second problem is associated with the various evils (natural, social and moral) associated with finite beings. If the following is correct:
1) God is unlimited in power and goodness and wills the good of every finite being.
2) Evil occurs and this entails that God is responsible for evil.
then the classical theist is faced with believing a logical contradiction.

The third problem is associated with how we can even talk meaningfully about God. Since we are contingent finite beings, all our descriptions of God e.g. God’s power, goodness, knowledge etc. are limited. We may use comparative and superlative linguistic inventions by describing power and goodness and knowledge as either more or less but we are never able to fully understand the full essence of what it actually means to have unlimited power, goodness and knowledge since we are finite, contingent beings.

The rational way, I would argue, is to engage in solving these problems. Those are examples of how one can rationally and logically accept or reject or be sceptical ofclassical theism. If such problems can be solved, again via reason and logic, then one can rationally accept classical theism. If not, one can reject it or be sceptical or be agnostic.

Now the person that claims to be an atheist “purely because there is no evidence for God” can make this claim as a result of:
1) Some strange definition or view of God which no classical theist really accepts. It would essentially be a straw man objection to view of God that theists probably don't have.
2) Having no definition of God so he has no way of even having any evidence at all anyway. But this is of course irrational. You can't rationally and logically claim there is no evidence for something which you don't even have a definition for.
3) Accepting the standard view of God and still claim there is no evidence. But this is irrational. It amounts to saying something like "I accept that the definition of the X, whereby if X exists one would expect to see boiling water. I see boiling water but I don't believe in X because there is no evidence for X". Or to put it differently, "I accept the standard view of God whereby if God exists then nothing can come into being or continue to happen without God creating it and sustaining it in existence. I exist, but I don't believe in God because there is no evidence for God".

None of the above reasons for the "there is no evidence" objection really make sense from a theistic point of view. The objections appears irrational or they just miss the point completely. The next obvious question is, if you claim there is no evidence for the existence of God, what exactly are you talking about? In what way do you think it even makes sense to make such a claim? Why do you think this is not a face-palm worthy claim?

Apparently, the fortunes of Dawkins' ancestors were built on the backs of slaves. You see there is a reason for this – evolutionary psychology. Our selfish genes drive us to behave in ways that propagate them.

In the case of slavery, more slaves result in greater wealth and we all know how greater wealth results in increased propagation for selfish genes. The trick in those days was to keep the slaves once you have them. The best way to do this was to try to keep them uneducated.

Richard Dawkins' selfish genes are still driving him to behave in ways to propagate them.  Unfortunately for him slavery has been abolished, and rightly so. Therefore, the next best thing to have is zombies. The mechanics are the same. More zombies that buy your books and T-shirts and bingo, propagation of selfish genes AND memes. The trick in keeping zombies is also to keep them uneducated and in this case, un-educable.

Dawkins is quite good at zombie herding. First he writes a few sciency books to give him some street cred as a scientist. Then he writes The God Delusion. By the time some people begin to realize the logical fallacies and bad scholarship in the book it is too late. The gnu zombies are hooked on bad philosophy and metaphysics masqueraded as science and scholarship. If you point out that Dawkins can't even get Aquinas' cosmological arguments right,  that he can't even distinguish between the teleological argument and Paley's watchmaker argument, that Darwin was a teleologist or that Dawkins' central argument is hopelessly flawed, all you get is the Myers Shuffle and cowardice to engage their critics. Gnu zombies are uneducated when it comes to philosophy, logic and metaphysics. And unlike slaves who are educable, gnu zombies appear to be immune to any form education that is contra their indoctrination.

You cannot really blame Dawkins for all this. Blame his zombie herding on his selfish genes he inherited from his slave-herding ancestors. Natural selection did result in the propagation of these selfish genes. And after all, no action no matter how stupid "is in principle to be blamed on antecedent conditions acting through the accused's physiology, heredity and environment".

Open Thread, Have Fun.

As always, the work of the Lenski lab is solid and interesting, but is spun like a top to make it appear to support Darwinian evolution more than it does. As the authors acknowledge, this is certainly not the first time a lab has evolved a virus to grow on a different strain of host. In a recent review (Behe 2010) ( http://tinyurl.com/25c422s ) there is a section entitled “Evolution Experiments with Viruses: Adapting to a New Host” discussing just that topic. In general, viruses have been shown to be able to adapt to bind to related host cells which have similar surface features. In almost all cases the virus uses the same binding protein, and the same (mutated) binding site to attach to the new host cell. This seems to also be the case with Lenski’s new work. As stated above, the first several mutations apparently strengthen the ability of the J protein to bind to the original site, LamB, while the fourth mutation allows it to bind to OmpF. As the authors state, however, the mutated viral J protein can still bind to the original protein, LamB, which strongly suggests the same binding site (that is, the same location on the J protein) is being used. It turns out that both LamB and OmpF have similar three-dimensional structures, so that strengthening the binding to one fortuitously led to binding to the other. In my review (Behe 2010) I discussed why this should be considered a “modification of function” event rather than a gain-of-function one. The bottom line is that the results are interesting and well done, but not particularly novel, nor particularly significant.

To me, the much more significant results of the new paper, although briefly mentioned, were not stressed as they deserved to be. The virus was not the only microbe evolving in the lab. The E. coli also underwent several mutations. Unlike for lambda, these were not modification-of-function mutations — they were complete loss-of-function mutations. The mechanism the bacterium used to turn off LamB in 99% of cells to resist initial lambda infection was to mutate to destroy its own gene locus called malT, which is normally useful to the cell. After acquiring the fourth mutation the virus could potentially invade and kill all cells. However, E. coli itself then mutated to prevent this, too. It mutated by destroying some genes involved in importing the sugar mannose into the bacterium. It turns out that this “mannose permease” is used by the virus to enter the interior of the cell. In its absence, infection cannot proceed.

So at the end of the day there was left the mutated bacteriophage lambda, still incompetent to invade most E. coli cells, plus mutated E. coli, now with broken genes which remove its ability to metabolize maltose and mannose. It seems Darwinian evolution took a little step sideways and two big steps backwards.

Literature Cited

Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

Meyer, J. R., D. T. Dobias, J. S. Weitz, J. E. Barrick, R. T. Quick et al. 2012 Repeatability and contingency in the evolution of a key innovation in phage lambda. Science 335: 428-432.

It seems to me that Richard Lenski, who knows how to get the most publicity out of exceedingly modest laboratory results, has taught his student well. In fact, the results can be regarded as the loss of two pre-existing abilities: 1) the loss of the ability to separate from the mother cell during cell division; and 2) the loss of control of apoptosis. The authors did not analyze the genetic changes that occurred in the cells, but I strongly suspect that if and when they do, they’ll discover that functioning genes or regulatory regions were broken or degraded. This would be just one more example of evolution by loss of pre-existing systems, at which we already knew that Darwinian processes excel. The apparently insurmountable problem for Darwinism is to build new systems.

Literature Cited

Ratcliff, W. C., R. F. Denison, M. Borrello, and M. Travisano, 2012 Experimental evolution of multicellularity. Proc. Natl. Acad. Sci. USA doi/10.1073/pnas.1115323109

I have written appreciatively about both Lenski and Thornton before, whose work indicates clear limits to Darwinian evolution (although they themselves operate within a Darwinian framework). Thornton’s latest work is beginning to show a convergence with Lenski’s that greatly boosts our confidence that they both are on the right track. In a recent review (Behe, 2010) I pointed out that all characterized advantageous mutations that Richard Lenski has observed in his twenty-year experiment have turned out to be degradative ones — ones in which a gene or genetic control structure was either destroyed or rendered less effective. (Random mutation is superb at degrading genetic material, which sometimes is helpful to an organism.) In his latest work Thornton, too, shows evolution of a system by degradation, although he speculates that the changes were neutral rather than advantageous.

In Finnegan et al (2012), “Evolution of increased complexity in a molecular machine”, Thornton and colleagues study a ring of six proteins in a molecular machine (that also has many other parts) called a V-ATPase, which can pump protons (acid) across a membrane. The machine exists in all eukaryotes. In most eukaryotic species, however, the hexameric ring consists of five copies of one protein (let’s call it protein 1) and one copy of another, related protein (call it protein 2). In fungi, however, the ring consists of four copies of protein 1, one copy of protein 2, and one copy of protein 3. Protein 3 is very similar in sequence to protein 1, so Finnegan et al (2012) propose that proteins 1 & 3 are related by duplication of an ancestral gene and subsequent modification of the two, originally-identical duplicated genes.

How did protein 3 insinuate itself into the ring? The original protein 1, present in five copies in most organisms, already had the ability to bind to itself, plus an ability to bind to one side of protein 2, plus a separate ability to bind to the opposite side of protein 2 (see Finnegan et al’s Figure 3). Thornton’s results are consistent with the idea that, by happenstance, the gene for protein 1 duplicated and spread in the population. (These events apparently were neutral, the authors think, not affecting the organism’s fitness.) Eventually one of the duplicates acquired a degradative mutation, losing the ability to bind one side of protein 2. This was not a problem because the second copy of the protein 1 gene was intact, and could bind both sides of protein 2, so a complete ring could still be formed. This also spread by neutral processes. As luck might have it, the second gene copy subsequently acquired its own degradative mutation, so that it could no longer bind the other side of protein 2. Again it’s no problem, however, because the first mutant copy of protein 1 could bind to the first side of protein 2, bind a few more copies of itself, then bind a copy of protein 3, which still had the ability to bind the other side of protein 2. So a closed, six-member ring could still be formed. This apparently also spread by neutral processes until it took over the entire kingdom of fungi.

The work of Finnegan et al (2012) strikes me as quite thorough and elegant. I have no reason to doubt that events could have unfolded that way. However, the implications of the work for unguided evolution appear very different to me then they’ve been spun in media reports. ( http://tinyurl.com/7lawgpl ) The most glaringly obvious point is that, like the results of Lenski’s work, this is evolution by degradation. All of the functional parts of the system were already in place before random mutation began to degrade them. Thus it is of no help to Darwinists, who require a mechanism that will construct new, functional systems. What’s more, unlike Lenski’s results, the mutated system of Thornton and colleagues is not even advantageous; it is neutral, according to the authors. Perhaps sensing the disappointment for Darwinism in the results, the title of the paper and news reports emphasize that the “complexity” of the system has increased. But increased complexity by itself is no help to life — rather, life requires functional complexity. One can say, if one wishes, that a congenitally blind man  teaming up with a congenitally legless man to safely move around the environment is an increase in “complexity” over a sighted, ambulatory person. But it certainly is no improvement, nor does it give the slightest clue how vision and locomotion arose.

Finnegan et al’s (2012) work intersects with several other concepts. First, their work is a perfect example of  Michael Lynch’s idea of “subfunctionalization”, where a gene with several functions duplicates, and each duplicate loses a separate function of the original. (Force et al, 1999) Again, however, the question of how the multiple functions arose in the first place is begged. Second, it intersects somewhat with the recent paper by Austin Hughes (2011) in which he proposes a non-selective mechanism of evolution abbreviated “PRM” (plasticity-relaxation-mutation), where a “plastic” organism able to survive in many environments settles down in one and loses by degradative mutation and drift the primordial plasticity. But again, where did those primordial functions come from? It seems like some notable workers are converging on the idea that the information for life was all present at the beginning, and life diversifies by losing pieces of that information. That concept is quite compatible with intelligent design. Not so much with Darwinism.

Finally, Thornton and colleagues latest work points to strong limits on the sort of neutral evolution that their own work envisions. The steps needed for the scenario proposed by  Finnegan et al (2012) are few and simple: 1) a gene duplication; 2) a point mutation; 3) a second point mutation. No event is deleterious. Each event spreads in the population by neutral drift. Notice that the two point mutations do not have to happen together. They are independent, and can happen in either order. Nonetheless, this scenario is apparently exceedingly rare. It seems to have happened a total of one (that is, 1) time in the billion years since the divergence of fungi from other eukaryotes. It happened only once in the fungi, and a total of zero times in the other eukaryotic branches of life. If the scenario were in fact as easy to achieve in nature as it is to describe in writing, we should expect it to have happened many times independently in fungi and also to have happened in all other branches of eukaryotes.

It didn’t. Thus it seems a good conclusion that such neutral scenarios are much rarer than some workers have proposed (Gray et al, 2010; Lukes et al, 2011), and that more complex neutral scenarios are unlikely to happen in the history of life.

Literature Cited

Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

Finnigan, G. C., V. Hanson-Smith, T. H. Stevens, and J. W. Thornton, 2012 Evolution of increased complexity in a molecular machine. Nature doi: 10.1038/nature10724.

Force, A., M. Lynch, F. B. Pickett, A. Amores, Y. L. Yan et al. 1999 Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151: 1531-1545.

Gray, M. W., J. Lukes, J. M. Archibald, P. J. Keeling, and W. F. Doolittle, 2010 Irremediable complexity? Science 330: 920-921.

Hughes, A. L., 2011 Evolution of adaptive phenotypic traits without positive Darwinian selection. Heredity (Edinb.) doi: 10.1038/hdy.2011.97.

Lukes, J., J. M. Archibald, P. J. Keeling, W. F. Doolittle, and M. W. Gray, 2011 How a neutral evolutionary ratchet can build cellular complexity. IUBMB Life 63: 528-537.

"They talk the language of science, but it is really a post-God religion that rejects relativist materialism."

-BBC reporter Michael Buerke

Podcast Transcription below the fold.

The Fifth Column –

Michael Buerk on the Climate Summit

The latest so-called Climate Summit, that’s been taking place in Durban, hasn’t made many waves. It could be because global warming seems less daunting if you can no longer afford heating bills. It could also be that we’re getting fed up with the bogus certainties and quasi-religious tone of the great climate change non-debate.

As with all religions, whether the underlying narrative is true, has become beside the point.”

– Michael Buerk, 16 Dec 2011

Trust is a pretty important factor that plays a positive role in a functioning society. To trust someone basically entails that you can rely on the actions of another person to conform to certain virtues or expectations while basically abandoning your own control over the situation.

Let’s look at two examples of where trust plays an important role. Firstly, you have money to do empirical research. You provide the money to a scientific researcher with a good track record and you ask him to do research on the clinical effects of a certain compound. You trust the scientist to use your money in such a manner that will result in good results. You are basically abandoning your own control over the situation (doing your own research) and transferring control to another. The outcome is unknown, but you trust that it will end in a certain manner i.e. good results.

Secondly, in a democratic society the voters vote for politicians whom they trust will do the job they want them to do. For example, if voters want a certain service and a political party makes certain promises and the voters like the promises and they vote for the party, then the voters are essentially abandoning their own control and transferring control to the party. Again, the outcome is unknown but the voters trust that the party leaders will stick to their word.

Now there are at least two ways to be a moral relativist. You can agree that different cultures have different moral values and that there is not a single universal moral that is shared by all cultures.  Call it “descriptive moral relativism”. You can also assert that there are no objectively and intrinsically good or evil actions. Call it “meta-ethical moral relativism”. Empirical data seems to suggest that descriptive moral relativism is true. It is however a logical fallacy to claim that this demonstrates that meta-ethical moral relativism is true. A person can be a descriptive moral relativist and not be a meta-ethical moral relativist.

There are also at least two ways to be a moral absolutist. The first way is to argue that if action X is absolutely and intrinsically morally wrong then action X is ALWAYS absolutely and intrinsically morally wrong. Call it “universal moral absolutism”. The second way is argue that if it is wrong for one person to commit act X in situation Z, then it is wrong for any person to commit act X in the same situation Z. The second view thus allows for a situation where action X in situation Z is wrong but is not absolutely and intrinsically wrong at different moments. Call it “situational moral absolutism”.

In what way can a person be trusted you may ask? Here again there are at least two ways to trust a person. One can trust a person based on reason and logic and one can trust a person in a manner that is not based on reason and logic. For example a person can trust another for emotional reasons, whatever they may be.  You can basically trust anything or any person in a manner that is not based on reason and logic. You can trust a wild lion that is chasing after you to not eat you because you may perhaps be emotionally attached to cats, or you can trust you’re a hijacker not to kill you because you think deep down he is a good person. To trust someone or something in a way that is not based on reason and logic is basically trusting a person or something on faith that is not grounded in any reason and logic. People of course do this all the time, it’s called blind faith.

Now the kind of moral relativism I wish to focus on in this entry is the one that denies both kinds of moral absolutism discussed and I want to know how any person can trust a meta-ethical moral relativist in a manner that is based on reason and logic?

Let’s get back to the two examples. Is there any way a person can logically trust a scientist to do good research (irrespective of his credentials) if he states that there are no objectively and intrinsically good or evil actions? Is there any way a voter can logically trust the promises of a person that states that there are no objectively and intrinsically good or evil actions?

In both of the above cases I would argue no and in general I don’t think there is a logical and rational way to trust a meta-ethical moral relativist. The moral beliefs of a meta-ethical moral relativist might be just what the voters or hos financial backers are looking for. He or she might believe individual rights are good, but he can’t believe they are objectively good, and does think it is only relatively bad and good. He might later on change his mind on any issue he supported, or lie about anything and still think his choices are relatively good and relatively bad. A meta-ethical moral relativist can basically lie, be corrupt and fake a very good personality, policies and empirical data and still feel morally superior to those who disapprove of his choices, even if he contradicts himself.

A few studies have now pointed out that atheists are among the most distrusted groups of people. I wonder whether this has something to do with how people may perceive atheists as meta-ethical moral relativists?

The main issue is how can you trust a meta-ethical moral relativist in such manner that does not collapse into blind faith that is not grounded in reason and logic?

In my comments on this interesting work ( http://tinyurl.com/3cjm4gr ), I noted that there is nothing time-asymmetric about random mutation/natural selection, so that the problem they saw in reversing the steroid hormone receptor evolution did not have to be in the past — it could just as easily have been in the future. The reason is that natural selection hones a protein to its present job, with regard to neither future use nor past function. Thus, based on Thornton’s work, one would not in general expect a protein that had been selected for one function to be easily modified by RM/NS to another function. I have decided to call this the Time-Symmetric Dollo’s Law, or “TSDL”.

But if there is such a thing as a TSDL, did the forward evolution of the steroid-hormone protein-receptor manage to avoid it? That question had not yet been addressed. Was the protein lucky this time, and encountered no obstacles to its evolution from the ancestral state to the modern state? If so, then maybe TSDL is occasionally an obstacle, but not so often as to rule out modest Darwinian evolution of proteins (as I had thought before reading Thornton’s earlier work).

Well, thanks to the Thornton group’s new work ( http://tinyurl.com/3dsorzm ), we can now see that there are indeed obstacles to the forward evolution of the ancestral protein. The group was interested in which of the many sequence changes between the ancestral and derived-modern protein were important to its change in activity, which consisted mostly of a considerable weakening of the protein’s ability to bind its steroid ligands. They narrowed the candidates down to two amino acid positions, residues 43 and 116. Each of the changes at those sites decreased binding by over a hundred-fold. However, when the researchers combined both mutations into a single protein, as occurs in the modern protein, binding was not only decreased — it was for all intents and purposes abolished. Upon further research the group showed that a third mutation, at position 71, was necessary to ameliorate the effects of the combination of the other two mutations, bringing them back to hundreds-fold loss of function rather than essentially-complete loss of function.

Carroll et al (2011) conjecture that the mutation at position 71 occurred before the other two mutations, but that it had no effect on the activity of the ancestral protein. So let us count the ways, then, in which “fortune” favored the evolution of the modern protein. First, an ancestral gene duplicated, which would usually be considered a neutral event. Thus it would not have the assistance of natural selection to help it spread in the population. Next, it avoided hundreds of possible mutations which would have rendered the duplicated gene inactive. Third, it acquired a neutral mutation at position 71. Thus, again, this mutation would have to spread by drift, without the aid of natural selection. Once more, the still-neutral gene manages to avoid all of the possible mutations that would have inactivated it. Next, it acquires the correct mutation (either at position 43 or 116) which finally differentiates it from its parent gene — by reducing its activity a hundred-fold! Finally, somehow the wimpy, mutated gene (putatively) confers upon the lucky organism some likely-quite-weak selective advantage.

The need for passage through multiple neutral steps plus the avoidance of multiple likely-deleterious steps to produce a protein that has lost 99% of its activity is not a ringing example of the power of Darwinian processes. Rather, as mentioned above, it shows the strength of TSDL. Darwinian selection will fit a protein to its current task as tightly as it can. In the process, it makes it extremely difficult to adapt to a new task or revert to an old task by random mutation plus selection.

Dollo’s law holds going forward as well as backward. We can state the experimentally based law simply: “Any evolutionary pathway from one functional state to another is unlikely to be traversed by random mutation and natural selection. The more the functional states differ, the much-less likely that a traversable pathway exists.”

1. Carroll, S. M., E. A. Ortlund, and J. W. Thornton, 2011 Mechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor. PloS. Genet. 7: e1002117.

2. Bridgham, J. T., E. A. Ortlund, and J. W. Thornton, 2009 An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461: 515-519.

The gist of the paper is this. The authors think that over evolutionary time, neutral processes would tend to “complexify” the cell. They call that theoretical process “constructive neutral evolution” (CNE). In an amusing analogy they liken cells in this respect to human institutions:

Organisms, like human institutions, will become ever more ”bureaucratic,” in the sense of needlessly onerous and complex, if we see complexity as related to the number of necessarily interacting parts required to perform a function, as did Darwin. Once established, such complexity can be maintained by negative selection: the point of CNE is that complexity was not created by positive selection. (1)

In brief, the idea is that neutral interactions evolve serendipitously in the cell, spread in a population by drift, get folded into a system, and then can’t be removed because their tentacles are too interconnected. It would be kind of like trying to circumvent the associate director of licensing delays in the Department of Motor Vehicles — can’t be done.

The possible problem the authors are trying to address is that they think many systems in the cell are needlessly complex. For example, the spliceosome, which “splices” some RNAs (cuts a piece out of the middle of a longer RNA and stitches the remaining pieces together), is a huge conglomerate containing “five small RNAs (snRNAs) and >300 proteins, which must be assembled de novo and then disassembled at each of the many introns interrupting the typical nascent mRNA.” (1) What’s more, some RNAs don’t need the spliceosome — they can splice themselves, without any assistance from proteins. So why use such an ungainly assemblage if a simpler system would do?

The authors think the evolution of such a complex is well beyond the powers of positive natural selection: “Even Darwin might be reluctant to advance a claim that eukaryotic spliceosomal introns remove themselves more efficiently or accurately from mRNAs than did their self-splicing group II antecedents, or that they achieved this by ‘numerous, successive, slight modifications’ each driven by selection to this end.” (1)

Well, I can certainly agree with them about the unlikelihood of Darwinian processes putting together something as complex as the spliceosome. However, leaving aside the few RNAs involved in the splicesome, I think their hypothesis of CNE as the cause for the interaction of hundreds of proteins — or even a handful — is quite implausible. (An essay skeptical of large claims for CNE, written from a Darwinian-selectionist viewpoint, has appeared recently (3) along with a response from the authors (4)).

The authors rationale for how a protein drifts into becoming part of a larger complex is illustrated by Figure 1 of their recent paper (similar to the single figure in their Science essay). A hypothetical “Protein A” is imagined to be working just fine on its own, when hypothetical “Protein B” serendipitously mutates to bind to it. This interaction, postulate the authors, is neutral, neither helping nor harming the ability of Protein A to do its job. Over the generations Protein A eventually suffers a mutation which would have decreased or eliminated its activity. However, because of the fact that Protein B is bound to it, the mutation does not harm the activity of Protein A. This is still envisioned to be a neutral interaction by the authors, and organisms containing the Protein A-Protein B complex drift to fixation in the population. Then other mutations come along, co-adapting the structures of Protein A and Protein B to each other. At this point the AB complex is necessary for the activity of Protein A. Repeat this process several hundred more times with other proteins, and you’ve built up a protein aggregate with complexity of the order of the spliceosome.

Is this a reasonable hypothesis? I don’t mean to be unkind, but I think that the idea seems reasonable only to the extent that it is vague and undeveloped; when examined critically it quickly loses plausibility. The first thing to note about the paper is that it contains absolutely no calculations to support the feasibility of the model. This is inexcusable. The mutation rates of various organisms — viral, prokaryotic, eukaryotic — are known to sufficient accuracy (5) that estimates of how frequently the envisioned mutations arrive could have been provided. The neutral theory of evolution is also well-developed (6), which would allow the authors to calculate how long it would take for the postulated neutral mutations to spread in a population. Yet no numbers — not even back-of-the-envelope calculations — are provided. Previous results by other workers (7-9) have shown that the development of serendipitous specific binding sites between proteins would be expected to be quite rare, and to involve multiple mutations. Kimura (6) showed that fixation of a mutation by neutral drift would be expected to take a looong time. Neither of these previous results bodes well for the authors’ hypothesis.

The second thing to notice about the paper is that there is no experimental support for its hypothesis. As the authors point out:

Development of in vitro experimental systems with which to test CNE will be an important step forward in distinguishing complex biology that arose due to adaptation versus nonadaptive complexity, as part of a larger view to understand the interplay between neutral and adaptive evolution, such as the intriguing long-term evolution experiments of Lenski and coworkers. (1)

Yet no such experimental evolutionary results have been reported to my knowledge, either by Lenski or by other workers (10).

Besides the lack of support from calculations or experiments, the authors discuss no possible obstacles to the scheme. I certainly understand that workers want to accentuate the positive when putting a new model forward, but potential pitfalls should be pointed out, so that other researchers have a clearer idea of the promise of the model before they invest time in researching it.

The first possible pitfall comes at the first step of the model, where a second protein is postulated to bind in a neutral fashion to a working protein. How likely is that step to be neutral? At the very least, we now have two proteins, A & B, that now have a large part of their surfaces obstructed that weren’t before. Will this interfere with their activities? It seems there is a good chance. Second, simply by Le Chatelier’s principle the binding of the two proteins must affect the free energies of their folded states. What’s more, the flexibility of both proteins must be affected. Will these individual effects serendipitously cancel out so that the overall effect will be neutral? It seems like an awful lot to ask for without evidence.

In the next step of the model Protein A is supposed to suffer a mutation that would have caused it to lose activity, but, luckily, when it is bound to Protein B it is stabilized enough so that activity is retained. What fraction of possible mutations to Protein A would fall in that range? It seems like a very specialized subfraction. Looking at the flip side, what fraction of mutations to Protein A and/or Protein B which otherwise would not have caused A to lose activity will now do so because of its binding to Protein B?

The last step of the model is the “co-adaptation” of the two proteins, where other, complementary mutations occur in both proteins. Yet this implies that the protein complex must suffer deleterious mutations at least every other step, provoking the “co-adaptive” mutation to fix in the population. Wouldn’t these deleterious mutations be very unlikely to spread in the population?

Finally, multiply these problems all by a hundred to get a spliceosome. Or, rather, raise these problems to the hundredth power. But, then, why stop at a hundred? As the authors note approvingly:

Indeed, because CNE is a ratchet-like process that does not require positive selection, it will inevitably occur in self-replicating, error prone systems exhibiting sufficient diversity, unless some factor prevents it. (1)

Why shouldn’t the process continue, folding in more and more proteins, until the cell congeals? I suppose the authors would reply, “some factor prevents it”. But might not that factor kick in at the first or second step? The authors give us no reason to think it wouldn’t.

The CNE model (at least on the scale envisioned by the authors) faces other problems as well (for example, it would be a whole lot easier to develop binding sites for metal ions or metabolites that are present in the cell at much higher concentrations than most proteins), but I think this is enough to show it may not be as promising as the article would have one believe.

Besides the model itself, it is interesting to look at a professed aspect of the motivation of the authors in proposing it. It may not have escaped your notice, dear reader, that “irremediable complexity” sort of sounds like “irreducible complexity”. In fact, the authors put the model forward as their contribution to the good fight against “antievolutionists”:

… continued failure to consider CNE alternatives impoverishes evolutionary discourse and, by oversimplification, actually makes us more vulnerable to critiques by antievolutionists, who like to see such complexity as ”irreducible.” (1)

So there you have it. The authors don’t think Darwin can explain such complexity as is found in the proteasome, and they apparently rule out intelligent design. (By the way, when will these folks ever grasp the fact that intelligent design is not “antievolution”?) “Irremediable complexity” seems to be all that’s left, no matter how unsupported and problematic it may be.

Although the authors seem not to notice, their entire model is built on a classic argument from ignorance, beginning with the definition of irremediable complexity:

”irremediable complexity”: the seemingly gratuitous, indeed bewildering, complexity that typifies many cellular subsystems and molecular machines, particularly in eukaryotes. (1)

“Seemingly gratuitous”. In other words, the authors don’t know of a function for the complexity of some eukaryotic subsystems; therefore, they don’t have functions. Well the history of arguments asserting that something or other in biology is functionless is pretty grim. More, the history of assertions that even “simple” things (like, say, DNA, pre-1930) in the cell either don’t have a function or are just supporting structures is abysmal. Overwhelmingly, progress in biology has consisted of finding new and ever-more-sophisticated properties of systems that had been thought simple. If apparently simple systems are much more complex than they initially seemed, I would bet heavily against the hypothesis that apparently complex systems are much simpler than they appear.

References

1.  Lukes, J., J. M. Archibald, P. J. Keeling, W. F. Doolittle, and M. W. Gray, 2011 How a neutral evolutionary ratchet can build cellular complexity. IUBMB Life 63: 528-537.

2.  Gray, M. W., J. Lukes, J. M. Archibald, P. J. Keeling, and W. F. Doolittle, 2010 Cell biology. Irremediable complexity? Science 330: 920-921.

3.  Speijer, D., 2011 Does constructive neutral evolution play an important role in the origin of cellular complexity? Making sense of the origins and uses of biological complexity. Bioessays 33: 344-349.

4.  Doolittle, W. F., J. Lukes, J. M. Archibald, P. J. Keeling, and M. W. Gray, 2011 Comment on “Does constructive neutral evolution play an important role in the origin of cellular complexity?” Bioessays 33: 427-429.

5.  Drake, J. W., B. Charlesworth, D. Charlesworth, and J. F. Crow, 1998 Rates of spontaneous mutation. Genetics 148: 1667-1686.

6.  Kimura M., 1983 The neutral theory of molecular evolution. Cambridge University Press, Cambridge.

7.  Nissim, A., H. R. Hoogenboom, I. M. Tomlinson, G. Flynn, C. Midgley, D. Lane, and G. Winter, 1994 Antibody fragments from a ’single pot’ phage display library as immunochemical reagents. EMBO Journal 13: 692-698.

8.  Griffiths, A. D., S. C. Williams, O. Hartley, I. M. Tomlinson, P. Waterhouse, W. L. Crosby, R. E. Kontermann, P. T. Jones, N. M. Low, T. J. Allison, and G. Winter, 1994 Isolation of high affinity human antibodies directly from large synthetic repertoires. EMBO Journal 13: 3245-3260.

9.  Smith, G. P., S. U. Patel, J. D. Windass, J. M. Thornton, G. Winter, and A. D. Griffiths, 1998 Small binding proteins selected from a combinatorial repertoire of knottins displayed on phage. Journal of Molecular Biology 277: 317-332.

10.  Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

The term “evolvability” has been used widely and rather loosely in the literature for the past few decades. It usually means something like the following: a species possesses some biological feature which lends itself to evolving more easily than other species that don’t possess the feature, so that the lucky species will tend to adapt and survive better than its rivals over time. The kind of feature that is most often invoked in this context is “modularity.” That word itself is often used in a vague manner. As I wrote in The Edge of Evolution, “Roughly, a module is a more-or-less self-contained biological feature that can be plugged into a variety of contexts without losing its distinctive properties. A biological module can range from something very small (such as a fragment of a protein), to an entire protein chain (such as one of the subunits of hemoglobin), to a set of genes (such as Hox genes), to a cell, to an organ (such as the eyes or limbs of Drosophila).” (3)

Well, Lenski and co-workers don’t use “evolvability” in that sense. They use the term in a much broader sense: “Evolutionary potential, or evolvability, can be operationally defined as the expected degree to which a lineage beginning from a particular genotype will increase in fitness after evolving for a certain time in a particular environment.” (1) To put it another way, in their usage “evolvability” means how much an organism will increase in fitness over a defined time starting from genotype A versus starting from genotype B, no matter whether genotypes A and B have any particular identifiable feature such as modularity or not.

Lenski’s group published a very interesting paper last year showing that the more defective a starting mutant was in a particular gene (rpoB, which encodes a subunit of RNA polymerase), the more “evolvable” it was. (2) That is, more-crippled cells could gain more in fitness than less-crippled cells. But none of the evolved crippled cells gained enough fitness to match the uncrippled parent strain. Thus it seemed that more-crippled cells could gain more fitness simply because they started from further back than less-crippled ones. Compensatory mutations would pop up somewhere in the genome until the evolving cell was near to its progenitor’s starting point. This matches the results of some viral evolution studies where some defective viruses could accumulate compensatory mutations until they were similar in fitness to the starting strain, whether they began with one-tenth or one-ten-billionth of the original fitness. (4)

In a paper published a few weeks ago the Michigan State group took a somewhat different experimental tack. (1) They isolated a number of cells from relatively early in their long-term evolution experiment. (Every 500^th generation during the 50,000-generation experiment Lenski’s group would freeze away the portion of the culture which was left over after they used a part of it to seed a flask to continue the growth. Thus they have a very complete evolutionary record of the whole lineage, and can go back and conduct experiments on any part of it whenever they wish. Neat!) They saw that different mutations had cropped up in different early cells. Interestingly, the mutations which gave the greatest advantage early on had become extinct after another 1,000 generations. So Lenski’s group decided to investigate why the early very-beneficial mutations were nonetheless not as “evolvable” (because they were eventually outcompeted by other lineages) as cells with early less-beneficial mutations.

The workers examined the system thoroughly, performing many careful experiments and controls. (I encourage everyone to read the whole paper.) The bottom line, however, is that they found that changing one particular amino acid residue in one particular protein (called a “topoisomerase”, which helps control the “twistiness” of DNA in the cell), instead of a different amino acid residue in the same protein, interfered with the ability of a subsequent mutation in a gene (called spoT) for a second protein to help the bacterium increase in fitness. In other words, getting the “wrong” mutation in topoisomerase — even though that mutation by itself did help the bacterium — prevented a mutation in spoT from helping. Getting the “right” mutation in topoisomerase allowed a mutation in spoT to substantially increase the fitness of the bacterium.

The authors briefly discuss the results (the paper was published in Science, which doesn’t allow much room for discussion) in terms of “evolvability”, understood in their own sense. (1) They point out that the strain with the right topoisomerase mutation was more “evolvable” than the one with the wrong topoisomerase mutation, because it outcompeted the other strain. That is plainly correct, but does not say anything about “evolvability” in the more common and potentially-much-more-important sense of an organism possessing modular features that help it evolve new systems. “Evolvability” in the more common sense has not been tested experimentally in a Lenski-like fashion.

In my own view, the most interesting aspect of the recent Lenski paper is its highlighting of the pitfalls that Darwinian evolution must dance around, even as it is making an organism somewhat more fit. (1) If the “wrong” advantageous mutation in topoisomerase had become fixed in the population (by perhaps being slightly more advantageous or more common), then the “better” selective pathway would have been shut off completely. And since this phenomenon occurred in the first instance where anyone had looked for it, it is likely to be commonplace. That should not be surprising to anyone who thinks about the topic dispassionately. As the authors note, “Similar cases are expected in any population of asexual organisms that evolve on a rugged fitness landscape with substantial epistasis, as long as the population is large enough that multiple beneficial mutations accumulate in contending lineages before any one mutation can sweep to fixation.” If the population is not large enough, or other factors interfere, then the population will be stuck on a small peak of the rugged landscape.

This fits well with recent work by Lenski’s and others’ laboratories, showing that most beneficial mutations actually break or degrade genes (4), and also with work by Thornton’s group showing that random mutation and natural selection likely could not transform a steroid hormone receptor back into its homologous ancestor, even though both have very similar structures and functions, because the tortuous evolutionary pathway would be nearly impossible to traverse. (5, 6) The more that is learned about Darwin’s mechanism at the molecular level, the more ineffectual it is seen to be.

1. Woods, R. J., J. E. Barrick, T. F. Cooper, U. Shrestha, M. R. Kauth, and R. E. Lenski.  2011 Second-order selection for evolvability in a large Escherichia coli population. Science 331: 1433-1436.

2. Barrick, J. E., M. R. Kauth, C. C. Strelioff, and R. E. Lenski, 2010 Escherichia coli rpoB mutants have increased evolvability in proportion to their fitness defects. Molecular Biology and Evolution 27: 1338-1347.

3. Behe M. J., 2007 The Edge of Evolution: the search for the limits of Darwinism. Free Press, New York.

4. Behe, M. J., 2010 Experimental Evolution, Loss-of-function Mutations, and “The First Rule of Adaptive Evolution”. Quarterly Review of Biology 85: 1-27.

5. Bridgham, J. T., E. A. Ortlund, and J. W. Thornton, 2009 An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461: 515-519.

6. See my comments on Thornton’s work at the middle of http://behe.uncommon descent.com/page/2/ and the bottom of http://behe.uncommondescent.com/.

Try as one might to keep Darwinists focused on the data, some can’t help reverting to their favorite trope: questioning Darwinism simply must be based on religion. Unfortunately Professor Coyne succumbs to this. Introducing his blog post he writes:

What role does the appearance of new genes, versus simple changes in old ones, play in evolution? There are two reasons why this question has recently become important…. The first involves a scientific controversy…. The second controversy is religious. Some advocates of intelligent design (ID)—most notably Michael Behe in a recent paper—have implied not only that evolved new genes or new genetic “elements” (e.g., regulatory sequences) aren’t important in evolution, but that they play almost no role at all, especially compared to mutations that simply inactivate genes or make small changes, like single nucleotide substitutions, in existing genes. This is based on the religiously-motivated “theory” of ID, which maintains that new genetic information cannot arise by natural selection, but must installed [sic] in our genome by a magic poof from Jebus. [sic]

Anyone who reads the paper, however, knows my conclusions were based on the reviewed experiments of many labs over decades. Even Coyne knows this. In the very next sentence he writes, schizophrenically, “I’ve criticized Behe’s conclusions, which are based on laboratory studies of bacteria and viruses that virtually eliminated the possibility of seeing new genes arise, but I don’t want to reiterate my arguments here.” Yet if my conclusions are based on “laboratory studies”, then they ain’t “religious”, even if Coyne disagrees with them.

Professor Coyne is so upset, he imagines things that aren’t in the paper. (They are “implied”, you see.) So although I haven’t actually written it, supposedly I have “implied not only that evolved new genes or new genetic ‘elements’ … aren’t important in evolution, but that they play almost no role at all….” [Coyne’s emphasis]

“Play almost no role at all”? When I first read these “implied” words that Coyne wants to put in my mouth, I thought the argumentative move rang a bell. Sure enough, check out the Dilbert comic strip from November 1, 2001 (http://tinyurl.com/6y6upgc), where Dilbert complains that a co-worker “changed what I said into a bizarre absolute.” If one person says that an event is “very unlikely”, and an interlocutor rephrases that into “so, you say it’s logically impossible and would never happen even in an infinite multiverse”, well then, the second fellow is setting up a straw man.

Contrast Coyne’s imagined “implications” with what I actually wrote in the review. Considering possible objections to my conclusions I noted that:

A third objection could be that the time and population scales of even the most ambitious laboratory evolution experiments are dwarfed when compared to those of nature. It is certainly true that, over the long course of history, many critical gain-of-FCT events occurred. However, that does not lessen our understanding, based upon work by many laboratories over the course of decades, of how evolution works in the short term, or of how the incessant background of loss-of-FCT mutations may influence adaptation.

Although I think that statement is clear enough in the context of the paper, let me say it differently in case some folks are confused. Loss of function mutations occur relatively rapidly, and LOF mutations can be adaptive. Gain of function mutations can be adaptive, too, but their rate of occurrence (including the rate of gene duplication-plus-divergence that Coyne is discussing) is much less. Thus whenever a new selective pressure pops up, LOF adaptive mutations (if such there be in the particular circumstance) can appear most swiftly, and will likely dominate short-term adaptation. So when a GOF mutation eventually appears, it will likely be against the altered genetic background of the selective pressure ameliorated by the adaptive LOF mutation(s). In order to understand how evolution works in the long term, we must take that into consideration.

Professor Coyne notes that the new genes studied by Professor Long “arise quickly, at least on an evolutionary timescale”. [my emphasis] But adaptive LOF mutations arise quickly even on a laboratory timescale. For example, as I note in my QRB review, in one experiment (http://tinyurl.com/4zyxt66) adaptive mutations in E. coli cultures due to loss of function mutations in the rpoS gene “occurred, and indeed spread at rapid rates within a few generations of establishing glucose-limited chemostats”. A few generations for E. coli can be on the order of hours. The gene duplications studied by Professor Long occur on the order of millions of years. Admittedly the situation in nature is more complex than in the laboratory. Nonetheless, whatever selective pressures the gene duplications encounter when they eventually show up will already have been substantially altered by adaptive LOF mutations. That’s a very important point for evolutionary biologists to keep in mind.

I have never stated, nor do I think, that gene duplication and diversification cannot happen by Darwinian mechanisms, or that “they play almost no role at all” in the unfolding of life. (As a matter of fact, I discussed several examples of that in my 2007 book The Edge of Evolution. (http://tinyurl.com/4nqxhvr)) That would be silly — why would anyone with knowledge of basic biochemical mechanisms deny that, say, the two gamma-globin coding regions on human chromosome 11 resulted from the duplication of a single gamma-globin gene and then the alteration of a single codon? What I don’t think can happen is that duplication/ divergence by Darwinian mechanisms can build new, complex interactive molecular machines or pathways. Assuming (since he is in fact critiquing them) Professor Coyne has been attentive to my arguments, one background assumption that he may have left unexpressed is that he thinks the newer duplicated genes discovered by Professor Long’s excellent work represent such complex entities, or parts of them.

There is no reason to think so. A gene can duplicate and diversify without building a new machine or network, or even changing function much. The above example of the two gamma-globin genes shows that duplication does not necessarily result in change in function. The examples of delta- and epsilon-globin, which, like gamma-globin, presumably also resulted from the duplication of an ancestral beta-like globin gene, show that sequence can diversify further, but function remain very similar. Even myoglobin, which shares rather little sequence homology with the other globins, has not diverged much in biochemical function.

In his recent work Professor Long discovered that many of the new genes were essential for the viability of the organism — without the gene product, the fruitflies would die before maturity. Perhaps Professor Coyne thinks that that means the genes necessarily are parts of complex systems, or at least do something fundamentally new. Again, however, there is no reason to think so. The notion of “essential” genes is at best ambiguous. We know of examples of proteins that surely appear necessary, but whose genes are dispensable. The classic example is myoglobin (http://tinyurl.com/4ogmd98). It is also easy to conceive of a simple route to an “essential” duplicate gene that does little new. Suppose, for example, that some gene was duplicated. Although the duplication caused the organism to express more of the protein than was optimum, subsequent mutations in the promoter or protein sequence of one or both of the copies decreased the total activity of the protein to pre-duplication levels. Now, however, if one of the copies is deleted, there is not enough residual protein activity for the organism to survive. The new copy is now “essential”, although it does nothing that the original did not do.

To sum up, the important point of “Experimental Evolution, Loss-of-Function Mutations, and ‘The First Rule of Adaptive Evolution’” (http://tinyurl.com/25c422s) is not that anything in particular in evolution is absolutely ruled out. Rather, the point is that short term adaptation tends to be dominated by LOF mutations. And, tinkerer that it is, Darwinian evolution always works in the short term.

Here’s an analogy that some people might find amusing and helpful. Think of GOF mutations (such as the gene duplication/divergence that Professor Coyne discusses) as the “snail mail” of evolution. And think of LOF mutations as the email, texting, and phone calls of evolution. In a busy world, by the time a real letter shows up at someone’s or some business’s door, a lot of communication concerning the subject of the slow letter would already have happened by faster means, and the more important the topic, the more fast-communication there likely would have been. That speedy communication can quite easily change the context of the letter, and either render it moot or at least less important. It is certainly possible that on occasion the slow letter will arrive with its impact unaffected by other messages, but it would be foolish to ignore the effect of the fast channels of communication.

Prof. Bull states that bacteriophage T7 (which he used in his studies) avoids taking up DNA from its host, E. coli, so it really isn’t an example of a system where novel DNA was available to the phage, despite his initial hopes that it would be. (In the paper describing the work he and his co-authors wrote, “At the outset, our expectation from work in other viral systems was that the loss of ligase activity would … require the [T7] genome to acquire new sequences through recombination or gene duplication.”) But, he writes in his new post, “what we failed to point out in our paper, and is fatal to MB’s criticism, is the fact that T7 degrades E. coli DNA, so even if the phage did incorporate an E. coli gene, it might well destroy itself in the next infection.” This reasoning strikes me as overlooking an obvious problem, and overlooking an obvious solution to the problem.

First, the problem. If T7, and presumably other bacteriophages, find it advantageous to have a mechanism that excludes host DNA from being incorporated into the phage genome, doesn’t this drastically cut down the opportunity for the very mixing of cross-species DNA that Coyne and Bull tout as the Darwinian solution to the problem of developing complex new functions? I suppose they could respond that, well, maybe the phages can’t exclude other, non-host DNA, so that’s where novel DNA would come from. But it seems host DNA would be by far the DNA the phages contacted the most. But if that is essentially excluded as a source, then the sorts of compensatory mutations that Professor Bull observed in his experiments are still by far the most likely ones to occur in nature. (And the grant application is saved!) It’s a matter of rate. The adaptive mutations that come along first will be selected first, and clearly point mutations and deletions come along very rapidly in phage populations.

Next, the solution. If a phage has a mechanism that is preventing it from taking up DNA that could be advantageous to it (such as the gene for a DNA ligase in the case of the experiment of Rokyta et al 2002 (http://tinyurl.com/3adlq6c)) then all it has to do is break that mechanism and the opportunity for acquiring DNA is now opened to it. After all, breaking things is what random mutation does best, and, as I reviewed, many of the reported adaptive mutations in lab evolution experiments resulted from broken genes. Broken genes can also be neutral mutations. In the majority of the cultures of E. coli that Richard Lenski has grown for 50,000 generations, “mutator” strains took over. A mutator strain is one which has lost at least part of its ability to repair its DNA. If E. coli can toss out part of its repair ability with impunity, why couldn’t T7 lose its inability to take up some helpful host DNA?

Professor Bull suggests (http://tinyurl.com/2cyetm7) that lab evolution experiments which use whole cells and viruses aren’t needed to show the power of Darwinian processes because that is apparent in experiments using “directed” evolution. I strongly disagree with his assessment. In directed evolution workers use an experimental set-up so that a single, particular gene or protein must mutate to be adaptive. “Directed” evolution is a much, much more artificial system than ones that use whole cells and/or viruses, as he did. In response to some selective pressure, a cell has potentially very many more ways to adapt to deal with it than does a single protein — a cell has thousands of genes and thousands of regulatory elements that can potentially help the cell adapt by gain- or loss-of-function, or tweaking of pre-existing function. On the other hand, directed evolution artificially constrains the system to mutate the component that the experimenter chooses. It seems a bit inconsistent to me for someone to claim that single species of cells (and/or viruses) are insufficiently complex to produce gain-of-function mutations by Darwinian processes, but that artificially constraining mutation/selection to single genes or proteins shows it clearly. Seems to me this is exactly backwards.

In his post (http://tinyurl.com/2cyetm7) Professor Bull describes an experiment (http://tinyurl.com/38qhow9) he did with coworkers which, they hoped, would mimic the process of gene duplication and divergence. They placed two copies of the same gene, each on its own kind of plasmid, into the same cell. The gene produced a protein that could disable one kind of antibiotic very well, and disable a second kind of antibiotic rather poorly. In the presence of both antibiotics, they expected one of the copies of the gene to stay about the same, degrading the first antibiotic. They expected the second copy of the gene to accumulate point mutations which would help it become more efficient at degrading the second kind of antibiotic (from other publications such mutants were already known to exist.) The system, however, had its own ideas. Bull says that contrary to expectations, one of the genes was deleted and the other gene accumulated point mutations so that it did a decent job degrading both antibiotics.

Professor Bull writes (http://tinyurl.com/2cyetm7) that, “This study merely illustrates that the conditions favoring the maintenance of two copies undergoing evolutionary divergence are delicate.” Skeptic that I am, instead of “delicate”, I would say it illustrates that the conditions are “rare”. That is, it demonstrates very nicely that having two copies of a gene under what seem to be ideal conditions for adaptive divergence is not enough. (A similar result using a different system was recently obtained by Gauger et al 2010 (http://tinyurl.com/2uc6d8g).) Other factors enter into the result as well. Since we don’t know exactly what those other factors are, or how rare they make successful duplication/divergence events, we should not automatically assume that the occurrence of duplicated and diverged genes in nature happened by unguided, Darwinian processes.

First, the nice thing. About half-way through his comments Professor Coyne writes:

My overall conclusion: Behe has provided a useful survey of mutations that cause adaptation in short-term lab experiments on microbes (note that at least one of these—Rich Lenski’s study— extends over several decades).

Thanks. Much appreciated.

Next, he turns to damage control. Directly after the mild compliment, Coyne registers his main complaint about the paper: the conclusions supposedly can only be applied to laboratory evolution experiments, and say little about (Darwinian) evolution in nature. “But his conclusions may be misleading when you extend them to bacterial or viral evolution in nature, and are certainly misleading if you extend them to eukaryotes (organisms with complex cells), for several reasons”. Below I deal with Coyne’s three reasons in turn.

Professor Coyne’s first objection is:

1. In virtually none of the experiments summarized by Behe was there the possibility of adapting the way that many bacteria and viruses actually adapt in nature: by the uptake of DNA from other microbes. Lenski’s studies of E. coli, for instance, and Bull’s work on phage evolution, deliberately preclude the presence of other species that could serve as vectors of DNA, and thus of new FCTs.

Coyne is simply wrong here, at least about phages (bacterial viruses). Viruses grow in other organisms — the cells they infect. Thus pretty much by definition they are in contact with other microbes for much of their life cycle, and it is thought that sometimes viruses acquire genes from their host cells. In fact, in one report by Bull’s group (http://tinyurl.com/3adlq6c) I reviewed, in which the gene for bacteriophage T7 ligase was intentionally removed at the start of an experiment, the investigators reported they initially expected the missing gene to be replaced.

At the outset, our expectation from work in other viral systems was that the loss of ligase activity would remain so deleterious to T7 that recovery to high fitness would require the genome to acquire new sequences through recombination or gene duplication and to replace ligase function by divergence of those sequences.

Unexpectedly, however, “This hope was not realized, and compensatory evolution occurred through point mutations and a deletion.” Thus it seems that Professor Coyne’s expectations about what is required for a gain-of-FCT event are not universally shared among scientists.

Coyne is of course correct that in experiments in which just one species of bacteria is present, the cells cannot acquire DNA from other species of bacteria. Yet those who conducted such experiments often had expectations for evolution much different from him. In the 1970’s and 1980’s many workers thought that gene duplication or recruitment plus divergence would allow bacteria to diversify the foodstuffs they could metabolize. Out of many such experiments, only one seemed to work by gain-of-FCT. Professor Coyne’s dismissal of such experiments is pure hindsight.

Professor Coyne doesn’t mention that in the review I argue that results from nature are consonant with conclusions drawn from lab experiments. I wrote:

One objection might be that the above examples are artificial. They concern laboratory evolution…. Nonetheless, results arguably similar to those that have been seen in laboratory evolution studies to date have also been seen in nature, such as the loss of many genes by Yersinia pestis (after, of course, the acquisition of new genetic material in the form of several plasmids), and the loss-of-FCT mutations that have spread in human populations in response to selective pressure from malaria. A tentative conclusion suggested by these results is that the complex genetic systems that are cells will often be able to adapt to selective pressure by effectively removing or diminishing one or more of their many functional coded elements.

Coyne’s second objection is the following:

2. In relatively short-term lab experiments there has simply not been enough time to observe the accumulation of complex FCTs, which take time to build or acquire from a rare horizontal transmission event.

I addressed that very point in my review:

Furthermore, although complex gain-of-FCT mutations likely would occur only on long time-scales unavailable to laboratory studies, simple gain-of-FCT mutations need not take nearly as long. As seen in Table 1, a gain-of-FCT mutation in sickle hemoglobin is triggered by a simple point mutation, which helps code for a new protein binding site. It has been estimated that new transcription-factor binding sites in higher eukaryotes can be formed relatively quickly by single point mutations in DNA sequences that are already near matches (Stone and Wray 2001). In general, if a sequence of genomic DNA is initially only one nucleotide removed from coding for an adaptive functional element, then a single simple point mutation could yield a gain-of-FCT. As seen in Table 5, several laboratory studies have achieved thousand- to million-fold saturations of their test organisms with point mutations, and most of the studies reviewed here have at least single-fold saturation. Thus, one would expect to have observed simple gain-of-FCT adaptive mutations that had sufficient selective value to outcompete more numerous loss-of-FCT or modification-of-function mutations in most experimental evolutionary studies, if they had indeed been available.

Yes, complex gain-of-FCT events would not be expected to occur, but simple GOF’s would. Yet they didn’t show up.

Professor Coyne then proceeds to put words in my mouth:

What [Be]he’s saying is this: “Yes, gain of FCTs could, and likely is, more important in nature than seen in these short-term experiments. But my conclusions are limited to these types of short-term lab studies.”

No, that is not what I was saying at all. I was saying that, no matter what causes gain-of-FCT events to sporadically arise in nature (and I of course think the more complex ones likely resulted from deliberate intelligent design http://tinyurl.com/32n64xl), short-term Darwinian evolution will be dominated by loss-of-FCT, which is itself an important, basic fact about the tempo of evolution.

Above I quoted Coyne talking about “complex FCTs, which take time to build or acquire from a rare horizontal transmission event”. Yet cells aren’t going to sit around twiddling their thumbs until that rare event shows up. Any mutation which confers an advantage at any time will be selected, and the large majority of those in the short term will be LOF. Ironically, Coyne seems to underestimate the power of natural selection, which “is daily and hourly scrutinising, throughout the world, every variation, even the slightest….” A process which scrutinizes life “daily and hourly”, as Darwin wrote, isn’t going to wait around for some rare event.

Professor Coyne’s third objection is:

3. Finally, Behe does not mention—and I think he should have—the extensive and very strong evidence for adaptation via gain-of-FCT mutations in eukaryotes.

As I show in Table 1 of the review, we have wonderful evidence of what Darwinian evolution has done to a multicellular eukaryotic species — Homo sapiens — in response to strong selective pressure from malaria over the past ten thousand years. A handful of mutations have been selected. The mutations are classified as: one GOF (the sickle mutation); two modification of functions; and five LOFs. That’s pretty much the proportion of what one sees in bacteria and larger viruses, so there is no reason to think that short-term evolution in eukaryotes has a substantially different spectrum of adaptive mutations than for prokaryotes.

Coyne wants to focus on long-term evolution:

While [eukaryotes] may occasionally acquire genes or genetic elements by horizontal transfer, we know that they acquire new genes by the mechanism of gene duplication and divergence: new genes arise by duplication of old ones, and then the functions of these once-identical genes diverge as they acquire new mutations. … Think of all the genes that have arisen in eukaryotes in this way and gained novel function: classic examples include genes of the immune system, Hox gene families, olfactory genes, and the globin genes.

Unfortunately, Professor Coyne isn’t making a critical distinction here. While we may know (or at least have very good evidence that is consonant with the idea) that new genes have arisen by duplication and divergence of old ones in eukaryotes, we do not know that happens by a Darwinian mechanism of random mutation and natural selection. And if some duplicate genes do arise and diversify by Darwinian processes, we do not know that explains all or even most of them. After all, while the long-term processes that Professor Coyne envisions are taking their sweet time to come together, the fast and dirty short-term adaptive processes will dominate. That’s what we know from the great efforts put into experimental evolutionary studies by many investigators over decades.

And as I point out in the QRB paper, all of this can be neatly summarized by The First Rule of Adaptive Evolution: Break or blunt any functional coded element whose loss would yield a net fitness gain.

For most of history such a question could not be investigated, but with the tools that have become available to molecular biology in the past few decades, a good start can be made on addressing it. The gist of the paper is that so far the overwhelming number of adaptive (that is, helpful) mutations seen in laboratory evolution experiments are either loss or modification of function. (I make a number of distinctions defining gain-, loss- and modification of function mutations, so for the complete story please read the paper.) Of course we had already known that the great majority of mutations that have a visible effect on an organism are deleterious. Now, surprisingly, it seems that even the great majority of helpful mutations degrade the genome to a greater or lesser extent.

Although the data reviewed are mostly from laboratory experiments, there are good reasons to think that the same situation would hold for Darwinian evolution in nature, too, as I discuss in the paper. From the data I propose a rule of thumb that could help guide researchers in their expectations of what they will find much of the time in studies of evolutionary adaptation. I dub it “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain.