Regulating the Regulators: A Single Arginine Insertion in the Glucocorticoid Receptor Changes Protein Expression

Damage Control Underway

Not only is evolution a fact beyond all reasonable doubt, it also is essential to ones understanding of biology. Indeed, without evolution, science itself would be impossible. These are the pronouncements of evolutionists who even go so far as to define life as the ability to evolve. Given these truths one would think that evolutionary theory would be rather important for research in the life sciences. Is not the evolutionary framework a necessary starting point? Surprisingly scientific progress consistently is made without evolution leading the way or even pointing in the right direction. Often evolutionists are surprised by the science and new evolutionary explanations are tacked on after the fact rather than providing the initial insight. Other times evolution simply is not even mentioned as it simply makes no sense on the science.

Consider, for example, transcription factors—proteins that influence and control the transcription of genes, which leads to the synthesis of new proteins. Evolution cannot explain how these genetic regulators evolved, and even if they did somehow evolve they don’t fit the expected evolutionary pattern.

But that’s only the beginning. Transcription factors operate according to instructions and codes that also don’t fit the evolutionary pattern, and their mechanisms are incredibly complex, including secondary regulation where a transcription factor influences a different transcription factor. You can read more about these marvels here, here and here.

Now new research on the glucocorticoid receptor—a transcription factor that, for example, helps to activate sugar production in the liver—presents yet more contradictions to evolutionary theory.

The glucocorticoid receptor has several components, one of which is a lever arm. After the glucocorticoid receptor gene is transcribed (a process that is influenced by yet other transcription factors), the messenger RNA transcript can be edited to produce different versions of the glucocorticoid receptor protein. In one such version a single arginine amino acid is inserted into the lever arm region. This single modification influences both how the different glucocorticoid receptor components communicate, and what types of DNA sequences the glucocorticoid receptor is likely to bind to. The result of all this is a change in the genes which are regulated and the magnitude of their regulation.

The editing machinery that inserts the single arginine amino acid is incredibly complicated. Under evolution we would have to believe that random mutations just happened to construct the fantastic editing machinery, a feat for which there is no explanation.

But evolution would have to repeat these heroics a large number of times to search through the astronomical number of different edits that are possible. How many amino acids should be edited? Should they be deleted or added? Which amino acids should be used? On which gene transcripts should the editing be performed? And where in the transcript should the edit be made?

And how did the evolutionists respond to these findings? In spite of the fact that this arginine insertion edit occurs in widespread species, they wonder if the whole operation isn’t just a mistake. A simple consequence of erroneous editing that is tolerated.

This is always the first guess of evolutionary theory. For if all of biology spontaneously arose via chance events, then we should expect to find a collection of broken or barely functional designs. But in the inexorable march of science, such assumptions are inevitably found to be false. Functional reasons are discovered, ascribed to evolution’s natural selection, and then it is on to the next finding which is assumed to be yet another erroneous design because, after all, evolution is a fact.

Evolutionists Are Celebrating a New Chimp-Human Study That Actually Just Presents More Problems

They Just Aren’t That Smart

Remember how nearly-identical chimpanzee-human genes were celebrated as yet another proof of evolution? There was only one problem: it didn’t make sense because the genes were too similar. The minor differences were probably not enough to produce species as different as the chimp and human and, as I explained in my book Darwin’s Proof, there must be more significant differences to be found between the two primates. And indeed such differences were discovered. One was that even those highly similar genes were often transcribed at very different levels in the two species. This, evolutionists reasoned, must have been a driver in the primate evolution that led to such different species. What evolutionists did not realize was that, once again, they had violated Occam’s Razor by adding yet more serendipity to their theory. With evolution we were to believe that essentially all the genes needed to make humans evolved first and then later the quantities were adjusted to evolve homo sapiens. Imagine an inventor who just luckily builds all the parts of a Boeing 747 but not in the right quantities. He has only one wing, three rudders, a dozen jet engines, and so forth. Then he realizes how well the parts work together if he merely adjusts the quantities a bit. Now a new study shows another problem with evolution’s just-so story of human evolution.

The new study shows that the differing transcription levels in chimps and humans do not correlate very well to differing protein expression levels. In other words, a gene may be copied more or less frequently, but that does not necessarily mean the resulting protein will be produced at higher or lower amounts.

Various patterns were observed and the evolutionists now reason that protein expression levels evolve under greater evolutionary constraint than gene transcription, via some unknown or unidentified mechanism.

Notice that evolutionary theory is completely superfluous to the story. The study made a scientific discovery, but it was then wrapped in an evolutionary narrative that does not help us to understand the new finding and adds nothing to the science. Furthermore, the evolution narrative, in spite of its uncertainty and vagueness, is presented as a fact. Evolutionists just aren’t that smart.

Here Come Those Mathematicians Again

A Gaping Gap?

The last time mathematicians informed evolutionists there was a problem, which was in 1966 at the Wistar Symposium, they were told that evolution is a fact so there must be something wrong with the math. Now Harvard’s Leslie Valiant is taking a different tack in his new book Probably Approximately Correct. Sounding like Stephen Wolfram, Valiant argues that nature works according to algorithms, and that includes evolution. According to Edward Frenkel’s New York Times book review, Valient proposes that ecorithms—algorithms that interact with their environment—are a key missing part of evolutionary theory:

The evolution of species, as Darwin taught us, relies on natural selection. But Dr. Valiant argues that if all the mutations that drive evolution were simply random and equally distributed, it would proceed at an impossibly slow and inefficient pace.

Darwin’s theory “has the gaping gap that it can make no quantitative predictions as far as the number of generations needed for the evolution of a behavior of a certain complexity,” he writes. “We need to explain how evolution is possible at all, how we got from no life, or from very simple life, to life as complex as we find it on earth today. This is the BIG question.”

Dr. Valiant proposes that natural selection is supplemented by ecorithms, which enable organisms to learn and adapt more efficiently. Not all mutations are realized with equal probability; those that are more beneficial are more likely to occur. In other words, evolution is accelerated by computation.

Well natural selection needs something. Why not ecorithms?

You Won’t Believe This New Epicycle: Congruence Incongruence is a Powerful Phylogenetic Signal

That's Creative

Remember how evolution was confirmed by congruence and proven by parsimony? The idea was that different anatomical comparisons lead to the same evolutionary tree. Even at the genetic level, different genes told the same evolutionary story. Similar evolution trees are derived from completely different genes. Such congruence of independent data was predicted by evolution and evolutionists have consistently proclaimed it as a powerful confirmation of the fact of evolution. It is, as evolutionists like to say, a powerful phylogenetic signal. There’s only one problem: all of this is false. It is yet another example of evolution’s theory-laden science where the findings are dictated not by the data but by the doctrine. There is no powerful phylogenetic signal. That is a myth. For when evolutionists construct their phylogenies, they first filter out the anatomical comparisons that don’t cooperate. But that is not enough so after their first try they filter some more. As one evolutionist admitted, “We are trying to figure out the phylogenetic relationships of 1.8 million species and can’t even sort out 20 [types of] yeast.” And so it is good to see a new paper that admits that data are routinely filtered in order to satisfy stringent criteria so as to eliminate the possibility of incongruence.

And what is the solution to this dilemma? As usual, a theoretical failure is converted into a success by adding yet more epicycles. Or as Lakatos might have put it, the core idea is protected by the addition of yet more auxiliary hypotheses. In this case, the incredible emerging view is that incongruence is now to be interpreted as a powerful phylogenetic signal that is desirable, as it often illuminates previously poorly understood evolutionary phenomena. Once again a prediction that was hailed as a powerful proof of evolution turns out to be false, and the story is simply flipped on its head, thus preserving the success of the theory. Where congruence was once claimed as a powerful phylogenetic signal, now incongruence takes its place as the powerful phylogenetic signal. You cannot make this stuff up.

What Origin of Life Research Really Tells Us

The Great Cover Up 

Here is an experiment you can try next time you clean out your refrigerator. When you excavate that old jar from way in the back of your refrigerator which long ago held something edible but is now covered with growths of various colors, scrape off some of that growth and put it into a pot of boiling water. After boiling for several minutes let the water cool off and then pour the water into a little pond that has no living organisms and mimics the conditions of the early Earth. Do you think that those organic chemicals from the refrigerator will eventually reassemble and produce new living cells? Evolutionists do. In fact it’s worse. Evolutionists believe life will spontaneously appear even without the benefit of adding that full complement of boiled over organic ingredients. In order to understand fully the extent to which evolution abuses science one must understand two things: what the science really says and what evolutionists really say.

There is no scientific demonstration that life spontaneously arises from non life. Furthermore, the science doesn’t even indicate that such a thing occurs, even if it hasn’t been actually demonstrated. In fact, after almost a century of research, what the science reveals is that there are significant problems with the idea.

A partisan assessment from an evolution opponent? Not at all. I would be delighted to discover that life can spring up spontaneously. How fascinating that would be. But that simply is not what science has told us, like it or not. There does not exist a single study or experiment even coming close to showing how this could happen. This is not a partisan assessment, it is simply a scientific fact. That is what the science really says.

Now for what evolutionists really say. What many people are unaware of is that evolutionists take a position completely contrary to the science. I do not mean that evolutionists are hoping to reverse the scientific findings. I mean they are contradicting the scientific findings. Evolutionists literally make bold, unequivocal claims that the spontaneous origin of life from non life is a known scientific fact.

It may seem astonishing to those unfamiliar with evolutionary thought. But this blatant lie is typical of how evolutionists misrepresent the science. For example, leading science writer Carl Zimmer wrote in his well-received book Evolution: The Triumph of an Idea that scientists “have found compelling evidence that life could have evolved into a DNA-based microbe in a series of steps.”

Writers such as Zimmer do not contrive such claims, they come from the evolution researchers. As no less than the National Academy of Science declared. “For those who are studying the origin of life, the question is no longer whether life could have originated by chemical processes involving nonbiological components. The question instead has become which of many pathways might have been followed to produce the first cells”? [1]

Recently this high confidence was again evident in a peer-reviewed paper by David Penny and coworkers which begins:

There are some areas of science where there is still strong resistance to basic scientific conclusions: anthropogenic climate change, the reality of long term evolution, the origin of life, and the safety and efficacy of vaccination programs are well-known examples.

It would be difficult to imagine a greater misrepresentation of science. To be sure evolution is not a good scientific theory, but the real abuse of science is in evolution’s misrepresentation of science.

1. National Academy of Sciences, Science and Creationism: A View from the National Academy of Sciences, 2d ed. (Washington, D.C.: National Academy Press, 1999) 6.

Failure: How Evolutionists React

A Case Study in Protein Evolution

Proteins are highly complex molecular machines that perform essential tasks in our bodies. They also are a good example of what is wrong with evolutionary theory. The first problem with evolutionary theory is that it is unlikely. Proteins are not the first or only problem for evolution. Problems with evolution have been known since 1859 and before. But proteins provide a better, more quantitative, look at the problem than is usually available from biological designs. The second problem goes deeper into evolutionary thinking, for proteins reveal how evolutionists respond when confronted with undeniable scientific problems.

There’s no question that the human brain would have been quite a challenge to evolve from random biological change. Random mutations are not likely to have constructed it. Not in millions of years, and not in billions of years. And natural selection doesn’t help because selection does not coax the right mutations to occur. Every random mutation is, well, random. It is independent of need.

But what are the odds of evolving a brain? The chances are so astronomically against evolution that computing them is difficult. Evolution has always enjoyed this uncertainty. Darwin did not propose an idea that was just slightly unlikely. He proposed an idea that was astronomically unlikely—far beyond human comprehension. All we could say is that evolution is not a good scientific theory.

Enter proteins. They consist of a string of molecules called amino acids. Evolutionists have estimated the number of attempts that evolution could possibly have to construct a new protein. Their upper limit is 10^43 (a one followed by 43 zeros) obtained by multiplying 10^30 (cells in the world) by 10^4 (new genes generated per cell per year) by 10^9 (years). The lower limit is 10^21 obtained by multiplying 10^9 (bacteria species in the world) by 10^3 (unique sequences per species) by 10^9 (years).

While these estimates are incredibly optimistic for several reasons, we’re going by the evolutionist’s numbers. And for typical proteins, even these optimistic estimates of the number of attempts fall short by more than 27 orders of magnitude. And these deficits are according to the evolutionist’s own estimates of how many attempts would be required to find a typical protein.

One study concluded that 10^63 attempts would be required for a relatively short protein. And a similar result (10^65 attempts required) was obtained by comparing protein sequences.

Another study found that 10^64 to 10^77 attempts are required, and another study concluded that 10^70 attempts would be required. So something like 10^70 attempts are required yet only 10^43 attempts are possible. Even with these unrealistically conservative numbers provided by studies done by evolutionists, there is a shortfall of 27 orders of magnitude. Of course the real shortfall is much greater.

The numbers don’t add up. Proteins reveal scientific problems for evolution. What is interesting is how evolutionists react to these problems.

One professor once told me that these sorts of “problems” don’t count because they come from evolutionists. This is a common response. If the protein results posed scientific problems, then why are those researchers still evolutionists? But evolution is not a theory that is allowed to be wrong. Evolutionists blackball, ostracize and reject anyone who doesn’t go along with their belief. Breaking rank carries a considerable cost.

Furthermore, when it is creationists or IDs who make such findings, they are criticized for having a religious bias. So evolution is fully protected. If an evolutionist presents problems for evolution, then the problems don’t count because the person is an evolutionist. If a non evolutionist presents problems for evolution, then the problems don’t count because the person is not an evolutionist.

Another response from evolutionists, and one often proposed by those evolutionists reporting on negative results, is that the problem will be solved by future research. Problems are always cast as “research problems” not as theory problems. And future research, one way or another, will solve the problem. Evolutionists understand what conclusions are allowed and not allowed.

It is of course true that future studies may solve the problem. I wouldn’t be surprised if potential avenues of protein evolution are discovered in the future (but that would present the even more profound problem of how matter and natural law just happened to be arranged so as to produce such unlikely molecular machines). On the other hand, I also wouldn’t be surprised if the results go in the opposite direction.

In fact, future research may reveal all kinds of things. Future research, for example, may continue to refute evolution. Who knows what future research will find. It is simply a misrepresentation of science to cast the results as consistent and supportive of evolution, with merely some details to be addressed by future research. This just isn't what science is telling us right now.

It is what it is. We know what science is telling us. We need to honestly acknowledge the science. Future findings may always reveal something different, but that may or may not happen. One can either acknowledge the facts of science, or live in denial.

Rare Codons Near the Beginning of a Gene Control Protein Expression Level

More Fine-Tuning

Various studies have shown that in order to produce a protein evolution would need roughly 10^70 attempts to get close enough for natural selection to take over. That is a 1 with 70 zeros after it. The number of attempts possible, on the other hand, is far less. One study concluded that 10^43 attempts may be possible. It is important to understand how tiny 10^43 is compared to 10^70. 10^43 is not about half of 10^70. It is not even close to half. In fact 10^43 is an astronomically tiny sliver of 10^70. Furthermore that study concluded that 10^43 attempts may be possible assumed, as a starting point, the existence of bacteria. In fact it assumed the Earth is covered with them. And bacteria, as every freshman knows, contain proteins. So in order to evolve a protein, evolutionists assume the prior existence of proteins, and still fail to resolve the problem. But we really haven’t even begun to address the problem.

Genes that code for proteins do not merely code for a string of amino acids that happens to perform some simple function. For beyond this, a gene codes for an incredible level of complexity. It has been discovered, for instance, that gene sequences are cleverly arranged to complement the cell’s error correction mechanisms and so minimize copying errors. On top of that information, the gene also contains signals that help to control the speed at which the new protein is synthesized. These signals have been found to be quite sophisticated.

Protein coding genes also influence how the protein synthesis process should work. Specifically, in addition to specifying the amino acids to be used in making the new protein, genes also include signals for which particular amino acid-bearing machine (the tRNA) should be used.

And once the new protein is synthesized, it must avoid the propensity of proteins to stick to each other and form fibrils in what is known as an amyloid. As one researcher explained, “The amyloid state is more like the default state of a protein, and in the absence of specific protective mechanisms, many of our proteins could fall into it.”

The problem is that short protein segments of say half a dozen amino acids can be self-complementary and sticky. If these sticky patches are on the exterior of a protein, then multiple copies of the protein can attach and form a growing and dangerous amyloid fibril.

Not surprisingly the cell has several mechanisms to protect against protein fibrillation. And beyond these protective mechanisms, the gene sequence itself arranges the protein’s amino acid sequence such that sticky patches are safely hidden away in the protein interior. This is a major threat to proteins and one evolutionist hypothesized, “Most proteins have evolved to fold in a way that effectively conceals their amyloid-prone segments.”

And there is yet more information the gene must carry. Not only must the protein not aggregate, but it may require transportation instructions that help it to be shuttled to the right place in the cell.

Also, some genes are overlapping with other genes. In other words, the stretch of DNA where a gene resides may be shared with another gene entirely. So the genetic information is now doubled. And even if this is not the case, researchers are increasingly finding that genes perform multiple tasks. In what is known as gene sharing, the protein product of a gene may carry out several separate and distinct functions. As one researcher concluded, “protein multifunctionality is more the rule than the exception.” In fact, “Perhaps all proteins perform many different functions by employing as many different mechanisms.”

Consider the p53 protein for example. It is a tumor suppressor, a gene regulator, and it plays a role in cell growth, death and DNA repair. In another example, a protein was discovered to undergo a dramatic structural and functional change. When a phosphate group is attached to the right place the protein switches from (i) helping to translate the RNA copy of a gene into a new protein to (ii) working on making the RNA copy of the gene.

So you can see that the job of evolving a protein consists of far more than merely finding a simple function, which itself is far beyond evolution’s capabilities, even according to the evolutionist’s own numbers.

Now new research reveals yet more information in the gene. It has been known for years that it is crucial that the mRNA copy of the gene is not too stable. Otherwise it cannot be used to synthesize the protein. So the gene, when transcribed by RNA polymerase, must not produce an mRNA transcript that folds up too tightly.

The new research shows that rare codons that appear early in a gene sequence influence the mRNA stability, and in so doing strongly influence that protein expression level. In other words, built into a gene sequence are instructions that can control how much of the corresponding protein to make.

One wonders how many more signals are buried in genetic sequences.

Dean Baquet on Journalism’s Challenges

Wow, Just Wow

Dean Baquet told an audience of eager undergraduates last night at Penn State that journalism faces some serious challenges. The managing editor of the New York Times is concerned that “the craft of witnessing and reporting on the truth will die” and that printing accurately is one of the most difficult aspects in journalism right now. Truth? Let’s lower our sights and begin with something a bit more mundane, such as journalistic bias and viewpoint discrimination, which his newspaper once again demonstrated this weekend when it castigated anyone who dares to question that the species spontaneously arose. The problem with such people is they question the science, “often getting down to very technical details.” Thankfully the New York Times has exposed this underhanded ploy.

The problem is that editors such as Baquet don’t even recognize journalistic bias in their own publications, much less do anything about it.

The Atlantic: Inherit the Wind One of the “Great Trial Movies of All Time”

Whig History

Now Andrew Cohen joins Judge John Jones in his approbation of the fictional play and movie, Inherit the Wind. In the hands of evolutionists the Lawrence and Lee script has codified the Warfare Thesis, a myth so useful that evolutionists continue to promote the movie at the cost of their own credibility. For students all of this provides a living example of the age-old anti-intellectual practice of remaking and retelling history to justify today’s lies and discrimination—the sort of thing that the script was originally, and ironically, meant to expose.

Cohen not only gives high praise to Inherit the Wind, absurdly calling it “one of the great trial movies of all time,” he also approvingly cites equally spurious renditions of on-going policy disputes from the New York Times and the Los Angeles Times, reviewed here, here and here.