Dual coding genes in the dock for design

Dual-Coding Genes "Nearly Impossible by Chance" -- How Would Francisco Ayala Respond.
Casey Luskin

We mortals are easily impressed by palindromes -- words or phrases that have the same spelling forwards and backwards. But try writing a sentence which has two different meanings: One meaning is gained when you start with one letter of the first word, and then an entirely different meaning is understood when you start reading with the second letter of the first word. Such a sentence would be most impressive, but what if such "sentences" existed in our DNA?

Leading evolutionary biologist Francisco Ayala recently wrote in Proceedings for the National Academy of Sciences (PNAS) that "Chance is an integral part of the evolutionary process." Ayala then explained why he thinks Darwinian evolution is right and ID is wrong: "Biological evolution differs from a painting or an artifact in that it is not the outcome of preconceived design. The design of organisms is not intelligent but imperfect and, at times, outright dysfunctional." ("Darwin's greatest discovery: Design without designer," PNAS, 104:8567--8573 (May 15, 2007), emphasis added.) This questionable standard and conclusion is Ayala's punchline against ID.

What, then, does Ayala think of organisms whose design is intelligent and highly functional? A recent article in Public Library of Science discussed how dual-coding genes -- genes which overlap and code for multiple proteins when read through different reading frames -- are "hallmarks of fascinating biology" and "nearly impossible by chance" to the extent that evolutionary biologists have held "skepticism surrounding" their very existence. Now it seems they do exist, and they don't quite match Ayala's vision of biology, where "[c]hance is an integral part" of the "design of organisms is "dysfunctional" and "not intelligent." As the article, "A First Look at ARFome: Dual-Coding Genes in Mammalian Genomes," states:

Coding of multiple proteins by overlapping reading frames is not a feature one would associate with eukaryotic genes. Indeed, codependency between codons of overlapping protein-coding regions imposes a unique set of evolutionary constraints, making it a costly arrangement. Yet in cases of tightly coexpressed interacting proteins, dual coding may be advantageous. Here we show that although dual coding is nearly impossible by chance, a number of human transcripts contain overlapping coding regions. Using newly developed statistical techniques, we identified 40 candidate genes with evolutionarily conserved overlapping coding regions. Because our approach is conservative, we expect mammals to possess more dual-coding genes. Our results emphasize that the skepticism surrounding eukaryotic dual coding is unwarranted: rather than being artifacts, overlapping reading frames are often hallmarks of fascinating biology.
(Wen-Yu Chung, Samir Wadhawan, Radek Szklarczyk, Sergei Kosakovsky Pond, Anton Nekrutenko, "A First Look at ARFome: Dual-Coding Genes in Mammalian Genomes," PLOS Computational Biology, Vol. 3(5) (May, 2007), emphasis added.)


Does this sound like a "dysfunctional" process that is "not intelligent" in its design?

Predarwinian tech for design.

Rotary Engine Technology in Living Cells
Evolution News & Views

Gone are the days when evolutionists asserted that life would never produce wheels or gears. It was impossible, they thought, for structures like that to arrive by natural selection, because too many coordinated mutations would be required. A wheel without an axle would provide no fitness advantage. One gear could achieve nothing without a matching gear. That was before we learned about the planthopper with its gear-driven jumping feet and the exquisite rotary engines of cells: the bacterial flagellum and the ATP synthase motor, on which all life depends.


Since ATP synthase earned its discoverers a Nobel Prize in 1997, it has remained an object of fascination. New imaging techniques have been steadily improving the focus on these miniature rotary motors that measure a mere 20 x 10 nanometers (billionths of a meter) yet spin at up to 42,000 rpm (see here), generating 3 ATP per revolution. As some years have passed since we discussed these motors in detail, readers may wish to pause to refresh their memories with our video about these amazing machines before learning about some new discoveries:





The Glue-bricator

Even at their tiny scale, molecular motors have to deal with laws of physics that might limit their efficiency. These laws include friction and thermodynamics. A new essential fatty acid, named cardiolipin, has been identified in the membrane right where protons enter to drive rotation in the Fo ring. Cambridge scientists describe it in the Proceedings of the National Academy of Sciences as a molecule that "binds selectively but transiently to conserved lysine residues in the rotor," appearing to function both as a stabilizer (glue) and a lubricant.

It interacts specifically, transiently, and repeatedly with the rotor of the machine, possibly lubricating its rotation or participating directly in the generation of rotation from the transmembrane proton motive force. [Emphasis added.]
The interactions are "highly specific" in location and timing, the authors say:

These highly specific but brief interactions with the rotating c-ring are consistent with functional roles for cardiolipin in stabilizing and lubricating the rotor, and, by interacting with the enzyme at the inlet and exit of the transmembrane proton channel, in participation in proton translocation through the membrane domain of the enzyme.
In a review article in PNAS, two researchers from Max Planck Institute find this remarkable about the already "remarkable proteins that regenerate the molecular fuel for cellular processes in all domains of life." The Cambridge team "found a remarkable interaction pattern" in the glue-lubricator molecule cardiolipin (CL).

The results of Duncan et al. have major implications for our understanding of Fo action. Efficient c-ring rotation demands minimal friction with the surrounding membrane. Tightly bound CL, with the long residence times reported for cytochrome c oxidase and cytochrome bc1, could be unfavorable. Such tight interactions should interfere particularly with the functionally required rotation of the c-ring past the a-subunit. A tightly bound lipid would lock the rotor in a manner similar to some inhibitors. However, selective binding of CL to the c-ring appears to be required for the function and assembly of ATP synthase. The results of Duncan et al. help resolve this paradox: CL binds selectively but, at the same time, intermittently. In complexes III and IV, CL appears to act as a bridging glue; by contrast, it acts here as a lubricant.
This interaction clearly requires careful fine-tuning. Too much glue function would make the motor seize up. Too much lubricant would impair the ability of proton motive force to drive the rotor. High-resolution images of this interaction are eagerly awaited, they say; "Looking forward, we can expect further exciting developments in the CL story." And that story goes beyond just this molecular machine. The Cambridge scientists "point the way for both experimentation and computation to explore one of the most fundamental questions of molecular membrane biology: protein-lipid interactions in ATP synthase and beyond."

Freeze Frame

Freezing the little motors for cryo-electron microscopy has revealed details previously unnoticed. Two Canadian researchers review what is known about ATP synthase and its cousins, the vacuolar ATPases (V-ATPase) we wrote about last year. Now that cryo-EM has reached 6.9 angstrom resolution, the authors, writing in Science Advances, remind us that mutations to V-ATPase can lead to serious disorders, including kidney malfunction, brittle bones, cancer, and even deafness. No wonder the genetic sequences that build these machines are "highly conserved" down to specific amino acids. Here are some tidbits from the review:

More than a third of an organism's genome is devoted to the construction of membrane-embedded proteins.

Some F-type ATP synthases can work in reverse, pumping protons instead of using them to make ATP. Some can also pump sodium ions.

In eukaryotes, vacuolar ATPases can adjust the pH (acidity) inside of organelles. In archaea and some bacteria, they can adjust the pH outside the cell.

Since 10 protons in the Fo domain lead to 3 ATP in the F1 domain, scientists think that intrinsic flexibility of most F-type ATP synthases appears necessary for efficient function.

The most difficult parts to image are two half-channels embedded in the membrane that deliver protons to the rotating c-ring. Specifically placed arginine and glutamate residues appear to be thermodynamically essential for transferring the protons into the c-ring carousel and making it turn.

In some eukaryotes, vacuolar ATPases can dissociate their two primary components, essentially deactivating some of them to regulate their activity.

Within yeast cells, different isoforms of the ATPases can be found. One particular 62-residue loop shows the least sequence conservation. "Although a lack of conservation often indicates a lack of functional importance, evolutionary covariance analysis shows that this sequence varies between different sequences for the a-subunit in a remarkably coordinated way," the authors say. "Consequently, the proximity of this loop to the cytoplasmic half-channel, its net charge, and its isoform-dependent sequence suggest a functional role that differs in different subcellular compartments."

"V-ATPases have many interacting partners in cells, a testament to their importance in cell physiology."

When J.B.S. Haldane argued in a 1949 debate that natural selection would not be expected to produce wheels or magnets, he basically proposed a test: finding such structures would falsify Darwinian evolution. But holding evolutionists to their rules is like trying to win at Calvinball; they can change the rules of the game as they play. In 2003, molecular biologist Robin Holliday pulled a fast one. Knowing about ATP synthase and the bacterial flagellum by that time, he imagined that wheels should be ubiquitous, not limited to a few forms. Wikipedia says that he argued that "the absence of biological wheels argues against creationist or intelligent design accounts of the diversity of life, because an intelligent creator -- free of the limitations imposed by evolution -- would be expected to deploy wheels wherever they would be of use." Uncommon Descent responded:

Wheels need roads. Roads require a lot of exhausting, expensive maintenance and must be defended/policed. The off-road vehicle is a late invention because in former times, its function was performed by life forms who didn't need roads, like horses and camels.
Which the designer of nature did invent.


Holliday used a religious argument. He (and Wikipedia) should stick to science. In our uniform experience, machines and rotary engines are products of intelligent causes. So when we find rotary engines in living things, the inference to the best explanation is that intelligence had a role in their origin. That inference is strengthened by their abrupt appearance, ubiquity, conservation, efficiency, irreducible complexity in both structure and interactions, and indispensable functionality. It also helps to see that they are manufactured from coded instructions. Let the evidence drive the conclusions.

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