Today’s New Reason To Believe

Posted by Fazale ‘Fuz’ Rana, Ph.D.

DNA Optimized for Photostability, Adds to the Evidence for Design

About ten years ago my family and I moved from Ohio to sunny Southern California. I don’t think I could ever go back. I have no desire to experience ever again the frigid winters and humid summers that are major parts of living in the Midwest.

The year-round beautiful weather in the “southland” makes it possible to enjoy many carefree hours outdoors. But it also prompts some concerns about spending too much time in the sun. Soaking up too many of the Sun’s harmful rays can cause long-term damage to the skin—unless, of course, one lathers on the sunscreen.

Like Southern Californian sun “worshippers,” DNA also faces problems with short wavelength UV-radiation from the sun. This radiation can damage this all-important biomolecule. Fortunately, biochemists have discovered that DNA has unusual photostability. Scientists believe that specific structural features of DNA make it resistant to the harmful effects of the sun. It’s as if DNA has its own built-in sunscreen.

New research has uncovered some of the specific aspects of DNA structure that contribute to its unusual photostability, and—with this insight—add to the weight of evidence that biochemical systems are the work of a Creator.

The Structure of DNA

DNA consists of chain-like molecules known as polynucleotides. Two polynucleotide chains align in an antiparallel fashion to form a DNA molecule. (The two strands are arranged parallel to one another with the starting point of one strand in the polynucleotide duplex located next to the ending point of the other strand and vice versa.) The paired polynucleotide chains twist around each other to form the well-known DNA double helix. The cell’s machinery forms polynucleotide chains by linking together four different subunit molecules called nucleotides. The nucleotides used to build DNA chains are adenosine, guanosine, cytidine, and thymidine, famously abbreviated A, G, C, and T, respectively.

The nucleotide molecules that make up the strands of DNA are, in turn, complex molecules consisting of both a phosphate moiety, and a nucleobase (either adenine, guanine, cytosine, or thymine) joined to a 5-carbon sugar (deoxyribose).

Repeatedly linking the phosphate group of one nucleotide to the deoxyribose unit of another nucleotide forms the backbone of the DNA strand. The nucleobases extend as side chains from the backbone of the DNA molecule and serve as interaction points when the two DNA strands align and twist to form the double helix.

When the two DNA strands align, the adenosine (A) side chains of one strand always pair with thymidine (T) side chains from the other strand. Likewise, the guanosine (G) side chains from one DNA strand always pair with cytidine (C) side chains from the other strand.

The Photostability of DNA

As I pointed out in chapter seven of The Cell’s Design, biochemists have known for a while that the particular nucleobases found in DNA display ideal photophysical properties. Even though DNA routinely experiences photophysical damage, it could be far worse. It turns out that the optical properties of the bases found in nature minimize UV-induced damage. These nucleobases maximally absorb UV-radiation at the same wavelengths that are most effectively shielded by ozone. Moreover, the chemical structures of the nucleobases of DNA allow the UV-radiation to be efficiently radiated away after it has been absorbed, restricting the opportunity for damage.

To gain further insight into the structural features of DNA that contribute to its photostability, researchers from Germany prepared a number of model DNA compounds. It turns out that the molecular interactions that promote the pairing of the side groups in the DNA duplex help dissipate absorbed light energy. Variation of the nucleotide sequences in the strands of DNA also plays a role in photostability. This variability prevents long-lived excited states from forming when UV-radiation is absorbed by DNA.

It appears that DNA has been designed to have optimal photostability. This property is critical for DNA’s role in the cell as a data storage system. DNA harbors the information needed for the cell’s machinery to make proteins. It also houses the genetic information passed on to subsequent generations. If DNA isn’t stable, then the information it harbors will become distorted or lost. This will have disastrous consequences for the cell’s day-to-day operations and make long-term survival of life impossible.

As I discuss in The Cell’s Design, photostability is not the only feature of DNA that has been optimized. Other chemical and biochemical features appear to be carefully chosen to ensure its stability; again, a necessary property for a molecule that harbors the genetic information.

Optimized biochemical systems comprise evidence for biochemical intelligent design. Optimization of an engineered system doesn’t just happen—it results from engineers carefully optimizing their designs. It requires forethought, planning, and careful attention to detail. In the same way, the optimized features of DNA logically point to the work of a Divine engineer. It appears as if someone carefully designed the structure of DNA to spend many long hours in the sun.

Posted by Fazale ‘Fuz’ Rana, Ph.D.

New Insight into the Cell’s Quality-Control Systems Provided Added Evidence for Design

It’s easy to take garbage men for granted—until they go on strike or can’t do their job properly, which is the case in Naples, Italy.

Getting rid of trash is essential for well-run households, businesses, and communities. Piles of waste are an unpleasant health hazard.

Disposing of garbage is just as necessary for cells as it is for municipalities. Cells have to get rid of their molecular debris and waste to function properly. In most cases, the cell is able to remove its biomolecular rubbish. But in some cases, it can’t. The consequences can be devastating. Accumulating piles of biochemical waste are a health hazard for cells too. As a case in point, some neurodegenerative diseases, like Huntington’s, involve the build-up of biochemical waste in the form of protein aggregates.

Understandably, biologists are interested in trying to learn how and why protein waste accumulates in cells and what can be done to eliminate it. New work by Stanford University scientists published in Nature provides important insight into how protein waste is processed by the cell. This new knowledge suggests a possible strategy to help cells clear out intractable biomolecular garbage. This new understanding also adds to the evidence that life stems from a Creator’s hand.

Last week I described the make-up of the cell’s garbage and the central cogs in the cell’s waste-disposal machinery. This week I’ll describe the new research by the team of cell biologists from Stanford University and discuss its implications.

Protein Waste Disposal

Much of the cellular rubbish consists of protein aggregates. Proteins are chain-like molecules that fold into precise three-dimensional structures. A protein’s three-dimensional architecture determines its function. Proteins play a key role in virtually every cellular function and help form nearly every cellular structure.

Cells constantly make and destroy proteins. Specialized proteins used in particular activities are manufactured only when needed. Once these proteins have outlived their usefulness, the cell breaks them down into their constitutive amino acids. However, proteins that play a central role in the cell’s operation are produced on a continual basis. These proteins inevitably suffer damage from use and must be destroyed and replaced with newly made proteins. Faulty manufacturing also produces protein waste. The folding of newly made protein chains into their native three-dimensional architecture is error-prone. Misfolded proteins must be removed because they tend to form aggregates inside the cell.

Damaged or misfolded proteins are tagged with a small protein molecule called ubiquitin. These molecular tags inform the cell’s machinery that the damaged protein needs to be destroyed. A massive protein complex called a proteasome demolishes damaged, ubiquitinated proteins.

Accumulation of Protein Waste and Quality Control

Most unneeded, damaged, and misfolded proteins are readily cleared by the cell’s protein degradation system. However, some are not. These problematic proteins interact with each other to form large insoluble aggregates inside the cell. Most biologists think the failure of the cell’s machinery to eliminate these aggregated proteins stems from faulty quality-control operations in the cell.

As I describe in The Cell’s Design, every key stage, including the final step, of protein production is accompanied by quality-control checkpoints. These include the final step in the process. The proteasome eliminates any faulty proteins. The placement of these quality-assurance checkpoints occurs at strategic stages in the production process in a way that ensures reliable protein production while generating manufacturing efficiency.

In The Cell’s Design, I assert that biochemical quality assurance exemplifies the remarkable ingenuity that defines the cell’s chemistry and reinforces the conclusion that life has a supernatural basis. Effective and efficient quality-control procedures don’t just happen. Rather, they are characterized by intentional foresight. Sound quality-control systems require careful planning, a detailed understanding of the manufacturing process, the product, and the way that the product will be used. All of these features are evident in the quality-control activities in the cell.

Still, the inability to effectively eliminate aggregated proteins undermines the case for biochemical intelligent design if it is due to ineffective quality-control systems. But as new work reveals, the protein degradation process is much more complicated than previously thought.

Two Cellular Locales for Protein Waste Management

Stanford cell biologists performed a series of elegant experiments that revealed two cellular locales for protein waste disposal. The first region is situated near the juncture of the nucleus and the endoplasmic reticulum. This site is rich in proteasomes. Proteins sent to this location are highly ubiquinated and soluble. The proteasomes readily degrade or refold these proteins. (See my article from last week.)

The other site, which is located near the exterior of the cell, consists of insoluble protein deposits. Proteins sent to this location are lightly ubiquinated and insoluble. These proteins form insoluble aggregates that can’t be eliminated by the cell. Over time these deposits accumulate in the cell.

Proteins found in the second site include those associated with the onset of Huntington’s disease. They also includes proteins that would normally be cleared from the cell, but fail to be adequately ubiquinated because of stress. Under stressful conditions, a large number of proteins unfold, overwhelming the protein degradation system. The ageing process also contributes to proteins found in this site.

Production of insoluble protein deposits does not appear to be a malfunction of the cell’s quality-control systems. Instead it represents an elegant strategy for managing cellular waste. By piling insoluble protein aggregates into these deposits, the cell’s quality-control operations have effectively sequestered these harmful aggregates from the cell’s machinery, minimizing their harmful effects.

The authors of this study also note that the formation of these deposits provides a means to limit the transmission of insoluble protein aggregates to daughter cells generated from cell division. If distributed throughout the cell, a significant portion of the insoluble protein aggregates would be transferred to both daughter cells every time cell division took place. By incorporating all of the insoluble proteins into a single deposit, only one daughter cell is saddled with these potentially harmful materials. The other daughter cell winds up with a pristine cytoplasm.

Additionally, the Stanford researchers detected markers that flag the insoluble protein aggregates for autophagy). This process involves the breakdown of the cell’s own components by its digestive machinery. Autophagy provides a separate means to clear misfolded proteins from the cell independent from proteasomes.

Based on this new research, the formation of insoluble protein deposits no longer appears to be due to the failure of the cell’s quality-control systems. Instead it reveals that the quality assurance operations in the cell are far more complex and sophisticated than originally thought. The generation of insoluble protein aggregates serves a protective function for the cell and also provides a pathway to eliminate intractable protein conglomerations from inside the cell.

Like garbage in the streets of Naples, the biochemical evidence for intelligent design keeps piling up.

Fazale ‘Fuz’ Rana, Ph.D.

Rational Design of Novel Enzyme Highlights Biochemical Design

In 1978, three scientists (Hamilton Smith, Werner Arber, and Daniel Nathans) were awarded the Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes and their applications. These proteins make genetic engineering possible. They have also contributed to the wave of advances that led to the sequencing of the human genome and to the emergence of other biotechnologies.

Restriction enzymes (or endonucleases) are important for another reason. They represent an interesting example of a chicken-and-egg biochemical system and comprise part of the collection of evidence that indicates life must stem from a Creator. Recent work on these proteins highlights this point.

Endonucleases are a family of proteins. This class of biomolecules cleaves DNA. Restriction endonucleases cut both strands of DNA at specific nucleotide sequences, called restriction sites. Specifically, restriction endonucleases protect the cell from foreign DNA, like viruses, by cutting the invading DNA into fragments.

These vital biomolecules occur in conjunction with proteins (called DNA methylases) that attach methyl groups to the same DNA sequences that would normally be cleaved by restriction endonucleases. When these sequences are methylated, restriction endonucleases cannot cut them. Restriction sites of the bacterial DNA are methylated to completely protect the bacterial DNA from being chopped up by its own restriction endonulceases. Foreign DNA, however, is not afforded this same protection.

DNA methylases and restriction endonucleases form a chicken-and-egg pair. Restriction endonucleases would destroy bacterial DNA without DNA methylases. On the other hand, if bacteria did not utilize restriction endonucleases there would be no need for DNA methylases. These two proteins are interdependent and must come into existence simultaneously.

New research by scientists from the Indian Institute of Science (Bangalore, India) helps demonstrate why biochemical systems like restriction endonucleases require the work of an intelligent Agent. These researchers performed experiments to understand the origin of restriction endonucleases from an evolutionary perspective. They also wanted to develop a strategy for engineering novel, nonnatural restriction endonucleases.

Evolutionary biologists think restriction endonucleases evolved from non-specific endonucleases through point mutations in the gene region that codes the DNA binding site on the protein surface. According to this model, once specificity was established recombination and genetic shuffling of the DNA sequences that encode the DNA recognition sites would have generated new restriction endonucleases with different specificities.

To explore this possibility the research team attempted to engineer a highly specific restriction endonuclease from one (R. KpnI) that promiscuously binds to DNA. To accomplish this goal, the scientists employed a rational design strategy to determine which amino acids in the R. KpnI structure to change. These workers had to make use of the detailed understanding of this protein’s structure and functional properties in order to develop the redesign strategy.

They successfully achieved their intended goal by replacing an aspartic acid residue with an isoleucine moiety at amino acid position 163 in the R. KpnI protein chain.

This research illustrates how carefully-thought-through single amino acid substitutions can alter the specificity of restriction endonucleases. This is important work that paves the way to engineer novel, nonnatural restriction enzymes that can expand the arsenal of tools available to molecular biologists and biochemists.

The researchers involved in this study also interpreted their success as support for the evolutionary origin of restriction enzymes with point mutations ushering in the first stage in the molecular evolution of these proteins. At first glance, this interpretation seems warranted.

Still, it’s important to keep in mind that the production of the highly specific restriction endonuclease from the original promiscuous protein required intelligent input from a team of highly trained biochemists who relied on the past work of other highly accomplished scientists. In a sense, this study empirically demonstrates that protein “evolution” requires the work of an intelligent Agent.

It’s also important to note that the researchers didn’t design the companion methylase protein. This protein isn’t necessary for most biotechnology applications. But without the methylase cohort, the reengineered restriction endonuclease would wreck havoc in vivo, destroying DNA that comprises the bacterial genome.

It’s very unlikely that a restriction endonulcease and its partner methylase would simultaneously appear in an evolutionary scenario. These coordinated events would require that changes in the restriction endonuclease would take place at exactly the same time as corresponding changes in the methylase. The only way for coordinated changes like this to happen is under the auspices of an intelligent Agent.

As I point out in my new book The Cell’s Design, human engineers frequently encounter chicken-and-egg problems when designing systems and processes. Everyday experience teaches that chicken-and-egg systems can come to fruition only through intentional planning and implementation. Chicken-and-egg systems, therefore, serve as a potent indicator of intelligent design.

I describe several other examples of chicken-and-egg systems in The Cell’s Design.