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New Animation on Topoisomerase Demonstrates Irrationality of Denying Design Evidence in Biology

Brian Miller
Image: Topoisomerase II, by Discovery Institute.

Our recently released animation of a topoisomerase enzyme demonstrates evidence of design that cannot be honestly denied. Topoisomerases untangle DNA during replication and transcription, and they perform other essential functions in cells. The type I family breaks one strand of the DNA double helix, passes the second strand through the break, and then splices the first strand back together. The type II family breaks both strands of a segment of DNA, passes a second segment through the break, and then splices together the first segment. Each family includes several distinct subfamilies. The animation illustrates the operations of a type II enzyme.

Topoisomerase Structure and Dynamics

Replication or transcription of DNA stresses the macromolecule, resulting in supercoiling. Topoisomerase II relieves the stress by reducing the number of supercoils. The enzyme is composed of two identical halves that combine to form three gates that open and close in a precise order. It performs a series of steps that can best be described, based on the latest research (herehere), as follows:

  1. One DNA segment enters the upper gate and then binds to the middle gate. A second strand enters the top gate. The middle and lower gates are initially closed. 
  2. The middle gate cuts the first strand in two. Two ATP molecules attach to the upper gate, and the gate closes. 
  3. One of the ATP molecules breaks apart releasing energy that might help keep the upper gate together for the next steps. 
  4. The middle gate separates the two ends of the first DNA segment, creating a gap. Both DNA ends remain attached to the middle gate. 
  5. The second DNA segment moves through the gap. 
  6. The upper gate rotates. The middle gate closes, and the two DNA ends are reconnected.
  7. The enzyme breaks apart the remaining ATP molecule, and the lower gate opens, allowing the second DNA segment to leave. 
  8. The lower gate closes, and the upper gate opens, releasing the first DNA segment. 

After the last step, the topoisomerase is reset and ready to perform the same process again. 

The evidence of design in this molecular machine’s operations is self-evident. Every step is meticulously orchestrated to achieve the goal of untangling DNA, which is crucial for a cell’s survival. 

The Failure of Evolutionary Explanations

Attempts to explain the enzyme’s origin through natural processes are doomed to failure. Most of the steps are essential not only for the enzyme to achieve its goal of relaxing DNA, but they are required for it to not harm the cell. If the enzyme broke DNA segments without mending them, the cell would quickly die. The same holds true for capturing DNA without releasing it. And the enzyme must extract energy from ATP to drive the required structural changes and DNA manipulations. All these features must exist at once. Initial mutations moving an ancestral protein toward the topoisomerase goal would disadvantage a cell long before benefiting it, so they would quickly vanish from the population. 

Attempts to construct evolutionary scenarios are further challenged by the fact that several completely distinct types of enzymes reside in different taxa. One type only exists in a single species. Molecular biologists Patrick Forterre and Danièle Gadelle respond to this challenge in a manner that psychologists would label projection

Topoisomerases are essential enzymes that solve topological problems arising from the double-helical structure of DNA. As a consequence, one should have naively expected to find homologous topoisomerases in all cellular organisms, dating back to their last common ancestor. However, as observed for other enzymes working with DNA, this is not the case. Phylogenomics analyses indicate that different sets of topoisomerases were present in the most recent common ancestors of each of the three cellular domains of life…An intelligent designer would have probably invented only one ubiquitous Topo I and one ubiquitous Topo II to facilitate the task of future biochemists.

Their assessment of the implications for the employment of multiple topoisomerases is completely backwards. Intelligent agents often choose to implement very different solutions to the same problem to tailor each choice to its context. Automotive engineers design both internal combustion and electrical motors to achieve the same goal in manners that best fit the needs of different drivers. In contrast, the evolution of even one topoisomerase is implausible. The existence of multiple versions only exacerbates the problem. 

Implications for the Origin of Life

The greatest challenge is that a topoisomerase enzyme is required before a cell can reproduce. This conclusion follows from the fact that one is needed to even transcribe viral DNA segments, which are far smaller than the genomes of minimally complex cells. Consequently, materialist origin-of-life scenarios must account for the enzyme’s genesis by appealing only to physical and chemical processes that occurred on the early earth. 

More specifically, theorists must imagine something along the lines of the following (herehere):

  1. Cycles of hydration and dehydration initiated near a water source with a highly pure and concentrated mixture of multiple homochiral amino acids (i.e., only left-handed or right-handed versions of molecules exist). 
  2. The cycles progressed with miraculous precision to join the molecules together with the correct linkage to form a multitude of chains hundreds of amino acids long.
  3. Some chains formed with the correct sequences to fold into topoisomerase-like enzymes. 
  4. At least one of the enzymes migrated to a locale that served as the staging ground for a nascent cell. In practice, multiple copies of the enzyme would likely have been required to maintain transcription at a rate that could have maintained the cell. 
  5. The enzyme penetrated the cell membrane and then integrated with the DNA replication and transcription processes. 

Numerous Insurmountable Hurdles 

Each stage faces numerous insurmountable hurdles (hereherehere):

  1. All origin-of-life experiments primarily generate only trace amounts of a few amino acids. Those approaches that most accurately model the atmosphere on the early earth produce nothing of significance. The mixtures generated in even the most orchestrated experiments are never homochiral. And they always include countless other molecules that would have prevented the amino acids from forming into long chains through deleterious cross reactions. 
  2. Even those amino acids that form into chains often link together with the wrong chemical bonds preventing chains from folding into viable proteins. 
  3. The probability is beyond remote that two near-identical sequences corresponding to the two halves of a functional topoisomerase-like enzyme emerge in the same area. 
  4. Any functional protein that formed would have broken apart long before it found its way anywhere near a developing protocell.
  5. The uptake of proteins in cells requires energy-dependent highly orchestrated mechanisms

At some point, one must acknowledge that the denial of the evidence of design displayed in the topoisomerase enzyme and other molecular machines does not result from a rational examination of the evidence and logical inquiry. It is an ideological position founded on blind faith in the philosophy of scientific materialism.