Reasons to Believe

Pseudoenzymes Illustrate Science’s Philosophical Commitments

A few months ago, I had a serious accident while shooting a compound bow in my backyard. The arrow jammed in the guide, and in my attempt to free the arrow, I caused the bow string to derail. When that happened, the string struck my left eye with such force that it fractured my orbit in five places and damaged my retina. I am now legally blind in my left eye. Thankfully, I still have some peripheral vision, but I lost all the central vision in my injured eye. (To mothers everywhere: Yes, I wasn’t careful and I shot my eye out. I should have listened.)

Because of my injury, there is a blacked-out area in the center part of my field of vision which prevents me from focusing with my left eye. Sometimes, if something is on my left side, I can’t see it—even if it is in plain view.

Science’s Blind Spot

Over the years I have come to appreciate that, very often, the creation/intelligent design vs. evolution controversy has less to do with the evidence on hand and more with how each side sees the evidence. As a case in point, when examining the features of biochemical systems, most creationists and intelligent design proponents readily see evidence of a Creator’s handiwork. Yet adherents to the evolutionary paradigm don’t see evidence for design at all. Instead, they see flawed designs. Why? It is because they view biochemical systems as the result of an unguided evolutionary history. According to this view, evolution’s mechanisms have cobbled together biochemical systems by co-opting and repurposing existing systems to generate novel biochemical functions. As such, evolution produces kludge-job designs. Not the elegant, sophisticated systems expected if life stems from a Creator’s handiwork.

In part, the differing perspectives are shaped by philosophical commitments and the expectations that flow from them. To expound upon this point, the philosophical framework for contemporary science is methodological naturalism. Accordingly, scientific explanations for the universe and phenomena within the universe (such as the characteristics of biochemical systems) must have a mechanistic accounting—an explanation exclusively rooted in natural processes. Any explanation that appeals to the work of supernatural agency violates the tenets of methodological naturalism and is not even entertained as a possibility.

The consequences of methodological naturalism are far ranging for the creation/intelligent design vs. evolution controversy. The constraints of methodological naturalism exclude a priori any model that appeals to intelligent agency to explain, say, the design of biochemical systems. So although biochemical systems bear the appearance of design, the scientific community must explain the design as a product of evolutionary mechanisms. Why? It is because they have no other option. If biochemical systems didn’t evolve, then they must have been created. But the tenets of methodological naturalism forbid this explanation. Hence, biochemical systems must have evolved—by default.

If biochemical systems arise via evolutionary mechanisms, then they must be cobbled together. They must be poorly designed. Consequently, adherents of the evolutionary paradigm are conditioned to see biochemical systems as poorly designed—even if they aren’t—because of their commitment to methodological naturalism. Many can’t see the design that is in plain view for creationists and intelligent design adherents.

The recent discovery of pseudoenzymes helps illustrate this point.

Pseudoenzymes: Evidence for Evolution or Intelligent Design?

The existence of pseudoenzymes came to light about a decade ago when the human genome sequence was made available for researchers to study. It turns out that almost every enzyme family encoded by the human genome includes seemingly nonfunctioning members. (Enzymes are proteins that catalyze—or facilitate—chemical reactions in the cell.) Biochemists have dubbed these nonfunctioning enzymes pseudoenzymes. These proteins bear structural resemblances to other members of their enzyme families, yet they are unable to catalyze chemical reactions.

Because researchers have already detected pseudoenzymes within every known enzyme family, they expect that many more pseudoenzymes await discovery. In fact, analysis of thousands of genomes has identified pseudoenzymes throughout the biological realm. To put it another way, pseudoenzymes seem to be pervasive in biochemical systems.

Evolutionary biologists view pseudoenzymes as a by-product of life’s evolutionary history. Presumably, these noncatalytic enzymes arose when genes encoding their functional counterpart became duplicated. After this event, the duplicated genes experienced mutations that disabled the catalytic function of their protein products, generating pseudoenzymes.

For adherents of the evolutionary paradigm, the widespread occurrence of pseudoenzymes serves as a prima facie (based on first impression) challenge to intelligent design, and a compelling reason to think that biochemical systems are the product of an evolutionary history. In this framework, pseudoenzymes are vestiges of life’s evolutionary past—nonfunctional biochemical scars that impede cellular functions.

On the other hand, as a creationist and intelligent design proponent, I resist this conclusion. Why? I resist it because I have a different set of presuppositions than most in the scientific community. I believe that life arose through a Creators direct intervention and that science has the tool kit to detect evidence of intelligent agency at work. Because of my precommitments, I would posit yet-to-be-discovered functions for pseudoenzymes and a rationale for why these enzymes bear structural similarity to catalytic counterparts within their enzyme family.

And this is exactly what biochemists have discovered—pseudoenzymes are indeed functional, and there are good reasons for why these biomolecules resemble their catalytic analogs.

The Role of and Rationale for Pseudoenzymes

In a recent primer written for the open access journal BMC Biology, two biochemists surveyed recent work on pseudoenzymes, concluding that this newly recognized class of biomolecules plays a key role in cellular signaling pathways.1

The authors reflect on the role that the evolutionary paradigm played in delaying this insight. They state:

Because of the prejudice that focused attention on the catalytic functions of enzymes in signalling pathways, for a long time pseudoenzymes were considered to be dead—and therefore evolutionary remnants or bystanders in cell signalling networks. Contrary to this view, however, pseudoenzymes have now emerged as crucial players operating with an impressive diversity of mechanisms that we are only beginning to understand.2

In other words, the biases created by viewing pseudoenzymes as the by-product of evolutionary processes hindered biochemists from identifying and characterizing the functional importance of pseudoenzymes.

But this flawed perspective of viewing pseudoenyzmes as junk is changing. To date, biochemists have identified at least four functional roles for pseudoenzymes:

  1. They serve as protein anchors, locating cell signaling enzymes to appropriate locations within the cell.
  2. They function as scaffolds bringing enzymes of the same signaling pathway into proximity with one another, allowing the enzymes to efficiently work in conjunction with one another.
  3. They modulate the function of cell signaling proteins by binding to them, exerting an allosteric-type effect.
  4. They compete with “catalytic” cell signaling enzymes by binding the substrate without transforming it, regulating substrate transformation.

In part, the functional significance of pseudoenzymes justifies viewing these biomolecules as the work of a Creator. But if these biomolecules are designed, why would pseudoenzymes be so structurally like their catalytic cohorts? Evolutionary biologists maintain that these similarities reflect their evolutionary history. But if there is a reason for the structural similarities, it further justifies viewing pseudoenzymes as designed systems. As it turns out, a rationale does exist for the close similarity in structure between pseudoenzymes and other members of their enzyme family. As the authors of the survey note,

Enzyme structures are predisposed to mediating interactions with protein or metabolite ligands and thus these folds are the ideal templates for nature to repurpose for entirely new functions.3

In other words, for pseudoenzymes to influence cellular signaling pathways, they must bind substrates and interact with other proteins in the pathways with a high degree of specificity and with the identical specificity as their catalytic counterparts. Their close resemblance to their catalytic analogs allows these biomolecules to do just that.

In short, in fulfilling their vital role as regulators of cell signaling pathways, pseudoenzymes display elegance, sophistication, and ingenuity. As a creationist, this is the reason I view these systems as a Creator’s handiwork. Because the field of pseudoenzyme biochemistry is so young, I anticipate that the evidence for design will dramatically expand as we learn more about these surprising biomolecules.

Yet, despite everything we have learned about pseudoenzymes, adherents to the evolutionary paradigm simply can’t see these biomolecules as anything other than the product of an evolutionary history.

Because of the blind spot created by their philosophical commitments, the design of these systems is obscured from their view—and that causes them to miss the mark.



  1. Patrick Eyers and James Murphy, “The Evolving World of Pseudoenzymes: Proteins, Prejudice and Zombies,” BMC Biology 14 (November 2016): 98, doi:10.1186/s12915-016-0322-x.
  2. Ibid.
  3. Ibid.

Subjects: Biochemistry, Design