No Joke: New Pseudogene Function Smiles on the Case for Creation

No Joke: New Pseudogene Function Smiles on the Case for Creation

Time to confess. I now consider myself an evolutionary creationist. I have no choice. The evidence for biological evolution is so overwhelming…

…Just kidding! April Fool’s!

I am still an old-earth creationist. Even though the evolutionary paradigm is the prevailing framework in biology, I am skeptical about facets of it. I am more convinced than ever that a creation model approach is the best way to view life’s origin, design, and history. It’s not to say that there isn’t evidence for common descent; there is. Still, even with this evidence, I prefer old-earth creationism for three reasons.

  • First, a creation model approach can readily accommodate the evidence for common descent within a design framework.
  • Second, the evolutionary paradigm struggles to adequately explain many of the key transitions in life’s history.
  • Third, the impression of design in biology is overwhelming—and it’s becoming more so every day.

And that is no joke.

Take the human genome as an example. When it comes to understanding its structure and function, we are in our infancy. As we grow in our knowledge and insight, it becomes increasingly apparent that the structural and functional features of the human genome (and the genomes of other organisms) display more elegance and sophistication than most life scientists could have ever imagined—at least, those operating within the evolutionary framework. On the other hand, the elegance and sophistication of genomes is expected for creationists and intelligent design advocates. To put it simply, the more we learn about the human genome, the more it appears to be the product of a Mind.

In fact, the advances in genomics over the last decade have forced life scientists to radically alter their views of genome biology. When the human genome was first sequenced in 2000, biologists considered most of the sequence elements to be nonfunctional, useless DNA. Now biologists recognize that virtually every class of these so-called junk DNA sequences serve key functional roles.

If most of the DNA sequence elements in the human genome were truly junk, then I’d agree that it makes sense to view them as evolutionary leftovers, especially because these junk DNA sequences appear in corresponding locations of the human and primate genomes. It is for these reasons that biologists have traditionally interpreted these shared sequences as the most convincing evidence for common descent.

However, now that we have learned that these sequences are functional, I think it is reasonable to regard them as the handiwork of a Creator, intentionally designed to contribute to the genome’s biology. In this framework, the shared DNA sequences in the human and primate genomes reflect common design, not common descent.

Still, many biologists reject the common design interpretation, while continuing to express confidence in the evolutionary model. Their certainty reflects a commitment to methodological naturalism, but there is another reason for their confidence. They argue that the human genome (and the genomes of other organisms) display other architectural and operational features that the evolutionary framework explains best—and, in their view, these features tip the scales toward the evolutionary interpretation.

Yet, researchers continue to make discoveries about junk DNA that counterbalance the evidence for common descent, including these structural and functional features. Recent insights into pseudogene biology nicely illustrate this trend.

Pseudogenes

Most life scientists view pseudogenes as the remnants of once-functional genes. Along these lines, biologists have identified three categories of pseudogenes (unitary, duplicated, and processed) and proposed three distinct mechanisms to explain the origin of each class. These mechanisms produce distinguishing features that allow investigators to identify certain DNA sequences as pseudogenes. However, a pre-commitment to the evolutionary paradigm can influence many biologists to declare too quickly that pseudogenes are nonfunctional based on their sequence characteristics.1

The Mechanisms of Pseudogene Formation. Image credit: Wikipedia.

As the old adage goes: theories guide, experiments decide. There is an accumulation of experimental data which indicates that pseudogenes from all three classes have utility.

A number of research teams have demonstrated that the cell’s machinery transcribes processed pseudogenes and, in turn, these transcripts are translated into proteins. Both duplicated and unitary pseudogenes are also transcribed. However, except for a few rare cases, these transcripts are not translated into proteins. Most of duplicated and unitary pseudogene transcripts serve a regulatory role, described by the competitive endogenous RNA hypothesis.

In other words, the experimental support for pseudogene function seemingly hinges on the transcription of these sequences. That leads to the question: What about pseudogene sequences located in genomes that aren’t transcribed? A number of pseudogenic sequences in genomes seemingly sit dormant. They aren’t transcribed and, presumably, have no utility whatsoever.

For many life scientists, this supports the evolutionary account for pseudogene origins, making it the preferred explanation over any model that posits the intentional design of pseudogene sequences. After all, why would a Creator introduce mutationally damaged genes that serve no function? Isn’t it better to explain the presence of functional processed pseudogenes as the result of neofunctionalization, whereby evolutionary mechanisms co-opt processed pseudogenes and use them as the raw material to evolve DNA sequence elements into new genes?

Or, perhaps, is it better to view the transcripts of regulatory unitary and duplicated pseudogenes as the functional remnants of the original genes whose transcripts played a role in regulatory networks with other RNA transcripts? Even though these pseudogenes no longer direct protein production, they can still take part in the regulatory networks comprised of RNA transcripts.

Are Untranscribed Pseudogenes Really Untranscribed?

Again, remember that support for the evolutionary interpretation of pseudogenes rests on the belief that some pseudogenes are not transcribed. What happens to this support if these DNA sequences are transcribed, meaning we simply haven’t detected or identified their transcripts experimentally?

As a case in point, in a piece for Nature Reviews, a team of collaborators from Australia argue that failure to detect pseudogene transcripts experimentally does not confirm the absence of a transcription.2 For example, the transcripts for a pseudogene transcribed at a low level may fall below the experimental detection limit. This particular pseudogene would appear inactive to researchers when, in fact, the opposite is the case. Additionally, pseudogene expression may be tissue-specific or may take place at certain points in the growth and development process. If the assay doesn’t take these possibilities into account, then failure to detect pseudogene transcripts could just mean that the experimental protocol is flawed.

The similarity of the DNA sequences of pseudogenes and their corresponding “sister” genes causes another complication. It can be hard to experimentally distinguish between a pseudogene and its “intact” sister gene. This limitation means that, in some instances, pseudogene transcripts may be misidentified as the transcripts of the “intact” gene. Again, this can lead researchers to conclude mistakenly that the pseudogene isn’t transcribed.

Are Untranscribed Pseudogenes Really Nonfunctional?

These very real experimental challenges notwithstanding, there are pseudogenes that indeed are not transcribed, but it would be wrong to conclude that they have no role in gene regulation. For example, a large team of international collaborators demonstrated that a pseudogene sequence contributes to the specific three-dimensional architecture of chromosomes. By doing so, this sequence exerts influence over gene expression, albeit indirectly.3

Another research team determined that a different pseudogene plays a role in maintaining chromosomal stability. In laboratory experiments, they discovered that deleting the DNA region that harbors this pseudogene increases chromosomal recombination events that result in the deletion of pieces of DNA. This deletion is catastrophic and leads to DiGeorge/velocardiofacial syndrome.4

To be clear, these two studies focused on single pseudogenes. We need to be careful about extrapolating the results to all untranscribed pseudogenes. Nevertheless, at minimum, these findings open up the possibility that other untranscribed pseudogene sequences function in the same way. If past history is anything to go by when it comes to junk DNA, these two discoveries are most likely harbingers of what is to come. Simply put, we continue to uncover unexpected function for pseudogenes (and other classes of junk DNA).

Common Design or Common Descent?

Not that long ago, shared nonfunctional, junk DNA sequences in the human and primate genomes were taken as prima facia evidence for our shared evolutionary history with the great apes. There was no way to genuinely respond to the challenge junk DNA posed to creation models, other than to express the belief that we would one day discover function for junk DNA sequences.

Subsequently, discoveries have fulfilled a key scientific prediction made by creationists and intelligent design proponents alike. These initial discoveries involved single, isolated pseudogenes. Later studies demonstrated that pseudogene function is pervasive, leading to new scientific ideas such as the competitive endogenous RNA hypothesis, that connect the sequence similarity of pseudogenes and “intact” genes to pseudogene function. Researchers are beginning to identify functional roles for untranscribed pseudogenes. I predict that it is only a matter of time before biologists concede that the utility of untranscribed pseudogenes is pervasive and commonplace.

The creation model interpretation of shared junk DNA sequences becomes stronger and stronger with each step forward, which leads me to ask, When are life scientists going to stop fooling around and give a creation model approach a seat at the biology table?

Resources

Endnotes
  1. Seth W. Cheetham, Geoffrey J. Faulkner, and Marcel E. Dinger, “Overcoming Challenges and Dogmas to Understand the Functions of Pseudogenes,” Nature Reviews Genetics 21 (December 17, 2019): 191–201, doi:10.1038/s41576-019-0196-1.
  2. Cheetham et al., 191–201.
  3. Peng Huang, et al., “Comparative Analysis of Three-Dimensional Chromosomal Architecture Identifies a Novel Fetal Hemoglobin Regulatory Element,” Genes and Development 31, no. 16 (August 15, 2017): 1704–13, doi: 10.1101/gad.303461.117.
  4. Laia Vergés et al., “An Exploratory Study of Predisposing Genetic Factors for DiGeorge/Velocardiofacial Syndrome,” Scientific Reports 7 (January 6, 2017): id. 40031, doi: 10.1038/srep40031.