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

By Fazale Rana – April 1, 2020

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.


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?


  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.

Reprinted with permission by the author

Original article at:

Does Evolutionary Bias Create Unhealthy Stereotypes about Pseudogenes?

By Fazale Rana – March 18, 2020

Truth be told, we all hold to certain stereotypes whether we want to admit it or not. Though unfair, more often than not, these stereotypes cause little real damage.

Yet, there are instances when stereotypes can be harmful—even deadly. As a case in point, researchers have shown that stereotyping disrupts the healthcare received by members of so-called disadvantaged groups, such as African Americans, Latinos, and the poor.1

Healthcare providers are frequently guilty of bias towards underprivileged people. Often, the stereotyping is unconscious and unintentional. Still, this bias compromises the medical care received by people in these ethnic and socioeconomic groups.

Underprivileged patients are also guilty of stereotyping. It is not uncommon for these patients to perceive themselves as the victims of prejudice, even when their healthcare providers are genuinely unbiased. As a result, these patients don’t trust healthcare workers and, consequently, withhold information that is vital for a proper diagnosis.

Fortunately, psychologists have developed best practices that can reduce stereotyping by both healthcare practitioners and patients. Hopefully, by implementing these practices, the impact of stereotyping on the quality of healthcare can be minimized over time.

Recently, a research team from Australia identified another form of stereotyping that holds the potential to negatively impact healthcare outcomes.2 In this case, the impact of this stereotyping isn’t limited to disadvantaged people; it affects all of us.

A Bias Against Pseudogenes

These researchers have uncovered a bias in the way life scientists view the human genome (and the genomes of other organisms). Too often they regard the human genome as a repository of useless, nonfunctional DNA that arises as a vestige of evolutionary history. Because of this view, life scientists and the biomedical research community eschew studying regions of the human genome they deem to be junk DNA. This posture is not unreasonable. It doesn’t make sense to invest precious scientific resources to study nonfunctional DNA.

Many life scientists are unaware of their bias. Unfortunately, this stereotyping hinders scientific advance by delaying discoveries that could be translated into the clinical setting. Quite often, supposed junk DNA has turned out to serve a vital purpose. Failure to recognize this function not only compromises our understanding of genome biology, but also hinders biomedical researchers from identifying defects in these genomic regions that contribute to genetic diseases and disorders.

As psychologists will point out, acknowledging bias is the first step to solving the problems that stereotyping causes. This is precisely what these researchers have done by publishing an article in Nature Review Genetics.3 The team focused on DNA sequence elements called pseudogenes. Traditionally, life scientists have viewed pseudogenes as the remnants of once functional genes. Biologists have identified three categories of pseudogenes: (1) unitary, (2) duplicated, and (3) processed.

Researchers categorize DNA sequences as pseudogenes based on structural features. Such features indicate to the investigators that these sequence elements were functional genes at one time in evolutionary history, but eventually lost function due to mutations or other biochemical processes, such as reverse transcription and DNA insertion. Once a DNA sequence is labeled a pseudogene, bias sets in and researchers just assume that it lacks function—not because it has been experimentally demonstrated to be nonfunctional, but because of the stereotyping that arises out of the evolutionary paradigm.

The authors of the piece acknowledge that “the annotation of genomics regions as pseudogenes constitutes an etymological signifier that an element has no function and is not a gene. As a result, pseudogene-annotated regions are largely excluded from functional screen and genomic analyses.”4 In other words, the “pseudogene” moniker biases researchers to such a degree that they ignore these sequence elements as they study genome structure and function without ever doing the hard, experimental work to determine whether it is actually nonfunctional.

This approach is clearly misguided and detracts from scientific discovery. As the authors admit, “However, with a growing number of instances of pseudogene-annotated regions later found to exhibit biological function, there is an emerging risk that these regions of the genome are prematurely dismissed as pseudogenic and therefore regarded as void of function.”5

Discovering Function Despite Bias

The harmful effects of this bias become evident as biomedical researchers unexpectedly stumble upon function for pseudogenes, time and time, again, not because of the evolutionary paradigm, but despite it. These authors point out that many processed pseudogenes are transcribed and, of those, many are translated to produce proteins. Many unitary and duplicated pseudogenes are also transcribed. Some are also translated into proteins, but a majority are not. Instead they play a role in gene regulation as described by the competitive endogenous RNA hypothesis.

Still, there are some pseudogenes that aren’t transcribed and, thus, could rightly be deemed nonfunctional. However, the researchers point out that the current experimental approaches for identifying transcribed regions are less than ideal. Many of these methods may fail to detect pseudogene transcripts. However, as the researchers point out, even if a pseudogene isn’t transcribed it still may serve a functional role (e.g., contributing to chromosome three-dimensional structure and stability).

This Nature article raises a number of questions and concerns for me as a biochemist:

  • How widespread is this bias?
  • If this type of stereotyping exists toward pseudogenes, does it exist for other classes of junk DNA?
  • How well do we really understand genome structure and function?
  • Do we have the wrong perspective on the genome, one that stultifies scientific advance?
  • Does this bias delay the understanding and alleviation of human health concerns?

Is the Evolutionary Paradigm the Wrong Framework to Study Genomes?

Based on this article, I think it is safe to conclude that we really don’t understand the molecular biology of genomes. We are living in the midst of a scientific revolution that is radically changing our view of genome structure and function. The architecture and operations of genomes appear to be far more elegant and sophisticated than anyone ever imagined—at least within the confines of the evolutionary paradigm.

This insight also leads me to question if the evolutionary paradigm is the proper framework for thinking about genome structure and function. From my perspective, treating biological systems as the Creator’s handiwork provides a superior approach to understanding the genome. A creation model approach promotes scientific advance, particularly when the rationale for the structure and function of a particular biological system is not apparent. This expectation forces researchers to keep an open mind and drives further study of seemingly nonfunctional, purposeless systems with the full anticipation that their functional roles will eventually be uncovered.

Over the last several years, I have raised concerns about the bias life scientists have harbored as they have worked to characterize the human genome (and genomes of other organisms). It is gratifying to me to see that there are life scientists who, though committed to the evolutionary paradigm, are beginning to recognize this bias as well.

The first step to addressing the problem of stereotyping—in any sector of society—is to acknowledge that it exists. Often, this step is the hardest one to take. The next step is to put in place structures to help overcome its harmful influence. Could it be that part of the solution to this instance of scientific stereotyping is to grant a creation model approach access to the scientific table?


Pseudogene Function

The Evolutionary Paradigm Hinders Scientific Advance

  1. For example, see Joshua Aronson et al., “Unhealthy Interactions: The Role of Stereotype Threat in Health Disparities,” American Journal of Public Health 103 (January 1, 2013): 50–56, doi:10.2105/AJPH.2012.300828.
  2. Seth W. Cheetham, Geoffrey J. Faulkner, and Marcel E. Dinger, “Overcoming Challenges and Dogmas to Understand the Functions of Pseudogenes,” Nature Reviews Genetics 21 (March 2020): 191–201, doi:10.1038/s41576-019-0196-1.
  3. Cheetham, Faulkner, and Dinger, 191–201.
  4. Cheetham, Faulkner, and Dinger, 191–201.
  5. Cheetham, Faulkner, and Dinger, 191–201.

Reprinted with permission by the author

Original article at:

Genome Code Builds the Case for Creation

By Fazale Rana – December 18, 2019

A few days ago, I was doing a bit of Christmas shopping for my grandkids and I happened across some really cool construction kits, designed to teach children engineering principles while encouraging imaginative play. For those of you who still have a kid or two on your Christmas list, here are some of the products that caught my eye:

These building block sets are a far cry from the simple Lego kits I played with as a kid.

As cool as these construction toys may be, they don’t come close to the sophisticated construction kit cells use to build the higher-order structures of chromosomes. This point is powerfully illustrated by the insights of Italian investigator Giorgio Bernardi. Over the course of the last several years, Bernardi’s research teams have uncovered design principles that account for chromosome structure, a set of rules that he refers to as the genome code.1

To appreciate these principles and their theological implications, a little background information is in order. (For those readers familiar with chromosome structure, skip ahead to The Genome Code.)


DNA and proteins interact to make chromosomes. Each chromosome consists of a single DNA molecule wrapped around a series of globular protein complexes. These complexes repeat to form a supramolecular structure resembling a string of beads. Biochemists refer to the “beads” as nucleosomes.


Figure 1: Nucleosome Structure. Image credit: Shutterstock

The chain of nucleosomes further coils to form a structure called a solenoid. In turn, the solenoid condenses to form higher-order structures that constitute the chromosome.


Figure 2: Chromosome Structure Image credit: Shutterstock

Between cell division events (called the interphase of the cell cycle), the chromosome exists in an extended diffuse form that is not readily detectable when viewed with a microscope. Just prior to and during cell division, the chromosome condenses to form its readily recognizable compact structures.

Biologists have discovered that there are two distinct regions—labeled euchromatin and heterochromatin for chromosomes in the diffuse state. Euchromatin is resistant to staining with dyes that help researchers view it with a microscope. On the other hand, heterochromatin stains readily. Biologists believe that heterochromatin is more tightly packed (and, hence, more readily stained) than euchromatin. They have also learned that heterochromatin associates with the nuclear envelope.


Figure 3: Structure of the Nucleus Showing the Distribution of Euchromatin and Heterochromatin. Image credit: Wikipedia

The Genome Code

Historically, biologists have viewed chromosomes as consisting of compositionally distinct units called isochores. In vertebrate genomes, five isochores exist (L1, L2, H1, H2, and H3). The isochores differ in the composition of guanine- and cytosine-containing deoxyribonucleotides (two of the four building blocks of DNA). The GC composition increases from L1 to H3. Gene density also increases, with the H3 isochore possessing the greatest number of genes. On the other hand, the size of DNA pieces of compositional homogeneity decreases from L1 to H3.

Bernardi and his collaborators have developed evidence that the isochores reflect a fundamental unit of chromosome organization. The H isochores correspond to GC-rich euchromatin (containing most of the genes) and the L isochores correspond to GC-poor heterochromatin (characterized by gene deserts).

Bernardi’s research teams have demonstrated that the two groups of isochores are characterized by different distributions of DNA sequence elements. GC-poor isochores contain a disproportionately high level of oligo A sequences while GC-rich isochores harbor a disproportionately high level of oligo G sequences. These two different types of DNA sequence elements form stiff structures that mold the overall three-dimensional architecture of chromosomes. For example, oligo A sequences introduce curvature to the DNA double helix. This topology allows the double helix to wrap around the protein core that forms nucleosomes. The oligo G sequence elements adopt a topology that weakens binding to the proteins that form the nucleosome core. As Bernardi points out, “There is a fundamental link between DNA structure and chromatin structure, the genomic code.”2

In other words, the genomic code refers to a set of DNA sequence elements that:

  1. Directly encodes and molds chromosome structure (while defining nucleosome binding),
  2. Is pervasive throughout the genome, and
  3. Overlaps the genetic code by constraining sequence composition and gene structure.

Because of the existence of the genomic code, variations in DNA sequence caused by mutations will alter the structure of chromosomes and lead to deleterious effects.

The bottomline: Most of the genomic sequence plays a role in establishing the higher-order structures necessary for chromosome formation.

Genomic Code Challenges the Junk DNA Concept

According to Bernardi, the discovery of the genomic code explains the high levels of noncoding DNA sequences in genomes. Many people view such sequences as vestiges of an evolutionary history. Because of the existence and importance of the genomic code, the vast proportion of noncoding DNA found in vertebrate genomes must be viewed as functionally vital. According to Bernardi:

Ohno, mostly focusing on pseudo-genes, proposed that non-coding DNA was “junk DNA.” Doolittle and Sapienza and Orgel and Crick suggested the idea of “selfish DNA,” mainly involving transposons visualized as molecular parasites rather than having an adaptive function for their hosts. In contrast, the ENCODE project claimed that the majority (~80%) of the genome participated “in at least one biochemical RNA-and/or chromatin-associated event in at least one cell type.”…At first sight, the pervasive involvement of isochores in the formation of chromatin domains and spatial compartments seems to leave little or no room for “junk” or “selfish” DNA.3

The ENCODE Project

Over the last decade or so, ENCODE Project scientists have been seeking to identify the functional DNA sequence elements in the human genome. The most important landmark for the project came in the fall of 2012 when the ENCODE Project reported phase II results. (Currently, ENCODE is in phase IV.) To the surprise of many, the project reported that around 80 percent of the human genome displays biochemical activity—hence, function—with many scientists anticipating that that percentage would increase as phases III and IV moved toward completion.

The ENCODE results have generated quite a bit of controversy, to say the least. Some researchers accept the ENCODE conclusions. Others vehemently argue that the conclusions fly in the face of the evolutionary paradigm and, therefore, can’t be valid. Of course, if the ENCODE Project conclusions are correct, then it becomes a boon for creationists and intelligent design advocates.

One of the most prominent complaints about the ENCODE conclusions relates to the way the consortium determined biochemical function. Critics argue that ENCODE scientists conflated biochemical activity with function. These critics assert that, at most, about ten percent of the human genome is truly functional, with the remainder of the activity reflecting biochemical noise and experimental artifacts.

However, as Bernardi points out, his work (independent of the ENCODE Project) affirms the project’s conclusions. In this case, the so-called junk DNA plays a critical role in molding the structures of chromosomes and must be considered functional.

Function for “Junk DNA”

Bernardi’s work is not the first to recognize pervasive function of noncoding DNA. Other researchers have identified other functional attributes of noncoding DNA. To date, researchers have identified at least five distinct functional roles that noncoding DNA plays in genomes.

  1. Helps in gene regulation
  2. Functions as a mutational buffer
  3. Forms a nucleoskeleton
  4. Serves as an attachment site for mitotic apparatus
  5. Dictates three-dimensional architecture of chromosomes

A New View of Genomes

These types of insights are forcing us to radically rethink our view of the human genome. It appears that genomes are incredibly complex, sophisticated biochemical systems and most of the genes serve useful and necessary functions.

We have come a long way from the early days of the human genome project. Just 15 years ago, many scientists estimated that around 95 percent of the human genome consists of junk. That acknowledgment seemingly provided compelling evidence that humans must be the product of an evolutionary history. Today, the evidence suggests that the more we learn about the structure and function of genomes, the more elegant and sophisticated they appear to be. It is quite possible that most of the human genome is functional.

For creationists and intelligent design proponents, this changing view of the human genome provides reasons to think that it is the handiwork of our Creator. A skeptic might wonder why a Creator would make genomes littered with so much junk. But if a vast proportion of genomes consists of functional sequences, then this challenge no longer carries weight and it becomes more and more reasonable to interpret genomes from within a creation model/intelligent design framework.

What a Christmas gift!


Junk DNA Regulates Gene Expression

Junk DNA Serves as a Mutational Buffer

Junk DNA Serves a Nucleoskeletal Role

Junk DNA Plays a Role in Cell Division

ENCODE Project

Studies that Affirm the ENCODE Results

  1. Giorgio Bernardi, “The Genomic Code: A Pervasive Encoding/Molding of Chromatin Structures and a Solution of the ‘Non-Coding DNA’ Mystery,” BioEssays 41, no. 12 (November 8, 2019), doi:10.1002/bies.201900106.
  2. Bernardi, “The Genomic Code.”
  3. Bernardi, “The Genomic Code.”

Reprinted with permission by the author

Original article at:

Mutations, Cancer, and the Case for a Creator

By Fazale Rana – December 11, 2019

Cancer. Perhaps no other word evokes more fear, anger, and hopelessness.

It goes without saying that cancer is an insidious disease. People who get cancer often die way too early. And even though a cancer diagnosis is no longer an immediate death sentence—thanks to biomedical advances—there are still many forms of cancer that are difficult to manage, let alone effectively treat.

Cancer also causes quite a bit of consternation for those of us who use insights from science to make a case for a Creator. From my vantage point, one of the most compelling reasons to think that a Creator exists and played a role in the origin and design of life is the elegant, sophisticated, and ingenious designs of biochemical systems. And yet, when I share this evidence with skeptics—and even seekers—I am often met with resistance in the form of the question: What about cancer?

Why Would God Create a World Where Cancer Is Possible?

In effect, this question typifies one of the most common—and significant—objections to the design argument. If a Creator is responsible for the designs found in biochemistry, then why are so many biochemical systems seemingly flawed, inelegant, and poorly designed?

The challenge cancer presents for the design argument carries an added punch. It’s one thing to cite inefficiency of protein synthesis or the error-prone nature of the rubisco enzyme, but it’s quite another to describe the suffering of a loved one who died from cancer. There’s an emotional weight to the objection. These deaths feel horribly unjust.

Couldn’t a Creator design biochemistry so that a disease as horrific as cancer would never be possible—particularly if this Creator is all-powerful, all-knowing, and all-good?

I think it’s possible to present a good answer to the challenge that cancer (and other so-called bad designs) poses for the design argument. Recent insights published by a research duo from Cambridge University in the UK help make the case.1

A Response to the Bad Designs in Biochemistry and Biology

Because the “bad designs” challenge is so significant (and so frequently expressed), I devoted an entire chapter in The Cell’s Design to addressing the apparent imperfections of biochemical systems. My goal in that chapter was to erect a framework that comprehensively addresses this pervasive problem for the design argument.

In the face of this challenge it is important to recognize that many so-called biochemical flaws are not genuine flaws at all. Instead, they arise as the consequences of trade-offs. In their cellular roles, many biochemical systems face two (or more) competing objectives. Effectively managing these opposing objectives means that it is impossible for every aspect of the system to perform at an optimal level. Some features must be carefully rendered suboptimal to ensure that the overall system performs robustly under a wide range of conditions.

Cancer falls into this category. It is not a consequence of flawed biochemical designs. Instead, cancer reflects a trade-off between DNA repair and cell survival.

DNA Damage and Cancer

The etiology (cause) of most cancers is complex. While about 10 percent of cancers have a hereditary basis, the vast proportion results from mutations to DNA caused by environmental factors.

Some of the damage to DNA stems from endogenous (internal) factors, such as water and oxygen in the cell. These materials cause hydrolysis and oxidative damage to DNA, respectively. Both types of damage can introduce mutations into this biomolecule. Exogenous chemicals (genotoxins) from the environment can also interact with DNA and cause damage leading to mutations. So does exposure to ultraviolet radiation and radioactivity from the environment.

Infectious agents such as viruses can also cause cancer. Again, these infectious agents cause genomic instability, which leads to DNA mutations.


Figure: Tumor Formation Process. Image credit: Shutterstock

In effect, DNA mutations are an inevitable consequence of the laws of nature, specifically the first and second laws of thermodynamics. These laws make possible the chemical structures and operations necessary for life to even exist. But, as a consequence, these same life-giving laws also undergird chemical and physical processes that damage DNA.

Fortunately, cells have the capacity to detect and repair damage to DNA. These DNA repair pathways are elaborate and sophisticated. They are the type of biochemical features that seem to support the case for a Creator. DNA repair pathways counteract the deleterious effects of DNA mutation by correcting the damage and preventing the onset of cancer.

Unfortunately, these DNA repair processes function incompletely. They fail to fully compensate for all of the damage that occurs to DNA. Consequently, over time, mutations accrue in DNA, leading to the onset of cancer. The inability of the cell’s machinery to repair all of the mutation-causing DNA damage and, ultimately, protect humans (and other animals) from cancer is precisely the thing that skeptics and seekers alike point to as evidence that counts against intelligent design.

Why would a Creator make a world where cancer is possible and then design cancer-preventing processes that are only partially effective?

Cancer: The Result of a Trade-Off

Even though mutations to DNA cause cancer, it is rare that a single mutation leads to the formation of a malignant cell type and, subsequently, tumor growth. Biomedical researchers have discovered that the onset of cancer involves a series of mutations to highly specific genes (dubbed cancer genes). The mutations that cause cells to transform into cancer cells are referred to as driver mutations. Researchers have also learned that most cells in the body harbor a vast number of mutations that have little or no biological consequence. These mutations are called passenger mutations. As it turns out, there are thousands of passenger mutations in a typical cancer cell and only about ten driver mutations to so-called cancer genes. Biomedical investigators have also learned that many normal cells harbor both passenger and driver mutations without ever transforming. (It appears that other factors unrelated to DNA mutation play a role in causing a cancer cell to undergo extensive clonal expansion, leading to the formation of a tumor.)

What this means is that mutations to DNA are quite extensive, even in normal, healthy cells. But this factor prompts the question: Why is the DNA repair process so lackluster?

The research duo from Cambridge University speculate that DNA repair is so costly to cells—making extensive use of energy and cell resources—that to maintain pristine genomes would compromise cell survival. These researchers conclude that “DNA quality control pathways are fully functional but naturally permissive of mutagenesis even in normal cells.”2 And, it seems as if the permissiveness of the DNA repair processes generally have little consequence given that a vast proportion of the human genome consists of noncoding DNA.

Biomedical researchers have uncovered another interesting feature about the DNA repair processes. The processes are “biased,” with repairs taking place preferentially on the DNA strand (of the double helix) that codes for proteins and, hence, is transcribed. In other words, when DNA repair takes place it occurs where it counts the most. This bias displays an elegant molecular logic and rationale, strengthening the case for design.

Given that driver mutations are not in and of themselves sufficient to lead to tumor formation, the researchers conclude that cancer prevention pathways are quite impressive in the human body. They conclude, “Considering that an adult human has ~30 trillion cells, and only one cell develops into a cancer, human cells are remarkably robust at preventing cancer.”3

So, what about cancer?

Though cancer ravages the lives of so many people, it is not because of poorly designed, substandard biochemical systems. Given that we live in a universe that conforms to the laws of thermodynamics, cancer is inevitable. Despite this inevitability, organisms are designed to effectively ward off cancer.

Ironically, as we gain a better understanding of the process of oncogenesis (the development of tumors), we are uncovering more—not less—evidence for the remarkably elegant and ingenious designs of biochemical systems.

The insights by the research team from Cambridge University provide us with a cautionary lesson. We are often quick to declare a biochemical (or biological) feature as poorly designed based on incomplete understanding of the system. Yet, inevitably, as we learn more about the system we discover an exquisite rationale for why things are the way they are. Such knowledge is consistent with the idea that these systems stem from a Creator’s handiwork.

Still, this recognition does little to dampen the fear and frustration associated with a cancer diagnosis and the pain and suffering experienced by those who battle cancer (and their loved ones who stand on the sidelines watching the fight take place). But, whether we are a skeptic or a believer, we all should be encouraged by the latest insights developed by the Cambridge researchers. The more we understand about the cause and progression of cancers, the closer we are to one day finding cures to a disease that takes so much from us.

We can also take added encouragement from the powerful scientific case for a Creator’s existence. The Old and New Testaments teach us that the Creator revealed by scientific discovery has suffered on our behalf and will suffer alongside us—in the person of Christ—as we walk through the difficult circumstances of life.


Examples of Biochemical Trade-Offs

Evidence that Nonfunctional DNA Serves as a Mutational Buffer

  1. Serena Nik-Zainal and Benjamin A. Hall, “Cellular Survival over Genomic Perfection,” Science 366, no. 6467 (November 15, 2019): 802–03, doi:10.1126/science.aax8046.
  2. Nik-Zainal and Hall, 802–03.
  3. Nik-Zainal and Hall, 802–03.

Reprinted with permission by the author

Original article at:

Satellite DNA: Critical Constituent of Chromosomes

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By Fazale Rana – June 26, 2019

Let me explain.

Recently, I wound up with a disassembled cabinet in the trunk of my car. Neither my wife Amy nor I could figure out where to put the cabinet in our home and we didn’t want to store it in the garage. The cabinet had all its pieces and was practically new. So, I offered it to a few people, but there were no takers. It seemed that nobody wanted to assemble the cabinet.

Getting Rid of the Junk

After driving around with the cabinet pieces in my trunk for a few days, I channeled my inner Marie Kondo. This cabinet wasn’t giving me any joy by taking up valuable space in the trunk. So, I made a quick detour on my way home from the office and donated the cabinet to a charity.

When I told Amy what I had done, she expressed surprise and a little disappointment. If she had known I was going to donate the cabinet, she would have kept it for its glass doors. In other words, if I hadn’t donated the cabinet, it would have eventually wound up in our garage because it has nice glass doors that Amy thinks she could have repurposed.

There is a point to this story: The cabinet was designed for a purpose and, at one time, it served a useful function. But once it was disassembled and put in the trunk of my car, nobody seemed to want it. Disassembling the cabinet transformed it into junk. And since my wife loves to repurpose things, she saw a use for it. She didn’t perceive the cabinet as junk at all.

The moral of my little story also applies to the genomes of eukaryotic organisms. Specifically, is it time that evolutionary scientists view some kinds of DNA not as junk, but rather as purposeful genetic elements?

Junk in the Genome

Many biologists hold the view that a vast proportion of the genomes of other eukaryotic organisms is junk, just like the disassembled cabinet I temporarily stored in my car. They believe that, like the unwanted cabinet, many of the different types of “junk” DNA in genomes originated from DNA sequences that at one time performed useful functions. But these functional DNA sequences became transformed (like the disassembled cabinet) into nonfunctional elements.

Evolutionary biologists consider the existence of “junk” DNA as one of the most potent pieces of evidence for biological evolution. According to this view, junk DNA results when undirected biochemical processes and random chemical and physical events transform a functional DNA segment into a useless molecular artifact. Junk pieces of DNA remain part of an organism’s genome, persisting from generation to generation as a vestige of evolutionary history.

Evolutionary biologists highlight the fact that, in many instances, identical (or nearly identical) segments of junk DNA appear in a wide range of related organisms. Frequently, the identical junk DNA segments reside in corresponding locations in these genomes—and for many biologists, this feature clearly indicates that these organisms shared a common ancestor. Accordingly, the junk DNA segment arose prior to the time that the organisms diverged from their shared evolutionary ancestor and then persisted in the divergent evolutionary lines.

One challenging question these scientists ask is, Why would a Creator purposely introduce nonfunctional, junk DNA at the exact location in the genomes of different, but seemingly related, organisms?

Satellite DNA

Satellite DNA, which consists of nucleotide sequences that repeat over and over again, is one class of junk DNA. This highly repetitive DNA occurs within the centromeres of chromosomes and also in the chromosomal regions adjacent to centromeres (referred to as pericentromeric regions).


Figure: Chromosome Structure. Image credit: Shutterstock

Biologists have long regarded satellite DNA as junk because it doesn’t encode any useful information. Satellite DNA sequences vary extensively from organism to organism. For evolutionary biologists, this variability is a sure sign that these DNA sequences can’t be functional. Because if they were, natural selection would have prevented the DNA sequences from changing. On top of that, molecular biologists think that satellite DNA’s highly repetitive nature leads to chromosomal instability, which can result in genetic disorders.

A second challenging question is, Why would a Creator intentionally introduce satellite DNA into the genomes of eukaryotic organisms?

What Was Thought to Be Junk Turns Out to Have Purpose

Recently, a team of biologists from the University of Michigan (UM) adopted a different stance regarding the satellite DNA found in pericentromeric regions of chromosomes. In the same way that my wife Amy saw a use for the cabinet doors, the researchers saw potential use for satellite DNA. According to Yukiko Yamashita, the UM research head, “We were not quite convinced by the idea that this is just genomic junk. If we don’t actively need it, and if not having it would give us an advantage, then evolution probably would have gotten rid of it. But that hasn’t happened.”1

With this mindset—refreshingly atypical for most biologists who view satellite DNA as junk—the UM research team designed a series of experiments to determine the function of pericentromeric satellite DNA.2 Typically, when molecular biologists seek to understand the functional role of a region of DNA, they either alter it or splice it out of the genome. But, because the pericentromeric DNA occupies such a large proportion of chromosomes, neither option was available to the research team. Instead, they made use of a protein found in the fruit fly Drosophila melanogaster, called D1. Previous studies demonstrated that this protein binds to satellite DNA.

The researchers disabled the gene that encodes D1 and discovered that fruit fly germ cells died. They observed that without the D1 protein, the germ cells formed micronuclei. These structures reflect chromosomal instability and they form when a chromosome or a chromosomal fragment becomes dislodged from the nucleus.

The team repeated the study, but this time they used a mouse model system. The mouse genome encodes a protein called HMGA1 that is homologous to the D1 protein in fruit flies. When they damaged the gene encoding HMGA1, the mouse cells also died, forming micronuclei.

As it turns out, both D1 and HMGA1 play a crucial role, ensuring that chromosomes remain bundled in the nucleus. These proteins accomplish this feat by binding to the pericentromeric satellite DNA. Both proteins have multiple binding sites and, therefore, can simultaneously bind to several chromosomes at once. The multiple binding interactions collect chromosomes into a bundle to form an association site called a chromocenter.

The researchers aren’t quite sure how chromocenter formation prevents micronuclei formation, but they speculate that these structures must somehow stabilize the nucleus and the chromosomes housed in its interior. They believe that this functional role is universal among eukaryotic organisms because they observed the same effects in fruit flies and mice.

This study teaches us two additional lessons. One, so-called junk DNA may serve a structural role in the cell. Most molecular biologists are quick to overlook this possibility because they are hyper-focused on the informational role (encoding the instructions to make proteins) DNA plays.

Two, just because regions of the genome readily mutate without consequences doesn’t mean these sequences aren’t serving some kind of functional role. In the case of pericentromeric satellite DNA, the sequences vary from organism to organism. Most molecular biologists assume that because the sequences vary, they must not be functionally important. For if they were, natural selection would have prevented them from changing. But this study demonstrates that DNA sequences can vary—particularly if DNA is playing a structural role—as long as they don’t compromise DNA’s structural utility. In the case of pericentromeric DNA, apparently the nucleotide sequence can vary quite a bit without compromising its capacity to bind chromocenter-forming proteins (such as D1 and HMGA1).

Is the Evolutionary Paradigm the Wrong Framework to Study Genomes?

Scientists who view biology through the lens of the evolutionary paradigm are often quick to conclude that the genomes of organisms reflect the outworking of evolutionary history. Their perspective causes them to see the features of genomes, such as satellite DNA, as little more than the remnants of an unguided evolutionary process. Within this framework, there is no reason to think that any particular DNA sequence element harbors function. In fact, many life scientists regard these “evolutionary vestiges” as junk DNA. This clearly was the case for satellite DNA.

Yet, a growing body of data indicates that virtually every category of so-called junk DNA displays function. In fact, based on the available data, a strong case can be made that most sequence elements in genomes possess functional utility. Based on these insights, and the fact that pericentromeric satellite DNA persists in eukaryotic genomes, the team of researchers assumed that it must be functional. It’s a clear departure from the way most biologists think about genomes.

Based on this study (and others like it), I think it is safe to conclude that we really don’t understand the molecular biology of genomes.

It seems to me that we live in the midst of a revolution in our understanding of genome structure and function. Instead of being a wasteland of evolutionary debris, the architecture and operations of genomes appear to be far more elegant and sophisticated than anyone ever imagined—at least within the confines of the evolutionary paradigm.

This insight also leads me to wonder if we have been using the wrong paradigm all along to think about genome structure and function. I contend that viewing biological systems as the Creator’s handiwork provides a superior framework for promoting scientific advance, particularly when the rationale for the structure and function of a particular biological system is not apparent. Also, in addressing the two challenging questions, if biological systems have been created, then there must be good reasons why these systems are structured and function the way they do. And this expectation drives further study of seemingly nonfunctional, purposeless systems with the full anticipation that their functional roles will eventually be uncovered.

Though committed to an evolutionary interpretation of biology, the UM researchers were rewarded with success when they broke ranks with most evolutionary biologists and assumed junk regions of the genome were functional. Their stance illustrates the power of a creation model approach to biology.

Sadly, most evolutionary biologists are like me when it comes to old furniture. We lack vision and are quick to see it as junk, when in fact a treasure lies in front of us. And, if we let it, this treasure will bring us joy.


  1. University of Michigan, “Scientists Discover a Role for ‘Junk’ DNA,” ScienceDaily (April 11, 2018),
  2. Madhav Jagannathan, Ryan Cummings, and Yukiko M. Yamashita, “A Conserved Function for Pericentromeric Satellite DNA,” eLife 7 (March 26, 2018): e34122, doi:10.7554/eLife.34122.

Reprinted with permission by the author

Original article at:

Competitive Endogenous RNA Hypothesis Supports the Case for Creation

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When Francis Crick, codiscoverer of the DNA double helix, first conceived of molecular biology’s organizing principle in 1958, he dubbed it the central dogma. He soon came to regret the term. In his autobiographical account, What Mad Pursuit, Crick writes:

I called this idea the central dogma, for two reasons, I suspect. I had already used the obvious word hypothesis in the sequence hypothesis, and in addition I wanted to suggest that this new assumption was more central and more powerful….As it turned out, the use of the word dogma caused almost more trouble than it was worth. Many years later Jacques Monod pointed out to me that I did not appear to understand the correct use of the word dogma, which is a belief that cannot be doubted. I did apprehend this in a vague sort of way but since I thought that all religious beliefs were without foundation, I used the word the way I myself thought about it, not as most of the world does, and simply applied it to a grand hypothesis that, however plausible, had little direct experimental support.1

Even though Crick rued labeling his idea as “dogma,” the term seems to fit, all the connotations aside, because of its singular importance to molecular biology.

The Central Dogma of Molecular Biology

The central dogma of molecular biology describes the directional flow of information in the cell, which moves from DNA to RNA to proteins. Information can flow from DNA to DNA during DNA replication, from DNA to RNA during transcription, and from RNA back to DNA during reverse transcription. However, biochemical information can’t flow from proteins to either RNA or DNA.


Figure 1: The Central Dogma of Molecular Biology. Image credit: Shutterstock

Is There a New Dogma in Molecular Biology?

In my opinion as a biochemist, if there is an idea that has the potential to rival the significance of the central dogma, it just might be the competitive endogenous RNA (ceRNA) hypothesis. This newer model provides a comprehensive description of the role messenger RNA (mRNA) molecules play in regulating gene expression, thereby influencing the flow of information from DNA to proteins.

The ceRNA hypothesis also provides an elegant rationale for why the genomes of eukaryotic organisms contain pseudogenes (including unitary pseudogenes) and encode long noncoding RNA molecules. Additionally, it explains why duplicated pseudogenes resemble corresponding intact genes. In doing all this, the ceRNA hypothesis provides support for the RTB’s genomics model—which interprets the structure and activities associated with genomes from a creation or design standpoint. (An overview of the RTB genomics model can be found in the updated and expanded 2nd edition of Who Was Adam?)

The Competitive Endogenous RNA Hypothesis

I discuss the ceRNA hypothesis in a previous article. So, I’ll offer just a brief description here. According to the central dogma, the final step in the flow of biochemical information is the production of proteins at the ribosome, directed by the information housed in mRNA. Biochemists have discovered an elaborate mechanism that selectively degrades mRNA transcripts before they can reach this point. This degradation process controls gene expression by dictating the amount of protein produced.

Molecules called microRNAs bind to the mRNA’s 3′ untranslated region, which flags the transcript for destruction by RNA-induced silencing complex (RISC). A number of distinct microRNA species exist in the cell. Each microRNA species bind to specific sites in the 3′ untranslated region of mRNA transcripts. (These binding locations are called microRNA response elements or MREs.)

A network of genes shares the same set of MREs and, consequently, will bind to the same set of microRNAs. When one gene is transcribed, it will influence the expression of all the other genes in its network. And when one gene in the network becomes up-regulated (leading to increased transcription of that gene), the expression of all the genes in the network increases. Why? Because the increased level of that particular transcript exerts a “sponge effect” that consumes more of the microRNAs that would otherwise target other transcripts for degradation.

The Competitive Endogenous RNA Hypothesis and the Role of Junk DNA

The ceRNA hypothesis elegantly explains the functional utility of three classes of junk DNA: duplicated and unitary pseudogenes, plus long noncoding RNAs. As it turns out, the transcripts produced from these types of so-called junk DNA also harbor MREs. None of these transcripts codes for proteins yet they play an indispensable role in regulating gene expression. In fact, all three are much better suited for the role of molecular sponges precisely because they aren’t translated into proteins.

Of particular utility are duplicated pseudogenes due to their close structural resemblance to the corresponding coding genes. Duplicated pseudogenes not only exert a sponge effect but also serve as decoys that allow the transcripts of the intact genes to escape degradation and to be translated into proteins.

Is the Competitive Endogenous RNA Hypothesis Valid?

This question has generated a minor scientific controversy. Some studies provide experimental support for this idea while others question the physiological relevance of ceRNAs. In light of this debate, a team of researchers headed by investigators from Columbia University sought to validate this hypothesis on a large-scale.They discovered that ceRNA interactions can disrupt the expression of thousands of genes. The team concluded that “ceRNA regulation is the norm not the exception…and that ceRNA interactions have genome-wide effects on gene expression.”3

These researchers think that this insight sheds light on tumor biology because dysregulation of ceRNAs have been implicated in some cancers. Their work also has theological significance because it undermines one of the most significant challenges to design arguments and, in turn, can be marshaled in support of the RTB genomics model.

The Competitive Endogenous Hypothesis and the Case for a Creator

Evolutionary biologists have long maintained that identical (or nearly identical) junk DNA sequences (such as pseudogene sequences) found in corresponding locations in genomes of organisms that naturally cluster together (such as humans and the great apes) provide compelling evidence that these organisms must have evolved from a shared ancestor. This interpretation was compelling because junk DNA sequences seemed to be useless vestiges of evolutionary history.

Creationists and intelligent design proponents had little to offer by way of evidence for the intentional design of genomes. But research in recent years has revealed that virtually every class of junk DNA has function. It seems, then, that shared junk DNA sequences can be understood as shared designs, which is what the RTB genomics model predicts.

Additionally, the ceRNA hypothesis supports the RTB genomics even further. This hypothesis provides an elegant explanation for the widespread existence of pseudogenes in genomes and their structural similarity to intact genes.

Could it be that the idea of religious dogma affirming a Creator’s role in life’s design and history has merit?


  1. Francis Crick, What Mad Pursuit (New York: Basic Books, 1988), 109.
  2. Hua-Sheng Chiu et al., “High-Throughput Validation of ceRNA Regulatory Networks,” BMC Genomics 18 (2017): 418, doi:10.1186/s12864-017-3790-7.
  3. Chiu et al., 418.

Reprinted with permission by the author
Original article at:

Pseudogene Discovery Pains Evolutionary Paradigm

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It was one of the most painful experiences I ever had. A few years ago, I had two back-to-back bouts of kidney stones. I remember it as if it were yesterday. Man, did it hurt when I passed the stones! All I wanted was for the emergency room nurse to keep the Demerol coming.


Figure 1: Schematic Depiction of Kidney Stones Moving through the Urinary Tract. Image Credit: Shutterstock

When all that misery was going down, I wished I was one of those rare individuals who doesn’t experience pain. There are some people who, due to genetic mutations, live pain-free lives. This condition is called hypoalgesia. (Of course, there is a serious downside to hypoalgesia. Pain lets us know when our body is hurt or sick. Because hypoalgesics can’t experience pain, they are prone to serious injury, etc.)

Biomedical researchers possess a keen interest in studying people with hypoalgesia. Identifying the mutations responsible for this genetic condition helps investigators understand the physiological processes that undergird the pain sensation. This insight then becomes indispensable to guiding efforts to develop new drugs and techniques to treat pain.

By studying the genetic profile of a 66-year-old woman who lived a lifetime with pain-free injuries, a research team from the UK recently discovered a novel genetic mutation that causes hypoalgesia.1 The mutation responsible for this patient’s hypoalgesia occurred in a pseudogene, a region of the genome considered nonfunctional “junk DNA.”

This discovery adds to the mounting evidence that shows junk DNA is functional. At this point, molecular geneticists have demonstrated that virtually every class of junk DNA has function. This notion undermines the best evidence for common descent and, hence, undermines an evolutionary interpretation of biology. More importantly, the discovery adds support for the competitive endogenous RNA hypothesis, which can be marshaled to support RTB’s genomics model. It is becoming more and more evident to me that genome structure and function reflect the handiwork of a Creator.

The Role of a Pseudogene in Mediating Hypoalgesia

To identify the genetic mutation responsible for the 66-year-old’s hypoalgesia, the research team scanned her DNA along with samples taken from her mother and two children. The team discovered two genetic changes: (1) mutations to the FAAH gene that reduced its expression, and (2) deletion of part of the FAAH pseudogene.

The FAAH gene encodes for a protein called fatty acid amide hydrolase (FAAH). This protein breaks down fatty acid amides. Some of these compounds interact with cannabinoid receptors. These receptors are located in the membranes of cells found in tissues throughout the body. They mediate pain sensation, among other things. When fatty acid amide concentrations become elevated in the circulatory system, it produces an analgesic effect.

Researchers found elevated fatty acid amide levels in the patient’s blood, consistent with reduced expression of the FAAH gene. It appears that both mutations are required for the complete hypoalgesia observed in the patient. The patient’s mother, daughter, and son all display only partial hypoalgesia. The mother and daughter have the same mutation in the FAAH gene but an intact FAAH pseudogene. The patient’s son is missing the FAAH pseudogene, but has a “normal” FAAH gene.

Based on the data, it looks like proper expression levels of the FAAH gene require an intact FAAH pseudogene. This is not the first time that biomedical researchers have observed the same effect. There are a number of gene-pseudogene pairs in which both must be intact and transcribed for the gene to be expressed properly. In 2011, researchers from Harvard University proposed that the competitive endogenous RNA hypothesis explains why transcribed pseudogenes are so important for gene expression.2

The Competitive Endogenous RNA Hypothesis

Biochemists and molecular biologists have long believed that the primary mechanism for regulating gene expression centered around controlling the frequency and amount of mRNA produced during transcription. For housekeeping genes, mRNA is produced continually, while for genes that specify situational proteins, it is produced as needed. Greater amounts of mRNA are produced for genes expressed at high levels and limited amounts for genes expressed at low levels.

Researchers long thought that once the mRNA was produced it would be translated into proteins, but recent discoveries indicate this is not the case. Instead, an elaborate mechanism exists that selectively degrades mRNA transcripts before they can be used to direct the protein production at the ribosome. This mechanism dictates the amount of protein produced by permitting or preventing mRNA from being translated. The selective degradation of mRNA also plays a role in gene expression, functioning in a complementary manner to the transcriptional control of gene expression.

Another class of RNA molecules, called microRNAs, mediates the selective degradation of mRNA. In the early 2000s, biochemists recognized that by binding to mRNA (in the 3′ untranslated region of the transcript), microRNAs play a crucial role in gene regulation. Through binding, microRNAs flag the mRNA for destruction by RNA-induced silencing complex (RISC).


Figure 2: Schematic of the RNA-Induced Silencing Mechanism. Image Credit: Wikipedia

Various distinct microRNA species in the cell bind to specific sites in the 3′ untranslated region of mRNA transcripts. (These binding locations are called microRNA response elements.) The selective binding by the population of microRNAs explains the role that duplicated pseudogenes play in regulating gene expression.

The sequence similarity between the duplicated pseudogene and the corresponding “intact” gene means that the same microRNAs will bind to both mRNA transcripts. (It is interesting to note that most duplicated pseudogenes are transcribed.) When microRNAs bind to the transcript of the duplicated pseudogene, it allows the transcript of the “intact” gene to escape degradation. In other words, the transcript of the duplicated pseudogene is a decoy. The mRNA transcript can then be translated and, hence, the “intact” gene expressed.

It is not just “intact” and duplicated pseudogenes that harbor the same microRNA response elements. Other genes share the same set of microRNA response elements in the 3′ untranslated region of the transcripts and, consequently, will bind the same set of microRNAs. These genes form a network that, when transcribed, will influence the expression of all genes in the network. This relationship means that all the mRNA transcripts in the network can function as decoys. This recognition accounts for the functional utility of unitary pseudogenes.

One important consequence of this hypothesis is that mRNA has dual functions inside the cell. First, it encodes information needed to make proteins. Second, it helps regulate the expression of other transcripts that are part of its network.

Junk DNA and the Case for Creation

Evolutionary biologists have long maintained that identical (or nearly identical) pseudogene sequences found in corresponding locations in genomes of organisms that naturally group together (such as humans and the great apes) provide compelling evidence for shared ancestry. This interpretation was persuasive because molecular geneticists regarded pseudogenes as nonfunctional, junk DNA. Presumably, random biochemical events transformed functional DNA sequences (genes) into nonfunctional garbage.

Creationists and intelligent design proponents had little to offer by way of evidence for the intentional design of genomes. But all this changed with the discovery that virtually every class of junk DNA has function, including all three types of pseudogenes (processed, duplicated, and unitary).

If junk DNA is functional, then the sequences previously thought to show common descent could be understood as shared designs. The competitive endogenous RNA hypothesis supports this interpretation. This model provides an elegant rationale for the structural similarity between gene-pseudogene pairs and also makes sense of the widespread presence of unitary pseudogenes in genomes.

Of course, this insight also supports the RTB genomics model. And that sure feels good to me.


  1. Abdella M. Habib et al., “Microdeletion in a FAAH Pseudogene Identified in a Patient with High Anandamide Concentrations and Pain Insensitivity,” British Journal of Anaesthesia, advanced access publication, doi:10.1016/j.bja.2019.02.019.
  2. Ana C. Marques, Jennifer Tan, and Chris P. Ponting, “Wrangling for microRNAs Provokes Much Crosstalk,” Genome Biology 12, no. 11 (November 2011): 132, doi:10.1186/gb-2011-12-11-132; Leonardo Salmena et al., “A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?”, Cell 146, no. 3 (August 5, 2011): 353–58, doi:10.1016/j.cell.2011.07.014.

Reprinted with permission by the author
Original article at:

A Critical Reflection on Adam and the Genome, Part 2



When I began college, I signed up for a premed major but quickly changed my course of study after my first biology class. Biology 101 introduced me to the fascinating molecular world inside the cell. At that point, I was hooked. All I wanted was to become a biochemist.

But there was another reason why I gave up on the prospects of becoming a physician. I didn’t think I had the mental wherewithal to make decisions with life and death consequences for patients. And to this day, I deeply admire men and women who do possess that mental fortitude.

The problem is that once someone dies, they don’t come back to life. I knew this reality would loom large for every decision I would make as a physician. Over 100,000 years of human experience teaches that when people die, they remain dead. And this experience is borne out by centuries of scientific study into human biology.

When It Comes to the Virgin Birth and the Resurrection, Christianity is Anti-Scientific

Yet at the heart of the Christian faith is the idea that Jesus Christ was raised from the dead. To be clear: This idea is counter to human experience and thoroughly anti-scientific.

On the other hand, a strong circumstantial case based on historical facts can be marshaled for the life, death, and resurrection of Jesus Christ. The historical evidence for the resurrection combined with the fact that this event transcends the laws of nature is clear evidence for Christians that God intervened in human history to perform a miracle—to act in a way that contravenes the laws of nature.

Even though alternative explanations for the facts surrounding the resurrection fall short, many skeptics remain unconvinced that the resurrection happened. Why? Because it defies scientific explanation—dead people don’t come back to life.

Yet, I don’t know of any evangelical or conservative Christian that would deny the resurrection. Nor would these same Christians deny the virgin birth—another event that also defies scientific explanation. As Christians, we readily embrace anti-scientific ideas when they are central to Christianity. We don’t view them as allegorical or as literary constructs that teach theological truths so that they can be accommodated to scientific truth. We regard them as real events in space and time, in which God discernibly acted in a miraculous way.

Not only are the resurrection and the virgin birth anti-scientific, but the explanations for these two events completely fly in the face of methodological naturalism—the philosophical idea undergirding contemporary science. According to this philosophical system, scientific explanations must rely on material causes—natural process mechanisms. Any explanation that appeals to the work of a supernatural agent—a Creator—or processes that defy known laws of nature can’t be part of the scientific construct. By definition, these types of explanations are forbidden. Yet when it comes to the resurrection and the virgin birth, Christians reject methodological naturalism without apology. We don’t try to force these events within the framework of methodological naturalism by arguing that God used the laws of nature to affect the virgin birth or the resurrection. Why? Because the explanations for these events go beyond nature’s laws—these events are transcendent miracles.

Adam and Eve’s Creation and Importance to the Christian Faith

Should we not be willing to do adopt the same posture when it comes to the question of origins, including the historicity of Adam and Eve?

Like the virgin birth and the resurrection, Adam and Eve’s existence and role as humanity’s founding couple impacts key doctrines of the Christian faith, such as inerrancy, the image of God, the fall, original sin, marriage, and the atonement.

Venema and McKnight’s Adam and the Genome

The importance of a historical Adam and Eve to the Christian faith explains why New testament scholar Scot McKnight (Northern Seminary) spent four chapters—half of a book—in Adam and the Genome trying to convince the reader that the existence of this primordial couple is not critical to the Christian faith. McKnight felt this exercise necessary because he concedes that comparative genomics and population genetics demonstrate the truth of human evolution and the impossibility that humanity arose from a primordial pair—an Adam and an Eve.

Coauthored along with biologist Dennis Venema (Trinity Western University), Adam and the Genome presents a scientific and theological case for evolutionary creationism—the idea that God employed evolutionary processes to bring about the design, origin, and history of life, including humanity.1

The case Venema presents for human evolution serves as the motivation for McKnight’s contribution to the book. In fact, McKnight’s portion of Adam and the Genome is just the latest in a growing list of responses by evangelical and conservative Christian theologians to the specter of human evolution. Though this idea has been in play since the late 1800s with the publication of Darwin’s The Descent of Man, recently, Christian scholars, such as McKnight, feel compelled to sort through the theological fallout of this scientific explanation for human origins because of the emergence of genomics. Now that we have the capability to efficiently sequence and compare the entire genetic makeup of humans and other creatures, such as the great apes, the sense is that the case for human evolution has become undeniable.

So, have Venema and McKnight made their case? Is human evolution a fact? Are Adam and Eve merely theological constructs?

Having left the theological response to McKnight in the hands of scholars such as Gavin Ortlund and Ken Keathley, in part 1 of this review, I offered my reflections on Venema’s intellectual journey from an antievolutionary intelligent design proponent to someone who embraces and now advocates for evolutionary creationism, concluding that it wasn’t scientific evidence alone that motivated Venema and many other evolutionary creationists to adopt this view. I contend that many evolutionary creationists adopt this view, in part, because they are reacting to the disappointment they felt when they realized that they had been unintentionally mislead (when they were young and scientifically naïve) by well-meaning Christians who taught them young-earth creationism. I argue that in abandoning young-earth creationism, many evolutionary creationists have moved to the opposite extreme, rejecting any science-faith model that doesn’t fully embrace mainstream scientific ideas—even if those ideas challenge key biblical doctrines.

In this second part of my review, I offer my thoughts on the core of Venema’s case for human evolution: namely, work in comparative genomics and population genetics, found in chapters two and three, respectively, of Adam and the Genome.

Venema’s goal in his contribution to Adam and the Genome is to communicate the “undeniable” evidence for human evolution. Specifically, Venema discusses recent work in comparative genomics with the hope of explaining to the motivated layperson why many biologists regard the shared features in genomes as evidence for common ancestry. Applying that insight to whole genome comparisons of humans, chimpanzees, and other great apes, Venema explains why biologists think humanity shares an evolutionary history with the great apes—in fact, with all life on Earth. Focusing on pseudogenes, Venema concludes the case for common descent by discussing the widespread occurrence of nonfunctional DNA sequences located throughout the genomes of humans and the great apes—usually in corresponding locations in these genomes. Venema argues that these one-time functional DNA sequence elements were rendered nonfunctional through mutational events and are retained in genomes as vestiges of evolutionary history.

Role of Methodological Naturalism in Venema’s Argument

Admittedly, the scientific case Venema presents for common descent is strong—at least at first glance. (Though, in making his case, he does overlook some significant scientific issues confronting evolutionary biologists, such as the incongruency of evolutionary trees. In other words, evolutionary biologists wind up with different evolutionary trees depending on the region of the genome they use to build the trees. This is certainly the case when the human genome is compared to the genomes of chimpanzees and gorillas. One-third of the human genome more closely aligns to the gorilla genome than to the chimpanzee genome, indicating that gorillas, not chimpanzees, are our closest evolutionary relative.)

Having acknowledged the strong case Venema makes for human evolution, I want to make sure that the reader recognizes the powerful, yet often unrecognized, role methodological naturalism plays, propping up the case for common descent, and, hence, human evolution. Because of the influence of methodological naturalism, the only permissible way to interpret shared genetic features within the mainstream scientific enterprise is from an evolutionary framework. Any explanation evoking a Creator’s involvement is off the table—even if a creation model can account for the data, and it can. However, this approach will never receive a hearing in the scientific community today because it violates the tenets of methodological naturalism. In other words, because of methodological naturalism’s sway, common descent, and, consequently, human evolution must be true by default. No other option is allowed. No other explanation, no matter how valid, is permitted.

Like most evolutionary creationists, Venema and McKnight embrace methodological naturalism when it comes to the question of human origins. Yet they readily reject this idea when it comes to the virgin birth and the resurrection. As a result, their approach to science is inconsistent. Why apply the principles of methodological naturalism to human origins but not to questions surrounding the resurrection or the virgin birth?

It is true that methodological naturalism has a demonstrated track record of success—when it guides investigation of secondary, proximal causes. But this scientific approach often comes up short when scientific questions focus on primary or ultimate causes, such as the origin of the universe or the origin of life.

In fact, I wonder if Christians should embrace methodological naturalism at all. At its essence, this philosophical approach to science is inherently atheistic. A Christian could justify embracing a limited or weak form of methodological naturalism because Scripture teaches that God has providentially instituted processes that operate within the creation to sustain it. When studying these types of phenomena, application of methodological naturalism appears to be justified because the focus is on identifying and characterizing secondary, proximal causes.

But what about the question of origins? Given the descriptions of God’s creative work in the creation accounts, it looks as if God intervened in a direct personal way when it comes to the origin of the universe and the origin and history of life—particularly when it comes to humanity’s beginnings. If so, then methodological naturalism becomes an impotent guide for scientific study because it insists that these events must have mechanistic causes—even if they may not. By default, an atheistic worldview is imposed on the scientific enterprise. Within the framework of methodological naturalism, science no longer becomes the quest for truth, but a game played, with the goal being to produce a material causes explanation for the universe and phenomena within the universe, even if material causes aren’t the true explanation—and even if the explanations leave something to be desired.

Adherents of methodological naturalism defend its restrictions by arguing that science can’t put God in a test tube. Yet it is a straightforward exercise to show that science does have the tool kit to detect the work of intelligent agents within nature and to characterize their capabilities. By extension, science should have no problem detecting a Creator’s handiwork—and even determining the Creator’s identity.

So, what happens if we relax the restrictive requirements of methodological naturalism when we investigate the question of human origins? If we do, it becomes evident that human evolution isn’t unique in its capacity to explain shared genetic features. It becomes conceivable that the shared genetic features in the genomes of humans and the great apes could reflect similar designs employed by a Creator. To put it another way, the shared genetic features could reflect common design, not common descent.

Though this approach to the data is forbidden by contemporary mainstream science, this interpretative approach is not anti-scientific. In fact, there is a historical precedent for viewing shared genetic features as evidence for common design, not common descent. Prior to Darwin, distinguished biologist Sir Richard Owen interpreted shared (homologous) biological structures (and, consequently, related organisms) as manifestations of an archetype that originated in the mind of the First Cause, not the products of descent with modification. Darwin later replaced Owen’s archetype with a common ancestor. Again, the key point is that it is possible to conceive of an alternative interpretation of shared biological features, if one is willing to allow for the operation of a Creator within the history of life.

If the action of an intelligent agent becomes part of the construct of science, and hence, biology, then the shared molecular fossils in the genomes of humans and the great apes (such as pseudogenes) could be seen as shared design features. These sequence elements point to common descent only if certain assumptions are true:

  1. the genomes’ shared structures and sequences are nonfunctional;
  2. the events that created these features are rare, random, and nonrepeatable;
  3. no mechanisms other than common descent (vertical gene transfer) can generate shared features in genomes.

However, recent studies raise questions about the validity of these assumptions. For example, in the last decade or so, molecular biologists and molecular geneticists have discovered that most classes of “junk DNA,” including pseudogenes, have function. (Interested readers can find references to the original scientific papers in the expanded second edition of Who Was Adam? and The Cell’s Design.) In fact, the recently proposed competitive endogenous RNA hypothesis explains why pseudogenes must display similar sequences to their functional counterparts in order to carry out their cellular function.

Moreover, as discussed in Who Was Adam?, researchers are now learning that many of the events that alter genomes’ structures and DNA sequences are not necessarily rare and random. For example, biochemists have known for quite some time that mutations occur in hotspots in genomes. Recent work also indicates that transposon insertion and intron insertion occur at hot spots, and gene loss is repeatable. New studies also reveal that horizontal gene transfer can mimic common descent. This phenomenon is not confined to bacteria and archaea but has been observed in higher plants and animals as well, via a vector-mediated pathway or organelle capture.

These advances serve to undermine key assumptions needed for a common descent argument. Considering these discoveries, is it possible to make sense of the shared genomic architecture and DNA sequences within the framework of a creation model?

A Scientific Creation Model for Common Design

What follows is a brief abstract of the RTB genomics model. A more detailed description and defense of our model can be found in the second expanded edition of Who Was Adam?

A key tenet of the model is the idea that organisms—and hence, their genomes—are the products of God’s direct creative activity. But once created, genomes are subjected to microevolutionary processes.

In brief, our model explains the similarities among organisms’ genomes in one of two ways:

  1. Reflecting the work of a Creator who deliberately designed similar features in genomes according to: (1) a common function, or (2) a common blueprint.
  2. Reflecting the outworking of physical, chemical, or biochemical processes that (1) occur frequently, (2) are nonrandom, and (3) are reproducible. These processes cause the independent origin of the same features in the genomes of different organisms. These features can be either functional or nonfunctional.

Our model also explains genomes’ differences in one of two ways:

  1. Reflecting the work of a Creator who deliberately designed differences in genomes with distinct functions.
  2. Reflecting the outworking of physical, chemical, or biochemical processes that reflect microevolutionary changes.

In principle, our model can account for similarities and differences in the genomes of organisms as either the deliberate work of a Creator or via natural-process mechanisms that alter the genomes after creation.

Were Adam and Eve Real?

Having argued for the reality of human evolution, Venema focuses attention on Adam and Eve’s historicity. If humanity arose through an evolutionary process, then Venema rightly points out that humanity must have begun as a population, not a primordial couple—by definition. According to evolutionary biologists: evolution is a population-level phenomenon. That being the case, if humanity arose via evolutionary processes, then there could never have been an Adam and an Eve. In support of this idea, Venema then discusses population genetics studies that indicate humanity began as an initial group of around 10,000 individuals. Based on these methods, the genetic diversity among humans today is too great to have come from just two individuals. Venema then goes on to explain how evolutionary biologists reconcile the existence of Mitochondrial Eve and Y-chromosomal Adam (understood to be an actual woman and man, respectively) with the idea that humanity began as a population.

Some Thoughts on Methods Used to Estimate Humanity’s Initial Population Size

Did humanity originate from a primordial pair?

One point Venema fails to acknowledge is that, at best, the population sizes generated from genetic diversity data are merely estimates, not hard and fast values. The reason: the mathematical models these methods are based on are highly idealized, generating differing estimates based on several factors.

More significantly, recent studies focusing on birds and mammals, however, raise questions as to whether these models predict population size. As the author of one study states, “Analyses of mitochondrial DNA (mtDNA) have challenged the concept that genetic diversity within populations is governed by effective population size and mutation rate . . . the variation in the rate of mutation rather than in population size is the main explanation for variations in mtDNA diversity observed among bird species.”2

In fact, several studies—involving white-tail deer, mouflon sheep, Przewalski’s horses, white-tail eagles, the copper redhorse, and gray whales—in which the original population size was known, the measured genetic diversity generations later was much greater than expected based on the models. In turn, if this data was used to estimate initial population size, the numbers would be much greater than the models predicted.

Did humanity originate from a single pair? Even though population estimates indicate humanity originated from several hundred to several thousand individuals based on mathematical models, it could well be that these numbers overestimate the original numbers for the first humans. And given how poorly these population size models perform, it is hard to argue that science has falsified the notion that humanity descended from a primordial pair.

Final Thoughts

In Adam and the Genome, Venema makes a compelling case for human evolution, but he fails to tell the entire story. Venema overlooks a serious problem facing the evolutionary paradigm: namely, the incongruencies of evolutionary trees built from genetic data. He also neglects to communicate a legion of exciting discoveries made since the human genome sequence was completed—discoveries indicating that virtually every class of junk DNA has function. These discoveries undermine evolution’s case and make it apparent that we are in our infancy when it comes to understanding the structure and function of the human genome. The more we learn, the more evident its elegant and ingenious design.

At the end of the day, the case for human evolution is propped up by the restrictions of methodological naturalism. As we have demonstrated in Who Was Adam?, when this restriction is relaxed, it is possible to advance a competing creation model that can account for the data from comparative genomics.

One thing has become clear to me after reading Adam and the Genome. It is no longer effective for creationists and intelligent design proponents to focus our efforts on taking pot shots at human evolution. We must move beyond that type of critique and develop a philosophically robust framework for science that can compete with methodological naturalism and advance scientific models within that new framework with the capacity of explaining the data from comparative genomics and population genetics.

I am confident we can. We simply must roll up our sleeves and get to work.

Resources—Theological Reflections on Adam and the Genome

Resources—An Old-Earth Creationist Perspective on the Scientific Case for a Traditional Biblical View of Human Origins

Resources—The Problem of Incongruent Evolutionary Trees

Resources—Science Can Detect the Creator’s Handiwork in Nature

Resources—Common Design as a Valid Scientific Model

Resources—Junk DNA is Functional

Resources—Pseudogenes are Functional

Resources—Mutational Hot Spots in Genomes

Resources—Adam and Eve’s Historicity


  1. Dennis R. Venema and Scot McKnight, Adam and the Genome: Reading Scripture after Genetic Science (Grand Rapids, MI: Brazos Press, 2017).
  2. Hans Ellegren, “Is Genetic Diversity Really Higher in Large Populations?” Journal of Biology 8 (April 2009): 41, doi:10.1186/jbiol135.
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Protein-Binding Sites ENCODEd into the Design of the Human Genome



At last year’s AMP Conference, I delivered a talk titled: “How the Greatest Challenges Can Become the Greatest Opportunities for the Gospel.” I illustrated this point by describing three scientific concepts related to the origin of humanity that 20 years ago stood as insurmountable challenges to the traditional biblical view of human origins. But, thanks to scientific advances, these concepts have been replaced with new insights that turn these challenges into evidence for the Christian faith.

The Challenge of Junk DNA

One of the challenges I discussed centered on junk DNA—nonfunctional DNA littering the genomes of most organisms. Presumably, these nonfunctional DNA sequences arose through random biochemical, chemical, and physical events, with functional DNA converted into useless junk, in some instances. In fact, when the scientific community declared the human genome sequence completed in 2003, estimates at that time indicated that around 95 percent of the human genome consist of junk sequences.

Since I have been involved in apologetics (around 20 years), skeptics (and believers) have regarded the high percentages of junk DNA in genomes as a significant problem for intelligent design and creation models. Why would an all-powerful, all-knowing, and all-good God create organisms with so much junk in their genomes? The shared junk DNA sequences found among the genomes of humans and the great apes compounds this challenge. For many, these shared sequences serve as compelling evidence for common ancestry among humans and the other primates. Why would a Creator introduce nonfunctional DNA sequences into corresponding locations in genomes of humans and the great apes?

But what if the junk DNA sequences are functional? It would undermine the case for common descent, because these shared sequences could reasonably be interpreted as evidence for common design.

The ENCODE Project

In recent years, numerous discoveries indicate that virtually every class of junk DNA displays function, providing mounting support for a common-design interpretation of junk DNA. (For a summary, see the expanded and updated edition of Who Was Adam?) Perhaps the most significant advance toward that end came in the fall of 2012 with the publication of phase II results of the ENCODE project—a program carried out by a consortium of scientists with the goal of identifying the functional DNA sequence elements in the human genome.

To the surprise of many, the ENCODE project reported that around 80 percent of the human genome displays function, with the expectation that this percentage should increase with phase III of the project. Many of the newly recognized functional elements play a central role in regulating gene expression. Others serve critical roles in establishing and maintaining the three-dimensional hierarchical structure of chromosomes.

If valid, the ENCODE results would force a radical revision of the way scientists view the human genome. Instead of a wasteland littered with junk DNA sequences, the human genome (and the genome of other organisms) would have to be viewed as replete with functional elements, pointing to a system far more complex and sophisticated than ever imagined—befitting a Creator’s handiwork. (See the articles listed in the Resources section below for more details.)

ENCODE Skeptics

Within hours of the publication of the phase II results, evolutionary biologists condemned the ENCODE project, citing a number of technical issues with the way the study was designed and the way the results were interpreted. (For a response to these complaints go herehere, and here.)

These technical complaints continue today, igniting the junk DNA war between evolutionary biologists and genomics scientists. Though the concerns expressed by evolutionary biologists are technical, some scientists have suggested the real motivation behind the criticisms of the ENCODE project are philosophical—even theological—in nature. For example, molecular biologists John Mattick and Marcel Dinger write:

There may also be another factor motivating the Graur et al. and related articles (van Bakel et al. 2010; Scanlan 2012), which is suggested by the sources and selection of quotations used at the beginning of the article, as well as in the use of the phrase ‘evolution-free gospel’ in its title (Graur et al. 2013): the argument of a largely non-functional genome is invoked by some evolutionary theorists in the debate against the proposition of intelligent design of life on earth, particularly with respect to the origin of humanity. In essence, the argument posits that the presence of non-protein-coding or so-called ‘junk DNA’ that comprises >90% of the human genome is evidence for the accumulation of evolutionary debris by blind Darwinian evolution, and argues against intelligent design, as an intelligent designer would presumably not fill the human genetic instruction set with meaningless information (Dawkins 1986; Collins2006). This argument is threatened in the face of growing functional indices of noncoding regions of the genome, with the latter reciprocally used in support of the notion of intelligent design and to challenge the conception that natural selection accounts for the existence of complex organisms (Behe 2003; Wells 2011).1

Is DNA-Binding Activity Functional?

Even though there may be nonscientific reasons for the complaints leveled against the ENCODE project, it is important to address the technical concerns. One relates to how biochemical function was determined by the ENCODE project. Critics argued that ENCODE scientists conflated biochemical activity with function. As a case in point, three of the assays employed by the ENCODE consortium measure binding of proteins to the genome, with the assumption that binding of transcription factors and histones to DNA indicated a functional role for the target sequences. On the other hand, ENCODE skeptics argue that most of the measured protein binding to the genome was random.

Most DNA-binding proteins recognize and bind to short stretches of DNA (4 to 10 base pairs in length) comprised of highly specific nucleotide sequences. But given the massive size of the human genome (3.2 billion genetic letters), nonfunctional binding sites will randomly occur throughout the genome, for statistical reasons alone. To illustrate: Many DNA-binding proteins target roughly between 1 and 100 sites in the genome. Yet, the genome potentially harbors between 1 million and 1 billion binding sites. The hundreds of sites that are slight variants of the target sequence will have a strong affinity to the DNA-binding proteins, with thousands more having weaker affinities. Hence, the ENCODE critics maintain that much of the protein binding measured by the ENCODE team was random and nonfunctional. To put it differently, much of the protein binding measured in the ENCODE assays merely is a consequence of random biochemical activity.

Nonfunctional Protein Binding to DNA Is Rare

This challenge does have some merit. But, this criticism may not be valid. In an earlier response to this challenge, I acknowledged that some protein binding in genomes will be random and nonfunctional. Yet, based on my intuition as a biochemist, I argued that random binding of proteins throughout the genome would be disruptive to DNA metabolism, and, from an evolutionary perspective would have been eliminated by natural selection. (From an intelligent design/creation model vantage point, it is reasonable to expect that a Creator would design genomes with minimal nonfunctional protein-binding sites.)

As it happens, new work by researchers from NYU affirms my assessment.2 These investigators demonstrated that protein binding in genomes is not random but highly specific. As a corollary, the human genome (and genomes of other organisms) contains very few nonfunctional protein-binding sites.

To reach this conclusion, these researchers looked for nonfunctional protein-binding sites in the genomes of 75 organisms, representative of nearly every major biological group, and assessed the strength of their interaction with DNA-binding proteins. The researchers began their project by measuring the binding affinity for a sample of regulatory proteins (from humans, mice, fruit flies, and yeast) with every possible 8 base pair sequence combination (32,896). Based on the binding affinity data, the NYU scientists discovered that nonfunctional binding sites with a high affinity for DNA binding proteins occurred infrequently in genomes. To use scientific jargon to describe their findings: The researchers discovered a negative correlation between protein-binding affinity and the frequency of nonfunctional binding sites in genomes. Using statistical methods, they demonstrated that this pattern holds for all 75 genomes in their study.

They attempted to account for the frequency of nonfunctional binding sequences in genomes by modeling the evolutionary process, assuming neutral evolution in which random mutations accrue over time free from the influence of natural selection. They discovered that this modeling failed to account for the sequence distributions they observed in the genomes, concluding that natural selection must have weeded high affinity nonfunctional binding sites in genomes.

These results make sense. The NYU scientists point out that protein mis-binding would be catastrophic for two reasons: (1) it would interfere with several key processes, such as transcription, gene regulation, replication, and DNA repair (the interference effect); and (2) it would create inefficiencies by rendering DNA-binding proteins unavailable to bind at functional sites (the titration effect). Though these problems may be insignificant for a given DNA-binding protein, the cumulative effects would be devastating because there are 100 to 1,000 DNA-binding proteins per genome with 10 to 10,000 copies of each protein.

The Human Genome Is ENCODEd for Design

Though the NYU researchers conducted their work from an evolutionary perspective, their results also make sense from an intelligent design/creation model vantage point. If genome sequences are truly the product of a Creator’s handiwork, then it is reasonable to think that the sequences comprising genomes would be optimized—in this case, to minimize protein mis-binding. Though evolutionary biologists maintain that natural selection shaped genomes for optimal protein binding, as a creationist, it is my contention that the genomes were shaped by an intelligent Agent—a Creator.

These results also have important implications for how we interpret the results of the ENCODE project. Given that the NYU researchers discovered that high affinity nonfunctional binding sites rarely occur in genomes (and provided a rationale for why that is the case), it is difficult for critics of the ENCODE project to argue that transcription factor and histone binding assays were measuring mostly random binding. Considering this recent work, it makes most sense to interpret the protein-binding activity in the human genome as functionally significant, bolstering the original conclusion of the ENCODE project—namely, that most of the human genome consists of functional DNA sequence elements. It goes without saying: If the original conclusion of the ENCODE project stands, the best evidence for the evolutionary paradigm unravels.

Our understanding of genomes is in its infancy. Forced by their commitment to the evolutionary paradigm, many biologists see genomes as the cobbled-together product of an unguided evolutionary history. But as this recent study attests, the more we learn about the structure and function of genomes, the more elegant and sophisticated they appear to be. And the more reasons we have to believe that genomes are the handiwork of our Creator.



  1. John S. Mattick and Marcel E. Dinger, “The Extent of Functionality in the Human Genome,” The HUGO Journal 7 (July 2013): doi:10.1186/1877-6566-7-2.
  2. Long Qian and Edo Kussell, “Genome-Wide Motif Statistics Are Shaped by DNA Binding Proteins over Evolutionary Time Scales,” Physical Review X 6 (October–December 2016): id. 041009, doi:10.1103/PhysRevX.6.041009.
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The Logic of DNA Replication Makes a Case for Intelligent Design



Why do I think God exists?

In short: The elegance, sophistication, and ingenuity of biochemical systems—and their astonishing similarity to man-made systems—convinces me that God is responsible for life’s origin and design.

While many skeptics readily acknowledge the remarkable designs of biochemical systems, they would disagree with my conclusion about God’s existence. Why? Because for every biochemical system I point to that displays beauty and elegance, they can point to one that seems to be poorly designed. In their view, these substandard designs reflect life’s evolutionary origin. They argue that evolutionary mechanisms kludged together the cell’s chemical systems through a historically contingent process that co-opted preexisting systems, cobbling them together to form new biochemical systems.

According to skeptics, one doesn’t have to look hard to find biochemical systems that seem to have been put together in a haphazard manner, and DNA replication appears to be an example of this. In many respects, DNA replication lies at the heart of the cell’s chemical operations. If designed by a Creator, this biochemical system, above all others, should epitomize intelligent design. Yet the DNA replication process appears to be unwieldy, inefficient, and unduly complex—the type of system evolution would generate by force, not the type of system worthy to be designated the product of the Creator’s handiwork.

Yet new work by Japanese researchers helps explain why DNA replication is the way it is.1Instead of reflecting the cumbersome product of an unguided evolutionary history, the DNA replication process displays an exquisite molecular logic.

To appreciate the significance of the Japanese study and its implication for the creation/evolution controversy, a short biochemistry primer is in order. For readers who are familiar with DNA’s structure and the DNA replication process, you can skip the next two sections.


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).


Image 1: Adenosine Monophosphate, a Nucleotide

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.

Image 2: The DNA Backbone

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.

DNA Replication

Biochemists refer to DNA replication as a template-directed, semi-conservative process. By template-directed, biochemists mean that the nucleotide sequences of the “parent” DNA molecule function as a template, directing the assembly of the DNA strands of the two “daughter” molecules. By semi-conservative, biochemists mean that after replication, each daughter DNA molecule contains one newly formed DNA strand and one strand from the parent molecule.


Image 3: Semi-Conservative DNA Replication

Conceptually, template-directed, semi-conservative DNA replication entails the separation of the parent DNA double-helix into two single strands. By using the base-pairing rules, each strand serves as a template for the cell’s machinery to use when it forms a new DNA strand with a nucleotide sequence complementary to the parent strand. Because each strand of the parent DNA molecule directs the production of a new DNA strand, two daughter molecules result. Each one possesses an original strand from the parent molecule and a newly formed DNA strand produced by a template-directed synthetic process.

DNA replication begins at specific sites along the DNA double helix, called replication origins. The DNA double helix unwinds locally at the origin of replication to produce what biochemists call a replication bubble. The bubble expands in both directions from the origin during the course of DNA replication. Once the individual strands of the DNA double helix unwind and are exposed within the replication bubble, they are available to direct the production of the daughter strand. The site where the DNA double helix continuously unwinds is called the replication fork. Because DNA replication proceeds in both directions away from the origin, there are two replication forks within each bubble.


Image 4: DNA Replication

DNA replication can only proceed in a single direction, from the top of the DNA strand to the bottom. Because the strands that form the DNA double helix align in an antiparallel fashion with the top of one strand juxtaposed to the bottom of the other strand, only one strand at each replication fork has the proper orientation (bottom-to-top) to direct the assembly of a new strand, in the top-to-bottom direction. For this strand—referred to as the “leading strand”—DNA replication proceeds rapidly and continuously in the direction of the advancing replication fork.

DNA replication can’t proceed along the strand with the top-to-bottom orientation until the replication bubble has expanded enough to expose a sizable stretch of DNA. When this happens, DNA replication moves away from the advancing replication fork. DNA replication can only proceed a short distance for the top-to-bottom oriented strand before the replication process has to stop and wait for more of the parent DNA strand to be exposed. When a sufficient length of the parent DNA template is exposed for a second time, DNA replication can proceed again, but only briefly before it has to stop again and wait for more DNA to be exposed. The process of discontinuous DNA replication takes place repeatedly until the entire strand is replicated. Each time DNA replication starts and stops, a small fragment of DNA is produced. Biochemists refer to these pieces of DNA (that will eventually comprise the daughter strand) as “Okazaki fragments,” named after the biochemist who discovered them. Biochemists call the strand produced discontinuously the “lagging strand,”because DNA replication for this strand lags behind the more rapidly produced leading strand.

One additional point: The leading strand at one replication fork is the lagging strand at the other replication fork, since the replication forks at the two ends of the replication bubble advance in opposite directions.

Before the newly formed daughter strands can be produced, a small RNA primer must be produced. The protein that synthesizes new DNA by reading the parent DNA template strand—DNA polymerase—can’t start production from scratch. It has to be primed. A massive protein complex, called the primosome, which consists of more than 15 different proteins, produces the RNA primer needed by DNA polymerase.

Once primed, DNA polymerase will continuously produce DNA along the leading strand. However, for the lagging strand, DNA polymerase can only generate DNA in spurts to produce Okazaki fragments. Each time DNA polymerase generates an Okazaki fragment, the primosome complex must produce a new RNA primer.

Once DNA replication is completed, the RNA primers are removed from the continuous DNA of the leading strand and the Okazaki fragments that make up the lagging strand. A protein called a 3’–5’ exonuclease removes the RNA primers. A different DNA polymerase fills in the gaps created by the removal of the RNA primers. Finally, a protein called a ligase connects all the Okazaki fragments together to form a continuous piece of DNA out of the lagging strand.

DNA Replication and the Case for Evolution

This cursory description of DNA replication clearly illustrates the complexity of this biochemical operation. (Many details of the process were left out of the discussion.) This description also reveals why biochemists view this process as cumbersome and unwieldy. There is no obvious reason why DNA replication proceeds as a semi-conservative, RNA primer-dependent, unidirectional process involving leading and lagging strands to produce DNA daughter molecules. Because of this uncertainty, skeptics view DNA replication as a chance outcome of a historically contingent process, kludged together from the biochemical leftovers of the RNA world.

If there is one feature of DNA replication that is responsible for the complexity of the process, it is the directionality of DNA replication—from top to bottom. At first glance, it would seem as if the process would be simpler and more elegant if replication could proceed in both directions. Skeptics argue that the fact that it doesn’t reflects the evolutionary origin of the replication process.

Yet work by the team from Sapporo, Japan indicates that there is an exquisite molecular rationale for the directionality of DNA replication.

Why DNA Replication Proceeds in a Single Direction

These researchers recognized an important opportunity to ask why DNA replication proceeds only in a single direction with the discovery of a class of enzymes that add nucleotides to the ends of transfer RNA (tRNA) molecules. (tRNA molecules ferry amino acids to the ribsosome during protein synthesis.) If damaged, tRNA molecules cannot properly carry out their role in protein production. Fortunately, there are repair enzymes that can fix damaged tRNA molecules. One of them is called Thg-1-like protein (TLP).

TLP adds nucleotides to damaged ends of tRNA molecules. But instead of adding the nucleotides top to bottom, the enzyme adds these subunit molecules to the tRNA bottom to top, the opposite direction of DNA replication.

By determining the mechanism employed by TLP during bottom-to-top nucleotide addition, the researchers gained important insight into the constraints of DNA replication. As it turns out, bottom-to-top addition is a much more complex process than the normal top-to-bottom nucleotide addition. Bottom-to-top addition is a cumbersome two-step process that requires an enzyme with two active sites that have to be linked together in a precise way. In contrast, top-to-bottom addition is a simple, one-step reaction that proceeds with a single active site. In other words, DNA replication proceeds in a single direction (top-to-bottom) because it is mechanistically simpler and more efficient.

One could argue that the complexity that arises by the top-to-bottom DNA replication process is a trade-off for a mechanistically simpler nucleotide addition reaction. Still, if DNA replication proceeded in both directions the process would be complex and unwieldy. For example, if replication proceeded in two directions, the cell would require two distinct types of primosomes and DNA polymerases, one set for each direction of DNA replication. Employing two sets of primosomes and DNA polymerases is clearly less efficient than employing a single set of enzymes.

Ironically, if DNA replication could proceed in two directions, there still would be a leading and a lagging strand. Why? Because bottom-to-top replication is a two-step process and would proceed more slowly than the single step of top-to-bottom replication. In other words, the assembly of the DNA strand in a bottom-to-top direction would lag behind the assembly of the DNA strand that traveled in a top-to-bottom direction.

Bidirectional DNA replication would also cause another complication due to a crowding effect. Once the replication bubble opens, both sets of replication enzymes would have to fit into the replication bubble’s constrained space. This molecular overcrowding would further compromise the efficiency of the replication process. Overcrowding is not an issue for unidirectional DNA replication that proceeds in a top-to-bottom direction.

The bottom line: In light of this new insight, it is hard to argue that DNA replication has been cobbled together via a historically contingent pathway. Instead, it is looking more and more like a process ingenuously designed by a Divine Mind.

The Cell’s Design: How Chemistry Reveals the Creator’s Artistry by Fazale Rana (book)
DNA Soaks Up Sun’s Rays” by Fazale Rana (article)
DNA: Designed for Flexibility” by Fazale Rana (article)
How the Central Dogma of Molecular Biology Points to Design” by Fazale Rana (article)
Why I Believe God Exists: Evidences from a Biochemist” by Fazale Rana (video)

  1. Shoko Kimura et al., “Template-Dependent Nucleotide Addition in the Reverse (3’–5’) Direction by Thg1-like Protein,” Science Advances 2 (March 2016): e1501397, doi:10.1126/sciadv.1501397.
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