It is perhaps the most remarkable turnaround in human history.
Saul of Tarsus, a Pharisee, a Hebrew’s Hebrew, a student of Gamaliel—the one who helped persecute the first Christians—became Paul the Apostle, the one who helped take the gospel to the Gentiles. Paul’s dramatic change of perspective occurred because of his Damascus Road experience, in which he had a supernatural encounter with Christ.
From my perspective as a life scientist, many scientists are going through their own type of “Damascus Road” experience regarding “junk” DNA. Since the 1970s, biologists have viewed most of the eukaryotic genome as composed of useless, nonfunctional DNA sequence elements. These elements were interpreted as the outworking of haphazard biochemical events that left their mark on the genomes of existing organisms as vestiges of life’s evolutionary history. Yet, in recent years, a growing body of evidence demonstrates that much, if not nearly all, of the genome consists of functional DNA sequence elements, rendering the concept of junk DNA obsolete.
Unlike Paul’s startling conversion—which occurred suddenly when he heard Jesus ask him, “Saul, Saul, why do you persecute me?”—the about-face by life scientists has come slowly and methodically as unexpected evidence for the utility of every class of junk DNA has accrued over the last 20 years.
Not long ago, most biologists would have ignored the so-called junk DNA sequences in genomes. Today, biologists now deliberately and systematically investigate the different types of junk DNA sequences to understand their function. In fact, biomedical researchers are now looking for ways to take advantage of this growing understanding of junk DNA’s physiological roles to diagnose and treat diseases.
The change in perspective regarding endogenous retroviruses (ERVs) exemplifies this about-face.
ERVs bear strong sequence similarity to retroviruses. But because these genetic sequences are found in genomes, biologists have deemed them to be the leftover genetic remnants of retroviral infections. Accordingly, if the retroviral infection occurs in germ cells, the virus can be passed on to subsequent generations. For this reason, evolutionary biologists use the distribution of ERV sequences in genomes to determine evolutionary relationships among organisms.
In recent years, however, biologists have discovered that ERVs and DNA elements presumably derived from ERVs, such as long terminal repeats (LTRs) serve a variety of critical roles. LTRs play a role in regulating gene expression. And ERVs play an active role in the innate immune system (among other things). This role vitally depends on the sequence similarity between ERVs and retroviral nucleotide sequences.
The importance of ERVs in genomes has been highlighted by recently published work from a research team headed by an investigator from Cornell University.1 These molecular biologists add insight into the benefits provided by transcribed retroviral-like sequences and their protein products. The transcripts and their translated protein products protect early-stage human embryos and the placenta from retroviral infections through a mechanism called competitive inhibition.
This discovery has important scientific and biomedical implications, giving us a deeper understanding about genome biology and ways to protect and treat people with viral diseases.
It also has important ramifications for scientists who view the human genome (and the genomes of other organisms) from a design/creation model perspective. Advances in our understanding of the functions served by ERVs offer justification for the conviction that human beings are the product of a Creator’s handiwork. Accordingly, we would expect that the human genome (and genomes of other organisms) must display design signatures.
Before we discuss the Cornell team’s work and its implications for the design argument, a quick primer on retroviruses and ERVs might be helpful. If you don’t need the primer, feel free to skip ahead to ERV Expression Produces Suppressyn, Protecting Early-Stage Embryos.
Like all viruses, retroviruses consist of genetic material surrounded by a protein capsid. In turn, the protein capsid is surrounded by an envelope made of a lipid bilayer. Embedded in the bilayer are viral envelope proteins. Retroviruses infect organisms by invading specific cell types of the host organism. They attach to the target cell’s surface through interactions between envelope proteins and host proteins located at the cell surface. These host proteins are referred to as receptors, though they normally perform other functions for the cell. Once this binding event takes place, the targeted cell engulfs the retrovirus. Once engulfed, the retroviral capsid disassembles, and the viral genetic material exploits the host cell’s machinery to produce copies of itself and to generate viral proteins. These biomolecules then assemble into new viral particles. When the newly formed viruses escape from the invaded cell into the extracellular space, the infection cycle repeats.
Because the genetic material of retroviruses is RNA, it is converted into DNA as part of the infectious cycle. This conversion is carried out by an enzyme called reverse transcriptase, which is delivered to the target cell along with the retroviral RNA. The enzyme uses the retroviral RNA to make DNA. The newly made DNA can then use the invaded cell’s biosynthetic pathways to direct the production of new retroviral particles. The DNA copy of the retroviral genetic material can also become incorporated into the host cell’s genome through the activity of an enzyme known as an integrase. When this insertion takes place, the retroviral DNA becomes part of the host cell’s genome. This process is called endogenization.
Endogenous Retroviruses (ERVs)
Once retroviral DNA becomes incorporated into an organism’s genome it is called an endogenous retrovirus (in contradistinction to exogenous retroviruses, which exist independently of genomes). After inserting into the host’s genome, the endogenous retrovirus can still produce retroviral particles if its DNA is transcribed by the host cell’s biochemical machinery.
If the ERV infects a germ line cell (a sperm cell or an egg cell), it can be inherited and transmitted from generation to generation as a permanent feature of the genome. If the ERV DNA suffers severe mutations, it becomes disabled and remains in the genome to become nonfunctional, junk DNA.
Endogenous Retroviruses and the Case for Human Evolution
Many human ERVs are also found in the genomes of chimpanzees, bonobos, gorillas, and orangutans. Not only do these ERVs share many of the same sequence patterns, but they also appear in corresponding locations in the genomes.
Evolutionary biologists explain this data by assuming that the shared ancestor of humans and chimpanzees, for example, became infected by these specific retroviruses. Later, these endogenized retroviruses experienced mutations that disabled them in the ancestor’s genome.
The ERV sequences were retained in the genomes of humans and chimpanzees as their separate evolutionary lineages diverged from the common ancestor. According to the evolutionary model, the shared endogenous retroviruses represent the molecular artifacts of infections that occurred millions of years ago and left their imprint on contemporary genomes via this (presumed) shared ancestry.
Given this scenario, evolutionary biologists traditionally regarded ERVs as nonfunctional junk sequences. Yet, life scientists have uncovered something unexpected about ERV sequences. ERVs play several critical roles, including offering innate immunity against viral infections. These findings complicate the evolutionary narrative about ERVs.
ERV Expression Produces Suppressyn, Protecting Early-Stage Embryos
Based on early studies, which demonstrated that ERVs contribute to the innate immune system, the Cornell team sought to specifically understand the role that ERV-encoded envelope proteins might play in protecting human cells from retroviral infections. Studies using animal models indicated that ERV-envelope proteins have an antiviral role. The team wondered if this is the case for humans.
As a first step, the research team scanned the human genome for genes that encode proteins that resemble retroviral envelope proteins. They discovered around 1,500 of these types of genes. Of them, about half are transcribed. Many of these genes are expressed at low levels in most tissues, but they are expressed at high levels in sperm and egg cells, in early-stage embryos, and in the cells that form the placenta. Often, expression of these genes in the placenta occurs throughout the course of the pregnancy.
The research team discovered that one of the envelope-like proteins expressed is suppressyn. This protein is known to bind to the amino acid transport protein ASCT2, which is located on the cell surface. The ASCT2 protein also serves as a “receptor” for certain types of retroviruses.
Because of its gene expression profile and its interaction with ASCT2, the molecular biologists decided to study suppressyn, treating this protein as paradigmatic for the physiological activity of the envelope-like proteins found in the human genome.
The research team demonstrated that the suppressyn protein inhibits retroviral infections of human cells in culture. They speculate that when suppressyn is produced, it either:
- interacts with the ASCT2 protein during the receptor’s biosynthesis, preventing it from decorating the cell surface, or
- makes its way to the extracellular space, where it binds to ASCT2, preventing retrovirus virions from binding to the host cell’s surface.
Both events would protect the host cell from retroviral infections through a process called competitive inhibition. The team concludes that one role for envelope-like proteins found in the human genome is protection from retroviral infections. The high level of gene expression during the early stages of embryonic development protects the developing embryo at a stage when it is particularly vulnerable.
This study is not the first one to identify an antiviral role for genes in the human genome that bear similarity to retroviral genes.
ERVs Protect Vulnerable Early-Stage Embryos from Viruses
As a case in point, in 2015 researchers from Stanford University showed that a class of ERVs in the human genome (HERV-K) becomes transcriptionally active during the 8-cell stage of human embryos and protects them from viral infection by hampering the interaction of virions with the cell membrane.2
The transcribed ERVs inhibit retroviral infections through three distinct processes.
- The ERV transcripts interact with retroviral genetic material, blocking retroviral infections through an antisense mechanism.
- The ERV transcripts competitively inhibit the assembly of new retroviral particles.
- The translation of ERV transcripts produces proteins that will block the retroviral life cycle through competitive inhibition—in a similar vein to the action of suppressyn.
For example, gag-like proteins are produced from these ERV transcripts. The gag proteins form the retroviral nucleocapsid that encapsulates retroviral genetic material. The gag-like proteins encoded in the human genome would competitively inhibit the assembly of the retroviral nucleocapsid.
In short, the ERV sequences in genomes contribute to innate immunity through an elegant and ingenious mechanism. This protection appears to be prominent in early-stage embryos and cells that form the placenta.
A Scientific Turnaround
The growing evidence for ERV function is part of an amassing body of evidence that so-called junk DNA has function. This evidence has convinced most life scientists that a significant fraction of the genome contains functional sequences. As Francis Collins, former head of the Human Genome Project, and later, the National Institutes of Health, stated:
“There were long stretches of DNA in between genes that didn’t seem to be doing very much; some even referred to these as ‘junk DNA,’ though a certain amount of hubris was required for anyone to call any part of the genome ‘junk,’ given our level of ignorance.”3
Though we have had the human genome sequence since 2000, it’s safe to say that we’re still in our infancy in terms of understanding the human genome. And it is becoming clear that as scientific understanding of the genome matures, we are discovering a remarkable level of biochemical activity associated with the various sequence elements of the genome that contribute to genome function.
The conclusion that the genome consists mostly of junk DNA also reflects a deep-seated commitment to an evolutionary perspective on the genome. This view asserts that the genomes of organisms have been assembled through the accrual of DNA sequence elements in a haphazard manner, with many of the sequences serving no useful function.
Yet, as evidence mounts that so-called junk DNA sequences such as ERVs display vital function, it opens the possibility for another explanation for the structure and function of genomes based on a creation model approach.
Can the Occurrence of ERVs Be Explained from a Creation Model Perspective?
For those who advocate for ID or a creation model approach to biology, two troubling questions arise:
Why would the Creator introduce ERV sequence elements in the same locations within the genomes of organisms that naturally group together (based on other biological features)? And why would he create these shared sequence elements to bear such strong similarity to retroviruses?
For many people, the presence and distribution of ERV sequences in genomes provides indisputable evidence for human evolution and our shared ancestry with the great apes. How is it possible to account for ERVs in genomes from an intelligent design/creation model perspective?
To do so, at minimum the ID/creation model must:
- Find evidence that ERVs are functional
- Account for the sequence similarity between ERVs and retroviruses
- Explain their shared distribution in the genomes of organisms that naturally cluster together
ERVs in a Creation Model
The results from this latest study—and others (see the Resource section)—easily satisfy the first two criteria. But what about the distribution of ERVs in the genomes of organisms that naturally cluster together into nested hierarchies?
It’s true that most life scientists regard shared biological features—including DNA sequences—as evidence for their shared evolutionary ancestry. Yet, an alternative explanation for biological similarities can be advanced. Instead of evincing common descent, they could be interpreted as shared biological designs with the mutual features reflecting manifestations of a common blueprint—an archetype that arises out of the Creator’s mind. From a creation model perspective, the genetic similarities in the genomes of humans and the great apes—including DNA sequence elements such as ERVs—have been intentionally introduced by the Creator.
To be clear, the Cornell research team views the genomes of humans, great apes, and old-world monkeys as the product of evolution. Yet, they provide an explanation for the distribution of the suppressyn gene in these three sets of genomes that comfortably aligns with a creation model perspective. They write:
“These data indicate that SUPYN [suppressyn] antiviral activity against RDRenv-mediated infection is an ancestral trait that has been preserved over ~20 million years of hominoid evolution.”4
In other words, they interpret the occurrence and retention of the suppressyn gene in humans and great apes (shared distribution) in terms of its functional utility. With all three criteria satisfied, the creation model approach to genomes gains legitimacy.
As a life scientist, it is remarkable to me how much things have changed in the last couple of decades. Twenty years ago, it was hard to imagine why junk DNA was found at such high levels in genomes if God had intervened in a direct way to create life on Earth. The about-face made by life scientists regarding the structure and function of genomes is reminiscent of Saul’s conversion to Christianity.
Yet, so many people are unaware of this changed perspective. It’s up to those of us with this awareness to take the “junk” DNA gospel to Jerusalem, Judea, Samaria, and the ends of the earth.
- Thinking about Evolution: 25 Questions Christians Want Answered by Anjeanette Roberts, Fazale Rana, Sue Dykes, and Mark Perez (book)
- Who Was Adam? A Creation Model Approach to the Origin of Humanity, 2nd exp. ed., by Fazale Rana with Hugh Ross (book)
- The Cell’s Design: How Chemistry Reveals the Creator’s Artistry by Fazale Rana (book)
LTRs Have Function
- “Is Junk DNA Evidence for Biological Evolution?” by Fazale Rana (article)
- “Does Retroviral DNA Insert Randomly into Genomes?” by Fazale Rana (article)
Endogenous Retroviruses Have Function
- “Koala Endogenous Retroviruses (ERVs) Protect against Retroviral Infections” by Fazale Rana (article)
- “SARS-CoV-2 Biology Points to Endogenous Retrovirus Design” by Fazale Rana (article)
- “Endogenous Retroviruses (ERVs) Protect Early-Stage Human Embryos” by Fazale Rana (article)
- “Endogenous Viral Elements (EVEs) Help Wasps to Parasitize” by Fazale Rana (article)
- “Endogenous Retroviruses Help Fight Tumors” by Fazale Rana (article)
- “Endogenous Retrovirus Expression Evinces Design” by Fazale Rana (article)
- “Questioning Evolutionary Presuppositions about Endogenous Retroviruses” by Anjeanette Roberts (article)
- “A Common Design View of ERVs Encourages Scientific Investigation” by Anjeanette Roberts (article)
The Historical and Philosophical Case for Common Design
- “Archetype or Ancestor? Sir Richard Owen and the Case for Design” by Fazale Rana (article)
- “Duck-Billed Platypus Venom: Designed for Discovery” by Fazale Rana (article)
- “Does Old-Earth Creationism Make God Deceptive?” by Fazale Rana (article)
The Negative Impact of the Junk DNA Concept on Scientific Advance
- “Does the Evolutionary Paradigm Stymie Scientific Advance?” by Fazale Rana (article)
- “Evolution’s Flawed Approach to Science” by Fazale Rana (article)
- “Does Evolutionary Bias Create Unhealthy Stereotypes about Pseudogenes?” by Fazale Rana (article)
- John A. Frank et al., “Evolution and Antiviral Activity of a Human Protein of Retroviral Origin,” Science 378 (October 28, 2022): 422–28, doi:10.1126/science.abq7871.
- Edward J. Grow et al., “Intrinsic Retroviral Reactivation in Human Preimplantation Embryos and Pluripotent Cells,” Nature 522 (June 11, 2015): 221–25; doi:10.1038/nature14308.
- Francis S. Collins, The Language of God: A Scientist Presents Evidence for Belief (New York: Free Press, 2006), 111.
- Frank et al., “Evolution and Antiviral Activity.”