A watercolor painting depicts chimeric mRNAs.
Image: Hannah Davis/Jackson Lab.
An immune system that saves your life in one circumstance can help kill you in another makes sense in the light of evolution: natural selection favours advantages whose benefits outweigh their costs under prevailing conditions, without guaranteeing safety in every eventuality. For creationists who present biological complexity as evidence of perfect intelligent design, however, such compromises require some explaining.
A new study published in Nature on 2 September 2026 provides a particularly revealing example. Researchers found that mammalian cells can join RNA sequences copied from separate genes into a combined message. One resulting protein improves antibacterial defence in mice, but also increases vulnerability to lethal inflammatory responses in experimental models of sepsis. The same molecular mechanism brings both protection and danger.
To understand the discovery, think of DNA as a collection of stored recipes. Messenger RNA, or mRNA, is a working copy that a cell uses to assemble a protein. Scientists have long known that cells can edit these copies, allowing a single gene to produce different proteins. Here, the researchers investigated messages containing material from different genes, sometimes located on different chromosomes. It is rather like making a new recipe by combining instructions from two separate cookbooks. The joining occurs at the RNA level; it does not require the original DNA recipes to merge.
These combined messages are called chimeric RNAs. Crucially, the team demonstrated that one produces a functional protein, named GSDMD–TMEM106A, during inflammation in mice. Most of the other candidate messages have yet to be shown to produce functional proteins, so the discovery should not be mistaken for proof that every detected combination has a useful role.
The evolutionary interest lies in the consequences. Strengthening an inflammatory response can help an animal resist infection, yet the resulting damage can become lethal. Weakening that response can reduce the danger from inflammation while leaving the animal less able to control bacteria. There is no simple setting at which “more immunity” always means “better health”.
This is precisely the sort of trade-off evolutionary biology helps us understand. Natural selection works with inherited mechanisms and their competing consequences; it has neither foresight nor a commitment to the welfare of every individual or to the perfect solution. The study does not reconstruct the evolutionary history of this particular protein, but its findings illustrate why a useful biological feature need not be harmless, let alone perfect. For intelligent-design advocates, the question is therefore more demanding than “Is it complicated?” It is why an allegedly flawless designer’s protective machinery comes with the capacity to inflict fatal damage on the organism it protects.
Why Evolution Produces Compromises. Why are living things so often less than perfectly adapted? Why do bodies have weaknesses, why can useful genes also cause problems, and why can an immune system become dangerous to the animal it protects? The answer is that evolution does not work towards a planned, perfect outcome. Natural selection favours inherited variations that improve reproductive success in particular circumstances, subject to several unavoidable constraints.The paper in Nature is accompanied by a news item from Havard Medical School:
- Natural selection works with what is available
Evolution modifies structures and processes inherited from ancestors. Mutations introduce variation, and recombination reshuffles existing genetic material, but neither supplies whatever an organism happens to need. An advantageous change can spread only if it arises, and its route to becoming established depends on its effects in the organisms that actually carry it.
Consequently, evolution cannot simply scrap an awkward arrangement and start again. Major changes generally have to proceed through intermediate forms capable of surviving and reproducing.- Benefits often come with costs
A feature can improve one aspect of an organism’s performance while worsening another. Stronger immune responses can help control infection but also damage healthy tissues. More investment in reproduction can leave fewer resources for maintenance and repair. A thicker protective shell may provide better defence while requiring more energy to build and carry.
These are evolutionary trade-offs. A feature can be favoured when its reproductive benefits outweigh its costs, even if those costs include disease or an increased risk of death in some circumstances.- “Best” depends on the circumstances
An adaptation is useful in a particular environment. Conditions change, including climate, food availability, predators and pathogens. A characteristic that was advantageous in one setting may become a liability in another. Different environments can also favour different versions of the same trait.
There is therefore no single, permanently ideal organism towards which evolution is progressing.- Selection has no foresight
Natural selection cannot favour a disadvantageous change because it might enable something useful many generations later. Nor does it plan for future environmental changes. It reflects differences in survival and reproduction under the conditions organisms encounter.
Its consequences also need not maximise lifespan, comfort or health. A trait that improves reproductive success can spread despite harmful effects later in life, when selection against those effects is often weaker.- Not every evolutionary change is an improvement
Chance also changes populations. Through genetic drift, genetic variants can become more or less common irrespective of their usefulness, especially in small populations. Slightly harmful variants can sometimes become established, while beneficial ones can disappear. Evolution includes natural selection, but it is not governed by selection alone.
The example in this study
In the mouse experiments, the chimeric protein GSDMD–TMEM106A strengthened antibacterial defence but increased susceptibility to lethal sepsis in experimental models. Removing it reduced the danger from sepsis while compromising resistance to bacteria. This demonstrates a biological trade-off; it does not, by itself, establish exactly how natural selection shaped the protein’s history.
Calling such outcomes “sub-optimal” requires one qualification: an evolved compromise can perform very well under its usual conditions without being best at every task or safe in every circumstance. Evolution does not literally “settle” for anything. It has no intentions, no blueprint and no final goal.
These distinctions matter when assessing creationist claims that biological complexity implies intelligent design.
How understanding evolution and biological systems comprehensively refutes creationism is explained in Rosa Rubicondior, 20 Reasons To Reject Creationism: Understanding Evolution.
Mammalian Genes Can Combine To Make Previously Unknown mRNAs, Proteins
At a glance
- Researchers have discovered that mammalian genes can combine to make chimeric mRNAs, which carry the instructions to produce previously unknown, functional proteins.
- The first chimeric mRNA they investigated, in mice, has an important role in modulating inflammatory responses.
- Findings expand understanding of biology, genome and add potentially thousands of new targets for drug discovery.
For decades, scientists have understood that each of the roughly 20,000 genes in the human body carries the instructions for a single kind of protein. Now, researchers at Harvard Medical School have discovered that instructions from different genes — even those on different chromosomes — can combine to create chimeric mRNAs that produce previously unknown, functional proteins.
The findings, published Sept. 2 in Nature, reveal the existence of potentially thousands of new chimeric proteins and demonstrate that at least some of these play important roles throughout the body.
Nobody knows these exist. Medicine doesn’t know they exist, the pharmaceutical industry doesn’t know they exist. We’ve discovered an entirely new gene regulation system that could expand the known genome and proteome dramatically.
Assistant Professor Ruaidhrí Jackson, senior author
Department of Immunology
Harvard Medical School
Boston, MA, USA.
While the researchers don’t yet know how widespread the phenomenon is, chimeric proteins could be involved in a variety of systems and may contribute to disease processes that are poorly understood at the moment. This overlooked aspect of biology could offer new insights into challenging diseases and provide a new avenue for finding drug targets to treat them.
There are suddenly many new possibilities for the kind of molecules and proteins that cells can create. If it is possible to leverage chimeric RNAs for drug discovery and medicine, then this is very exciting.
Harry Kane, co-first author.
Department of Immunology
Harvard Medical School
Boston, MA, USA.
A “dark genome” library
While some single-celled and invertebrate organisms, such as trypanosomes and nematodes, can combine genes for regulatory purposes, these systems don’t seem to create proteins and have not been found in mammals. The best-known examples of chimeric mRNA in humans came from cancer-causing abnormalities where DNA breaks into pieces and some of the scattered genes fuse together.
RNA sequencing results occasionally suggested that chimeric mRNA could exist in healthy tissue, but traditional sequencing techniques had difficulty finding them and may have even created some artificially.
This project was high risk, high reward from the very beginning. We didn’t know how many chimeric mRNAs we would find or if they would be biologically relevant.
Olivia Venezia, co-first author.
Department of Immunology
Harvard Medical School
Boston, MA, USA.
Using a new technology called direct RNA sequencing, the researchers were able to compile a list of over 30,000 chimeric mRNAs that have been observed at least once in mammalian cells — the “dark genome” library, Jackson calls it. So far, they have been able to profile how almost 400 of these are regulated by inflammatory signals, including chimeric mRNAs conserved in both human and mouse immune cells.
The team found that healthy chromosomes can loop together in mouse cells as part of the immune response, bringing the normally distant genes into proximity. The newly adjacent genes transcribe a chimeric mRNA, which takes part of its sequence from each gene and produces a protein that is a hybrid of the two.
We thought we had a blueprint of every mRNA that is made in the body, and now we’re saying that was just page one. There are all these other combinations that can occur.
Assistant Professor Ruaidhrí Jackson.
But the existence of chimeric mRNA doesn’t necessarily mean that it creates functional proteins or plays a significant role in the body.
A functional chimera
To determine whether a chimeric mRNA could actually serve a biological purpose in mammals, Jackson and his team chose to investigate one they found in mice: a combination of the genes encoding GSDMD and TMEM106A. The protein created by GSDMD alone is responsible for opening up cell membranes during pyroptosis, a process in which immune cells burst open to summon a large inflammatory response.
First, the team confirmed that the chimeric protein, GSDMD-TMEM106A, occurred naturally in mice. Indeed, it was produced as part of the immune response in cells from two different strains of lab mice as well as a wild-derived strain.
Then the researchers developed a genetic tool to stop the production of the chimeric protein without interfering with the production and function of the standard GSDMD and TMEM106A proteins.
They found that mice without the chimeric protein had a slower immune response than normal mice. When the mice were infected with Salmonella, they were less able to fight off the bacteria.
They can’t control the bacterial infection. Nearly 50 percent of the immune process has been reduced without our chimeric protein, even though the normal GSDMD is still present. GSDMD needs our GSDMD-TMEM106A to function fully.
Assistant Professor Ruaidhrí Jackson.
The researchers also tested the mice with an endotoxin that causes sepsis — an extreme immune response that can be deadly. Seventy percent of mice without the chimeric protein survived and recovered from what would normally be a lethal dose, because their immune response was milder than normal.
The researchers worked with the biotechnology company Moderna to engineer an mRNA that would boost the production of GSDMD-TMEM106A in the mice. Mice with elevated levels of the chimera did not survive even a mild endotoxin dose.
However, mice that lacked the GSDMD gene and also had elevated levels of the chimera (courtesy of the engineered mRNA) had no response to the endotoxin at all. This demonstrated that while GSDMD-TMEM106A significantly speeds up the process of pyroptosis, it cannot open the cell membranes without GSDMD.
The findings confirmed that this chimeric protein is vital for the inflammatory response in mice.
GSDMD-TMEM106A was initially discovered based on a single read in one of our samples. We were bracing ourselves for this to turn out to be nothing. It was very exciting when we found that GSDMD-TMEM106A was not only a real protein but also functional — it could modulate release of inflammatory molecules from cells.
Harry Kane.
Exploring the potential of chimeric RNA
There is still a lot to learn about chimeric mRNA. Jackson, Kane, Venezia and their colleagues are continuing to explore the molecular cues behind its formation — why the two partial gene sequences are always connected at the same point, why chimeric proteins take certain shapes, and what triggers the chromosomes to bring specific genes together.
But they are most excited about evaluating a variety of chimeric mRNAs for potential uses in medicine.
We want to find out which ones are operative in currently incurable diseases. We think we can find new players that have been completely overlooked by medicine, by pharma, by biomedical science in general.
Assistant Professor Ruaidhrí Jackson.
The Jackson Lab is currently investigating several chimeric mRNAs that could be involved in cancer, inflammatory disease, and neurodegenerative disease. They have shared additional chimeric mRNA sequences with colleagues interested in a variety of other processes.
It will take years of research and effort from many different scientists to figure out the best ways to study chimeric RNAs and characterize their biological relevance. If this pattern turns out to be widespread and lots of chimeric RNA molecules are doing interesting things in cells, this opens up a ton of possibilities for discovering new biology and finding new targets for drug discovery.
Harry Kane.The future of federally funded research at Harvard Medical School — supported by taxpayers and done in service to humanity — remains uncertain. Learn more.Publication:
What makes this discovery particularly interesting is that a cell’s functional repertoire extends beyond a simple inventory of individual genes. By joining RNA copied from separate genes, cells can produce a functional protein whose complete instructions do not occur together at a single location in the DNA. Existing sequences can therefore contribute to additional biological functionality through a different arrangement. The researchers demonstrate this in their study of the mouse protein GSDMD–TMEM106A, although the functions of most other candidate chimeric messages remain unestablished.
This undermines the creationist assumption that every new function requires an independently supplied set of genetic instructions. Evolution can modify, duplicate and recombine what already exists; this research reveals another way in which the expression of existing sequences can expand what cells produce. Whether creationists choose to call the resulting combination “new information” is a matter of terminology. The biological mechanism requires no magical intervention.
There is an important distinction, however, between an evolutionary origin without foresight and an entirely random process operating in cells today. Natural selection can preserve and refine useful effects arising from initially incidental variations, eventually producing regulated mechanisms. That is a plausible route for the evolution of such systems, but this paper does not establish that particular history. The reserchers found that many chimeric mRNAs have no known function. Although this doesn't establish that they are useless, it hardly equates to the work of an intelligent designer, unless it lacks foresight and it's modus operandum is to create lots of random variations to see if any will work.
But the demonstrated trade-off is problem enough for creationists. In mice, the protein improves antibacterial defence while increasing the danger from lethal inflammation in experimental sepsis. Its usefulness comes with a cost. That is entirely consistent with evolution preserving advantages under particular conditions without guaranteeing safety in every circumstance. For advocates of a perfect, benevolent designer, the challenge is to explain why protection should carry this potentially fatal liability. Complexity alone does not answer that question.
Advertisement
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
Amazon
All titles available in paperback, hardcover, ebook for Kindle and audio format.
Prices correct at time of publication. for current prices.
No comments :
Post a Comment
Obscene, threatening or obnoxious messages, preaching, abuse and spam will be removed, as will anything by known Internet trolls and stalkers, by known sock-puppet accounts and anything not connected with the post,
A claim made without evidence can be dismissed without evidence. Remember: your opinion is not an established fact unless corroborated.