What is "alternate RNA decoding"?

I recently came across a paper in Nature on alternate RNA decoding. It looked interesting so I read the abstract. That didn't help. I was still confused about what the authors were assaying and whether it was anything other than translation or splicing errors. So I read the introduction to try and get a better understanding of alternate RNA decoding.

That didn't help. The rest of the paper wasn't any more helpful.

I'm going to reproduce the abstract and the relevant part of the introduction so you can judge for yourself whether I'm just being stupid or whether the authors should have been more clear about what they are doing. I think I'm reasonably well-informed about basic biochemistry and molecular biology principles and concepts but maybe I'm falling behind in my old age.

Nature is a prestigious journal and in the past (25 years ago) you could assume that any paper published in Nature was probably important. Today, I'm not so sure about that but maybe I'm being too critical.

"Eclipsed Horizons: Unveiling the Dark Genome" challenges the model of junk DNA

Eclipsed Horizons: Unveiling the Darfk Genome is a book by Sudhakaran Prabakaran that promotes the idea of a dark genome and challenges the concept of a genome that's mostly junk DNA. It was published by World Scientific in March 2026. The book costs about $90 (USD) so I'm not going to buy it even though the subject is of great interest to me. I just don't think it's going to be very good after reading the promotional blurb.

Eclipsed Horizons: Unveiling the Dark Genome presents a revolutionary perspective on the human genome, building upon years of research challenging the conventional notion that non-coding DNA is merely "junk." Through rigorous scientific analysis, this book advances a groundbreaking new theory: that these vast non-coding regions — comprising 98% of our genome — function as a sophisticated adaptive reservoir with latent potential that activates in response to environmental challenges.

Dr Prabakaran develops a compelling information-theoretic framework to understand how this "dark genome" operates as nature's supreme adaptive system. Beginning with a speculative scenario of space-adapted humans called Homo minimus, he traces the cosmic origins of life's elements, explores DNA's remarkable information architecture, and examines evolutionary transitions where non-coding regions played crucial roles in developing biological complexity. While incorporating speculative elements to engage readers, this text maintains academic rigor throughout, making it suitable as a textbook on the dark genome. Each chapter builds on empirical research while proposing testable hypotheses about stress-responsive elements of genomic function, regulatory networks, and the dark proteome that activate during environmental crises.

The culminating chapters explore potential implications for humanity's cosmic future, suggesting that the dark genome may harbor adaptations relevant to space environments. This hybrid approach — balancing academic precision with accessible narrative and thoughtful speculation — makes the book valuable for both specialized academic audiences and interested general readers seeking a deeper understanding of genomic complexity beyond conventional paradigms.

Has anybody read this book? Please let me know if Prabakaran is making any good arguments that haven't already been refuted years ago. Does he reference my book?

---

Tofino Airport: 1942 and 2026

We visited Tofino on the west coast of Vancouver Island (British Columbia, Canada). We took a seaplane from Vanvouver harbor to the harbor in the town of Tofino. On the return trip we passed over the Tofino-Long Beach Airport (YAZ) located a few kilometers south of Tofino and we got a good photo of it from the air.

The airfield was constructed in 1942, shortly after Canada declared war on Japan. [RCAF Station Tofino]. It's purpose was to protect the west coast from Japanese submarines that were harassing merchant ships in the Eastern Pacific.

My father was Laurence Victor "Vic" Kirsch.¹ He got his wings in April 1942 and joined RCAF 132 Squadron. They were first stationed at Sea Island (now Vancouver International Airport (YVR)) then transferred to Patricia Bay (Pat Bay, now Victoria International Airport (YYJ)). On Oct. 15th the squadron landed at Tofino.

Intelligent Design Creationists are still spreading lies about junk DNA

Intelligent Design Creationists have convinced themselves that there's no junk DNA in the human genome. They predicted this more than 30 years ago based on the idea that their god(s) would never have designed humans with a genome full of junk DNA. They firmly believe that modern science has shown them to have been correct.

The ID creationists are in the midst of congratulating themselves on their successes while celebrating the 30th anniversary of the publication of Darwin's Black Box. Most of the posts on the Science & Culture Today website are laughable and I stopped responding to them several years ago. However, I think it's worthwhile to highlight one of Casey Luskin's posts to show you just how ignorant they are about real science. [Thirty Years of Intelligent Design Predicting the Unexpected Genome]

The evolution of metabolic enzymes in LUCA, Bacteria, and Archaea

The best scenario for the origin of life is that it first arose in hydrothermal vents deep in the ocean. The first catalysts of metabolic reactions were metals and later on simple organic molecules bound to metals. The substrates for all reactions were inorganic compounds such as H₂, CO₂, NH₃, H₂S and phosphate/phosphite.

Over time, the inorganic catalysts were gradually replaced by protein and RNA catalysts that often incorporated the metal ions into their active sites or used cofactors containing metal ions. There are about 400 basic metabolic reactions that are fundamental to life. Some enzyme catalysts are very ancient but others seem to be more recent.

Do scientists at Amgen understand the human genome?

Amgen Inc. is a major pharmaceutical company based in Thousand Oaks, California (USA). [Wikipedia: Amgen] It was founded in 1980 to exploit developments in biotechnology, especially recombinant DNA technology. (Amgen is short for Applied Molecular Genetics.)

Like most pharmaceutical companies, Amgen produces promotional videos that are supposed to show how close they are to cutting edge science. Here's one that celebrates DNA Day and answers the question "What Is the Dark Genome? 98% of DNA explained." Are you impressed?

What Is the Dark Genome?

---

Anaerobic carbon fixation in ancient prokaryotes

Most of us were taught that plants are the main source of fixing carbon from carbon dioxide. Some of us even had to memorize the enzymes and reactions of the Calvin Cycle including the complicated reaction catalyzed by rubisco, the main CO₂ fixing enzyme. [Fixing Carbon: the Rubisco Reaction].

We were led to believe that plants were the main source of sugars and other organic molecules but that's because undergraduate biochemistry education emphasizes human biochemistry. Photosynthesis and plants are only important because they are food. We were also taught, incorrectly, that photosynthesis is defined as a carbon-fixation process. [What is photosynthesis?]

It turns out that the Calvin Cycle isn't restricted to plants and it doesn't even require oxygen. Anaerobic bacteria also have a version of the Calvin Cycle and they are perfectly capable of fixing carbon without a major energy source like photosynthesis. [Carbon Dioxide Fixation in the Dark Ocean]

This makes sense since the earliest forms of life had to be able to turn inorganic molecules (e.g. CO₂) into organic molecules so they had to be able to fix carbon. Current models of the origin of life are referred to as Metabolism First models because they postulate that life began with simple metabolic reactions that made organic molecules from inorganic molecules. One of the most important of these early reactions is the fixation of two molecules of CO₂ into a two carbon compound (acetate).

The functions of human protein-coding genes

There are about 20,000 protein-coding genes in the human genome. We'd like to know what all these genes are doing but the only way to find out is to rely on experiments that explore the function of an individual protein.

This functional data has been collected and assembled in a large database called the Gene Ontology Resource (GO). Unfortunately, it only covers about one third of all human proteins.

Feuermann et al. (2025) developed a program to extend the coverage provided by direct annotation of human genes by making use of annotation records in related genes from other species. They constructed phylogenetic trees for 6,333 gene families representing a total of 17,079 human genes. This allowed them to deduce the functions of many more genes by taking advantage of GO annotations in homologous genes.

The "Venn diagram" (their words) illustrates the advantage of combining phylogenetic data with GO annotation. The yellow part represent the fraction of human proteins that have been directly annotated in the GO database while the brown and blue sections show how function can be inferred from a much larger set of proteins by looking at annotations in other species.

The results are not surprising. Most of the proteins are involved in basic metabolism such as cellular processes: (deep blue), cellular metabolism: (blue), and cell structure (cell structure: dark blue). Most of the genes families involved in these functions are derived from single genes that are also found in bacteria. The important point here is that the increase in number of genes in complex eukaryotes is mostly due to gene duplication and subspecialization.

---

Feuermann, M., Mi, H., Gaudet, P., Muruganujan, A., Lewis, S.E., Ebert, D., Mushayahama, T., Consortium, G.O. and Thomas, P.D. (2025) A compendium of human gene functions derived from evolutionary modelling. Nature 640:146-154. [doi: 10.1038/s41586-025-08592-0]

Why do scientists at "elite" universities dominate scientific discourse?

We all know that scientists at elite universities publish a lot more papers than scientists at other universities. Why is that? Is it because those universities have better labs and equipment? Is it because the scientists at elite universities are smarter than other scientists? Is it because of the reputation of the universities that makes it easier to get papers accepted in the best journals?

A group of scientists at the University of Colorado (Boulder, Colorado, USA) decided to examine the question and they came up with another answer—one that I have long suspected.

Pervasive transcription = genes + noise

Most of the DNA in the human genome is transcribed at some point in development or in some cell type. This fact has been known since the late 1960s.

There are basically two types of transcripts. Functional transcripts mostly come from genes although there might be a few exceptions (e.g. enhancer RNAs). Non-functional transcripts can be produced by pseudogenes or from virus and transposon fossils. They can also due to transcriptional noise caused by spurious transcription.

Philosophers talk about junk DNA

There is considerable debate in the scientific literature over the amount of junk DNA in the human genome. The standard model was developed 50 years ago; it postulated that only 10% of the genome is functional and 90% is junk. Most of the evidence since then has supported that model but there are many scientists who reject it.

This would seem to be fertile ground for philosophers of biology and, indeed, there are some philosophers who have made a significant contribution, mostly in sorting out how to define function (Brunet et al., 2021; Linquist et al., 2020). Also, many philosophers are interested in the history of biology and some (e.g. Morange, 2020) have done a good job of describing the history of the junk DNA concept.

Ask Gemini: "What is the difference between junk DNA and non-coding DNA?"

This is weird. I was a bit bored so I asked Gemini the following question: "What is the difference between junk DNA and non-coding DNA?" I thought the first answer was so wrong that I decided to ask it again to see if I got the same answer.

The second answer was quite different because Gemini noticed that I had bookmarked Sandwalk, a blog written by Laurence Moran, a champion of the 'junk DNA' concept. Is it trying to give me the answer it thinks I want or the best possible scientific answer?

Note: Here is the correct answer.

Non-coding DNA refers to the part of the genome that doesn't code for proteins. It's one way to partition the genome - you could also refer to regulatory sequences and non-regulatory sequences.

By the late 1960s scientists knew of lots of functional non-coding DNA such as regulatory sequences and non-coding genes such as those for ribosomal RNA and tRNA. (There are other non-coding functional elements.) It became apparent that most of the human genome consisted of non-functional DNA or junk DNA. The original model back then was that 10% is functional and 90% is junk. The 10% that is functional consisted of 1-2% coding DNA and about 8% of functional non-coding DNA.

No knowledgeable scientist ever said that all non-coding DNA was junk; that's a lie that continues to be perpetuated in scientific publications and the popular media even though it has been repeatedly debunked.

Most of the data that has accumulated over the past 50+ years has supported the idea that 90% of the human genome is junk and only 10% is functional.

The Gemini answers relate to the debate concerning whether AI is really intelligent and, more importantly, whether the popular (free) algorithms are spreading misinformation.

How many pseudogenes in the human genome?

There are somewhat less than 25,000 genes in the human genome and there are probably about the same number of pseudogenes.

Pseudogenes are sequences that resemble real functional genes but they contain mutations that render them non-functional. They are very real examples of junk DNA.

There are four kinds of pseudogenes. Duplicated pseudogenes arise from a gene duplication event when one of the original copies mutates. Duplicated pseudogenes retain all of the features of the original gene, including introns and adjacent regulatory sequences. The inactivating mutation may occur in the gene itself—for example in the coding region of a protein coding gene—in which case the pseudogene may still be transcribed. Duplicated pseudogenes are usually found adjacent to their parent gene.

Processed pseudogenes arise when the normal transcript is copied by reverse transcriptase and the DNA copy is reintegrated into the genome. Processed pseudogenes don't have introns or regulatory sequences and they are not near their parent gene. Most processed pseudogenes come from transcripts that are expressed in the germ line.

Suggestions for philosophers who want to contribute to philosophical biology

Can modern biologists get along with modern philosphers of biology? James DiFrisco and Steven Orzack think they can and they have suggestions for both biologists and philosophers (DiFrisco and Orzack, 2026).

Here are their suggestions for philosophers who want to contribute to philosophy of biology.

1. Justify engagement with philosophical biology by its capacity to improve biology. Do not justify engagement with a topic by pointing to its interest to philosophers, or by a generic appeal to interdisciplinarity, or by apparent thematic overlap.
2. Understand that conceptual analysis needs to make a difference to scientific reasoning and practice. The development and clarification of biological concepts is best when based upon actual biology as opposed to imaginary counterfactual scenarios and thought experiments.
3. Attain at least the level of comprehension of biology possessed by a senior undergraduate major in biology.
4. Publish normative claims about biology in biology journals, not just in philosophy journals.
5. Attend and present work at biology conferences. Collaborate with biologists.
6. Ensure that articles or books about a philosophical issue in biology are reviewed by a biologist with relevant expertise.
7. Do not claim what author X means (without documentation), as in “what Smith really means here is ….” Accept potential ambiguity as a part of human communication.
8. Anchor a descriptive claim about biology in the actual practice of biology. Engage with current biology and not just biological authorities from the past (e.g., Darwin).
9. Understand that claims by biologists need to be understood in their social and historical context in addition to their epistemic context.

---

DiFrisco, J. and Orzack, S.H. (2026) Biology Needs Philosophy, But What Philosophy? BioScience:biag016. [doi: 10.1093/biosci/biag016]

Suggestions for biologists who want to contribute to philosophical biology

Can modern biologists get along with modern philosphers of biology? James DiFrisco and Steven Orzack think they can and they have suggestions for both biologists and philosophers (DiFrisco and Orzack, 2026).

Here are their suggestions for biologists who want to contribute to philosophy of biology.

1. Understand that debate over definitions is often not quibbling over “mere” semantics. After all, semantics concerns meaning, and meaning connects concepts to inferential roles in reasoning, including prediction.
2. Understand that concepts having an uncertain connection with facts may still be useful. For example, the notion of a species as an ensemble of potentially interbreeding individuals has underwritten many important empirical insights into evolution, even though it can be hard to measure the potential for interbreeding over time and space. Similarly, the notion of an organ as a well-defined ensemble of cells has underwritten many important empirical insights in anatomy, pathology, and physiology even though the criteria that define organs remain in dispute.
3. Understand that there can be useful theory in biology even if it is not expressible in compact mathematical form.
4. Understand that theory can be important apart from its immediate empirical usefulness. However, theory that is informed by data and that informs data is most useful.
5. Understand that explanations of phenomena do not have to be molecular in order to be causal and mechanistic. The limits of explanations based upon molecular mechanisms do not necessitate switching to a different mode of explanation (e.g., one based on agency; see below).
6. Take guidance from philosophy when making philosophical claims. Debates by philosophers over issues such as falsifiability as a defining criterion of science; the uses of abduction, deduction, and induction; essentialism in classification; and the nature of scientific laws can improve scientific practice.

---

DiFrisco, J. and Orzack, S.H. (2026) Biology Needs Philosophy, But What Philosophy? BioScience:biag016. [doi: 10.1093/biosci/biag016]