There have been dozens of studies on the possible harmful effects of glyphosate. There are many well-funded organizations and tons of lawyers who would like nothing better than to sue Monsanto/Bayer into bankruptcy for promoting Roundup® and there are many environmental and health organizations who claim that glyphosate is harmful to humans.
The claims that glyphosate causes cancer and other ill effects in humans fall into three main categories.
I'll follow up with links to all the articles showing that glyphosate is safe for humans. This is important because there's a lot of misinformation out there and the news media are not doing a very good job of countering the hype against glyphosate by presenting the consensus views of the scientific community. It's time for scientists to push back and make sure the the media are doing the job they're supposed to do; informing the public.
Glyphosate is a relatively simple chemical called N-(phosphonomethyl) glycine. It is a potent inhibitor of one of the key enzymes in the pathway for synthesis of the aromatic amino acids, tryptophan, phenylalanine, and tyrosine [How Cells Make Tryptophan, Phenyalanine, and Tyrosine].
Specifically, the herbicide blocks the activity of EPSP synthase, the enzyme that catalyzes one of the steps leading to chorismate. Chorismate is the precursor of all three aromatic amino acids so by blocking this enzyme, the synthesis of three plant amino acids is prevented.
Plants need to synthesize all 20 amino acids so this blockage causes plants to die.
The glyphosate mechanism is well known from studies of the homologous bacterial versions of EPSP synthase. An example of glyphosate bound to the active site of the E. coli enzyme is shown on the right. When glyphosate is bound, the enzyme can't catalyze any reaction.
Animals have lost the ability to synthesize chorismate and the aromatic amino acids so they require tryptophan, phenyalanine, and tyrosine in their diet. What this means is that the potent herbicide, glyphosate, has no effect on animals since they have already dispensed with the EPSP synthase enzyme. That's one of the reasons why Roundup® is so safe for humans.
Those of you who have used Roundup® on your driveways and walkways know that it kills all plants indiscriminately. You'd better not get it on your wife's favorite roses (... not that I'm admitting anything, mind you).
You can't spray it on crops, such as soybeans, corn, cotton, granola, and wheat to get rid of weeds because it kills the crops as well as the weeds. Wouldn't it be nice to have Roundup® resistant crops so you could spray them to control weeds?
Monsanto makes Roundup® and and they thought so too. That's why their scientists searched for, and found, bacteria that were resistant to Roundup®. Then they transferred the gene for the resistant EPSP enzyme to various crop plants in order to make them resistant to Roundup®. [Roundup Ready® Transgenic Plants]
These Roundup Ready® crops are now found everywhere in Canada and the United States. Farmers routinely spray these crops with Roundup® in order to kill all the weeds in a field while saving the crop.
Since these farmers are handling tons of Roundup® every year, they would make a good group to examine for any adverse health effects, don't you think?
I've been reading Mathew Cobb's biography of Francis Crick and a sentence in the Prologue caught my eye.
Cricks' scientific writings and ideas are described in a way that should be easy for the general reader to understand, but if you find yourself struggling, follow Crick's advice to readers of his own books and skip the hard bits.
I meet regularly with a group of retired professors to discuss a wide range of topics. Yesterday we talked about misinformation and how to deal with it but the discussion brought out the differences between dealing with misinformation in the humanities and in medicine or the natural sciences. This led to a diversion that focused on The Two Cultures.
We may not know a lot about how artificial intelligence (AI) algorithms work but the one thing we do know is that they are only as good as their databases. If you ask an AI program to tell you when Charles Darwin was born then chances are good it's going to give you the correct answer because that information is in Wikipedia and lots of other reliable online sources.
However, if you ask it to tell you how many genes are in the human genome it will not give you the correct answer. The correct answer is that we don't know for sure because it depends on how you define a gene and how many non-coding genes there are using various definitions. That's not the answer you will get. (I personally believe that there are only about 1000 non-coding genes but I don't expect a good "intelligence" program to favor my view over others. I DO expect it to not favor other opinions over mine.)
I just asked ChatGPT and it told me that there are tens of thousands of non-coding genes based on the Human Genome Project plus GENCODE and Ensemble annotations. This is correct ... and misleading. It's giving the best answer it can based on the databases it searches. However, many of us are skeptical of the GENCODE and Ensemble annotations and for good reason. They tend to err on the side of inclusion in order to avoid false negatives. In other words, they don't want to risk ignoring a real biologically relevant feature for lack of evidence so they deliberately risk including a lot of false positives. This is why those databases include a lot of questionable features such as non-coding genes, multiple transcription start sites, multiple splice variants, and tons of potential regulatory elements.
Along comes AlphaGenome. It's an AI program designed to scan those GENCODE and Ensemble databases to identify important features that might play a role in genetic diseases. What could possibly go wrong? [How intelligent is artificial intelligence?] [Will AlphaGenome from Google DeepMind help us understand the human genome?]
The average science writer jumped all over the original announcement of AlphGenome to let us all know that artificial intelligence was going to solve the problem of the mysterious genome. Apparently the complexity of the human genome has astonished scientists ever since the first human genome sequence was published 25 years ago.1 The typical article on AlphaGenome fits nicely into the common theme that AI is soon going to rule the world.
That's why I was excited to pick up my copy of the New York Times yesterday and see that Carl Zimmer had written about AlphaGenome. Finally, an intelligent, highly respected, science writer was going to give us the truth. Here's the article that I saw in my version of the paper. (It was originally published several weeks ago on January 28, 2026.)
What a disappointment! Zimmer goes with the hype about AlphaGenome and repeats some of the tropes that he has avoided in the past. For example, he writes about how alternative splicing can create hundreds of different proteins from a single gene and how regulatory sequences can lie thousands or million of base pairs away from a gene. (There's no question that this is true for a small number of transcription factor binding sites but the vast majority are close to the promoter.)
I checked the online version of Carl Zimmer's article in order to prepare for this blog post. I was surprised to see that there were lots of things in the online version that weren't in the newspaper article. For example, Zimmer quotes my colleague Alex Palazzo saying that everybody uses AlphaFold to study proteins then later on in the article Zimmer notes that, "But the more scientists studied the human genome, the more complicated and messy it turned out to be." The newspaper article left out the words "and messy" and that's significant because junk DNA supporters like Alex Palazzo often refer to the human genome as "messy" and full of junk DNA and that's a very different perspective than opponents of junk DNA who emphasize things like "complicated" and "mysterious."2
Zimmer has an even more revealing section that's in the online version but not the newspaper version.
Peter Koo, a computational biologist at Cold Spring Harbor Laboratory in New York who was not involved in the project, said that AlphaGenome represented an important step forward in applying artificial intelligence to the genome. “It’s an engineering marvel,” he said.
But Dr. Koo and other outside experts cautioned that it represented just one step on a long road ahead. “This is not AlphaFold, and it’s not going to win the Nobel Prize,” said Mark Gerstein, a computational biologist at Yale.
AlphaGenome will be useful. Dr. Gerstein said that he would probably add it to his toolbox for exploring DNA, and others expect to follow suit. But not all scientists trust A.I. programs like AlphaGenome to help them understand the genome.
“I see no value in them at all right now,” said Steven Salzberg, a computational biologist at Johns Hopkins University. “I think there are a lot of smart people wasting their time.”
The end of the online article is quite different from the final paragraphs of the newspaper article. In the newspaper article, Zimmer describes the TAL1 result then ends it with the paragraph starting with "In reality." I've highlighted that paragraph in the quotations below from the online version.
The AlphaGenome researchers shared their TAL1 predictions with Dr. Marc Mansour, a hematologist at University College London who spent years uncovering the leukemia-driving mutations with lab experiments.
“It was quite mind-blowing,” Dr. Mansour said. “It really showed how powerful this is.”
But, Dr. Mansour noted, AlphaGenome’s predictive powers fade the farther its gaze strays from a particular gene. He is now using AlphaGenome in his cancer research but does not blindly accept its results.
“These prediction tools are still prediction tools,” he said. “We still need to go to the lab.”
Dr. Salzberg of Johns Hopkins is less sanguine about AlphaGenome, in part because he thinks its creators put too much trust in the data they trained it on. Scientists who study splice sites don’t agree on which sites are real and which are genetic mirages. As a result, they have created databases that contain different catalogs of splice sites.
“The community has been working for 25 years to try to figure out what are all the splice sites in the human genome, and we’re still not really there,” Dr. Salzberg said. “We don’t have an agreed-upon gold-standard set.”
Dr. Pollard also cautioned that AlphaGenome was a long way from being a tool that doctors could use to scan the genomes of patients for threats to their health. It predicts only the effects of a single mutation on one standard human genome.
In reality, any two people have millions of genetic differences in their DNA. Assessing the effects of all those variations throughout a patient’s body remains far beyond AlphaGenome’s industrial-strength power.
“It is a much, much harder problem — and yet that’s the problem we need to solve if we want to use a model like this for health care,” Dr. Pollard said.
The net effect of these differences is to transform the article from one that promotes AlphaGenome in the newspaper version to one that's far more skeptical in the online version. I believe that the online version is far more accurate and reflects the high standard that I expect from Carl Zimmer. I'm assuming that the newspaper article was edited for the New York Times supplement that I read and I'm assuming that Zimmer did not approve of that edit.
Note: The cartoon was generated by ChatGPT in response to the request, "draw a cartoon illustrating GIGO - garbage in garbage out."
Note: The photo is from 10 years ago when Carl was in Toronto working on his junk DNA article for The New York Times [Is Most of Our DNA Garbage?]. That's Alex Palazzo on the left, then me, Ryan Gregory, and Carl Zimmer on the right.
1. Most knowledgeable scientists were not astonished to learn that 90% of our genome really is junk and there are fewer than 30,000 genes.
2. See the last chapter of my book: "Chapter 11: Zen and the Art of Coping with a Sloppy Genome."
The amount of a given protein in Escherichia coli depends on a number of factors such as the amount of mRNA and the rate of translation. The standard model of regulation is based on decades of study of individual genes and it reveals that the amount of protein is mostly dependent on the amount of mRNA that was translated. This, in turn, indicates that most regulation occurs at the level of transcription initiation.
It's now possible to look simultaneously at the characteristics of large numbers of protein-coding genes to see whether this generality holds. That's what Balakrishan et al. (2022) reported in a Science paper a few years ago. They looked at the characteristics of 1900 protein-coding genes in E. coli to see how protein concentration was regulated.
We're interested in the last universal common ancestor of all life (LUCA). In theory, this is a species that gave rise to both Bacteria and Archaea. The general assumption is that this is a single species with a well-defined set of genes that can now be found in all, or almost all, living species.
There are some scientists who question that assumption because they see massive transfers of genes between "species" during the early history of life. This gives rise to a web of life and not a well-defined tree. [The Three Domain Hypothesis: RIP] [The Web of Life] If that model is correct, then the ancestor of all living species could be a group of species that contributed different genes to a pool of organisms that lived billions of years ago. Early Bacterial and Archaeal ancestors could have independently acquired some genes by horizontal gene transfer.
Over the past few years I've been assessing AI algorithms to see if they can answer difficult questions about junk DNA, alternative splicing, evolution, epigenetics and a number of other topics. As a general rule, these AI algorithms are good at searching the internet and returning a consensus view of what's out there. Unfortunately, the popular view on some of these topics is wrong and most AI algorithms are incapable of sorting the wheat from the chaff.
In most cases, they aren't even capable of recognizing that there's a controversy and that their preferred answer might not be correct. They are quite capable of getting their answer from known kooks and unreliable, non-scientific, websites, [The scary future of AI is revealed by how it deals with junk DNA].
Others have now recognized that there's a problem with AI so they devised a set of expert questions that have definitive, correct, answers but the answers cannot be retrieved by simple internet searches. The idea is to test whether AI algorithms are actually intelligent or just very fast search engines that can summarize the data they retrieve and create an intelligent-sounding output.
It seems reasonable to assume that there's a genetic component to aging and the human life span. For example, it's clear that if you inherit bad genes (alleles) from your parents then your chances of living a long life will be diminished. It's also clear that a lot of deaths (short life span) are not due to alleles you inherit from your parents but to extrinsic factors such as accident, war or disease. It's true that some diseases, such as cancer, have a heritable component but even people with "good genes" can die of cancer.
What's not clear is how much of the underlying, intrinsic, component of life span is due to alleles you inherit from your parents. If you look at the average life expectancy of men and women in different countries you can see that the average life expectancy of an American is about 80 years but people in Japan can expect to live five years longer. Is that difference due to genetics, or better health care, or something else?
New Scientist has produced a special issue on the best ideas of the 21st century. Here's the complete list.
The National Center for Science Education (NCSE, United States) is an organisaton devoted to defending evolution and climate change. It has a long and admirable history of defending evolution from creationist attacks and of keeping creationism out of American public schools. Part of that defense involves keeping religious teachers and scientists as allies by suppporting the view that there is no necessary conflict between religion and science. NCSE has been a strong supporter of methodological naturalism—the view that science is restricted to investigating the natural world. I'll refer to this view as accommodationism.
American Secretary of State Marco Rubio thinks that the United States of America has been subsidizing the defense of Europe and it's time for European nations (and Canada) to start paying more to defend Europe against Russia. According to Rubio, the other NATO countries have been taking advantage of the United States by cutting back on defense spending and using the money to fund social programs. (Gasp!)
Yeah, but our like-minded partners have to have capability and that's been part of the problem is the erosion in European defense capabilities because they've taken vast amount of the monies that these are rich countries and because of the NATO umbrella they it gave them the flexibility to spend a tremendous amount of their revenues on social programs and not on defense. Now maybe that trend line will begin to change.
First, let's be very clear about the huge US military budget. Only a fraction of that money is being used in the direct defense of Europe from Russian aggression. Canada, Poland, and France do not need to spend billions on B2 bombers that spend most of their time sitting on airfields and only occasionally are used to bomb targets in Iran. They do not need to spend billions on nuclear powered aircraft carriers positioned in the Caribbean or the South China Sea. They do not need to pay for troops in Iraq and Syria. They do not need to give Israel almost four billion dollars a year in military aid. And they do not need to spend huge amounts of money to fund a National Guard that can be used to police their cities.
Second, the Russian invasion of Ukraine has shown us that the threat from Russia is not that serious. Russia can't even conquer a medium-sized country right on its border. (Although it can do a lot of serious damage.) The idea that Russia poses a serious military threat to the main NATO countries is ludicrous.
Third, for all its posturing about defending Europe, the United States has failed to provide Ukraine with the supplies and equipment needed to prevent a gradual Russian takeover of Ukrainian territory. I guess the Americans decided to use the money to fund social programs instead.
Fourth, Canada and the European NATO countries are pretty much done with the constant bullying and insults from American leaders. We may be on the verge of finding out whether the United States needs allies.
I was watching Marco Rubio testify before a Congressional committee this morning. I'm interested because I live in Canada and we are one of the countries in the Western Hemisphere that are now supposed to be under the thumb of the United States.
So I paid attention when Rubio explained how the protection racket works with Venezuela because Canada will soon be next on the list. I'll quote directly form his testimony below but here's how I think it works.
America is using its military power to blockade Venezuelan ports and prevent any oil from being shipped except under special circumstances. The sale of oil to foreign countries must be approved by the United States and the United States will determine the price—usually the current market price. The payment won't go to Venezuela, instead it will be deposited into special accounts, for example in Qatar, that will be controlled by members of the Trump administration.
Venezuela can apply to use this money but only for the benefit of the Venezuelan people. For example, Venezuela could use it to fund the police or purchase medicine and equipment from the United States. They can also use it to buy light crude oil that can be used to dilute their heavy crude. They used to buy this from Russia but now they are buying it all from the United States.
Members of the Trump administration will decide which projects to fund. Unused money from the sale of Venezuelan oil might become the property of the USA (or its leaders).
Marc Rubio forgot to mention the legal and ethical justification of such a scheme but I'm sure he'll explain it later on. Other countries in the Western Hemisphere are interested.
From The United States Department of State.
And one of the tools that’s available to us is the fact that we have sanctions on oil. There is oil that is sanctioned that cannot move from Venezuela because of our quarantine. And so what we did is we entered into an arrangement with them, and the arrangement is this. On the oil that is sanctioned and quarantined, we will allow you to move it to market. We will allow you to move it to market at market prices – not at the discount China was getting. In return, the funds from that will be deposited into an account that we will have oversight over, and you will spend that money for the benefit of the Venezuelan people.
Why was that important? Venezuela was running out of storage capacity, okay. They were producing oil. They were drilling oil. They had nowhere to put it. They had nowhere to move it. And they were facing a fiscal crunch; they needed money in the immediacy to fund the police officer, the sanitation workers, the daily operations of government.
And so we’ve been able to create a short-term mechanism. This is not going to be the permanent mechanism, but this is a short-term mechanism in which the needs of the Venezuelan people can be met through a process that we’ve created, where they will submit every month a budget of this is what we need funded. We will provide for them at the front end what that money cannot be used for. And they have been very cooperative in this regard. In fact, they have pledged to use a substantial amount of those funds to purchase medicine and equipment directly from the United States. In fact, one of the things they need is diluent*, or diluent* depending how you want to pronounce it. And that basically is the light crude that you need to mix with their heavy crude in order for the oil to be able to be mixed and moved. They’re getting – they used to get 100 percent of that from Russia. They are now getting 100 percent of that from the United States.
So we’re using that short-term mechanism both to stabilize the country but also to make sure that the oil proceeds that are currently being generated through the licenses we’ll now begin to issue on the sanctioned oil goes to the benefit of the Venezuelan people, not to fund the system that existed in the past.
The Third Way of Evolution is a strange organization composed of mavericks who think they're not getting enough attention. Here's how they describe their movement.
The vast majority of people believe that there are only two alternative ways to explain the origins of biological diversity. One way is Creationism that depends upon intervention by a divine Creator. That is clearly unscientific because it brings an arbitrary supernatural force into the evolution process. The commonly accepted alternative is Neo-Darwinism, which is clearly naturalistic science but ignores much contemporary molecular evidence and invokes a set of unsupported assumptions about the accidental nature of hereditary variation. Neo-Darwinism ignores important rapid evolutionary processes such as symbiogenesis, horizontal DNA transfer, action of mobile DNA and epigenetic modifications. Moreover, some Neo-Darwinists have elevated Natural Selection into a unique creative force that solves all the difficult evolutionary problems without a real empirical basis. Many scientists today see the need for a deeper and more complete exploration of all aspects of the evolutionary process.
I follow the posts of Intelligent Design Creationists in order to see whether they have finally begun to understand science. Imagine my excitement when this post appeared on the Science and Culture website!
Why Intelligence Is Necessary to Explain Nature’s Functional InformationAlas, my excitement was short-lived. The post is actually about a podcast interview with William Dembski and not somebody intelligent.
The first issue of Nature in 2026 has an article by science writer David Adam.
The Science of 2050 Nature explores the future breakthroughs that could shape our world.
The online version has a different title and subtitle but the text is the same. It begins with a quote from "futurologist" Nick Bostrum.
“There’s a good likelihood that by 2050, all scientific research will be done by superintelligent AI rather than human researchers. Some humans might do science as a hobby, but they wouldn’t be making any useful contributions.”
There's no attempt in the article to apply critical thinking to such a ridiculous prediction and the author doesn't consider the implications. If Bostrum (whoever that is) is right then that's the end of graduate studies and after 2050 nobody will be getting a Ph.D. in physics, biology, geology, or chemistry.
I hope I live long enough to see AI collecting and analyzing fossils in Greenland or studying volcanoes in Hawaii. Maybe I'll still be around when AI figures out how memories are stored or which transcription factor binding sites are functional in the human genome. And if I'm very, very lucky I'll see live to see all of my colleagues in the Department of Biochemistry abandon their labs and take up some scientific hobby like alchemy or intelligent design.
David Adam and the editors of Nature should be ashamed of themselves for publishing such nonsense.
There's been a lot of talk about how to teach science literacy. The discussion in the USA centers around STEM (science, engineering, technology, mathematics) and this acronym has also spread to other countries. It's an unfortunate development since there's a big difference between teaching science and teaching those other three topics.
Most studies suggest that we focus on teaching The Nature of Science (NOS). There's no definition of this topic that everyone agrees to but the essence is that students need to understand how our society generates knowledge. In the context of the natural sciences, this means understanding the process of discovery. There's general agreement that what this means is critical thinking that's evidence-based. It's another way of saying that we need to teach critical thinking and the importance of using evidence to back up and test your claims of knowledge. "Appreciating the scientific process can be even more important than knowing scientific facts. People often encounter claims that something is scientifically known. If they understand how science generates and assesses evidence bearing on these claims, they possess analytical methods and critical thinking skills that are relevant to a wide variety of facts and concepts and can be used in a wide variety of contexts.”The reasoning behind this emphasis is based on two pedagogical facts. The first is that it's impossible to teach all the facts and theories of a typical scientific discipline like astronomy or geology. It's pointless to make students memorize information that they will forget as soon as the class is over, Instead, as the argument goes, we need to teach students to understand how evidence is gathered and how it becomes fact. Teach students how to appreciate science and its power to create knowledge. That's something that will stick with them all their lives.
I'm a Canadian who's always been puzzled about American primaries. It seems to me that the purpose of these primaries is to help a political party choose its candidates for the next election. It seems like two of the parties, the Republican party and the Democratic Party, have managed to get state governments to fund their primary elections for reasons that are not very clear to those of us who live in other countries.
Today I was watching Michael Smerconish on CNN. He always has a poll question that provides a deep (and troubling) insight into his way of thinking. Today he announced that he is part of a class action lawsuit demanding that independent voters be allowed to vote in primary elections. That sounds weird to me because I'm used to a system where only members of a party get to choose who their candidates will be.
I was aware of the fact that many Americans see this differently and I knew that some states allow non-party members to pick the party candidate. Nevertheless, I was curious to see how CNN listeners would respond to his poll question.
Here are the results.
I find that result astonishing. 86% of respondents think they should be able to choose the candidate of the Republican or Democrat party even if they don't belong to one of those parties. What do they (you?) think is the purpose of primaries in the United States?
Here's a list of states and who they allow to vote in one of the primaries. It seems like the states actually have laws governing how political parties are able to choose their candidates.
I don't know of any other democracy that has such a bizarre system. I'm a member of one of the political parties in Canada and I participated in selecting our party leader. I would be outraged if my government passed a law allowing members of another party (or nonmembers) to help select my party leader or candidate. Why are such laws acceptable in the United States?
There's been so much bad news this week that I though you might enjoy a little humor to lighten your day. Here are some devout Young Earth Creationists making fun of some stupid comments they've found on the internet and calling on some professor to "destroy" evolutionists who believe in junk DNA [Latest in DNA Research Destroys Evolutionary “Proof”].
The expression of genes is regulated at many levels but one of the most important is regulation at the level of transcription. Transcription initiation is controlled by transcription factors that bind to sequences near the promoter and either activate or repress transcription.
A lot of work has been done on transcription regulation in mammals over the past 40 years. The general impression from these detailed studies of individual genes is that regulation usually involves a relatively small number of transcription factors that bind to sequences within 1000 bp or so of the transcription start site.
This model was challenged by the ENCODE studies in 2012. ENCODE researchers claimed to have discovered hundreds of thousands of cis-regulatory elements (CRE's) covering a substantial percentage of the genome. If they are correct, then this means that there are dozens of transcription factors controlling the expression of every gene.
I recently reported that Google's AI program does a horrible job of summarizing the junk DNA controversy. [The scary future of AI is revealed by how it deals with junk DNA] That led to a discussion about the "intelligence" in artificial intelligence and whether AI was capable of distinguishing between accurate and inaccurate data.
Google DeepMind is an artificial intelligence research laboratory headquartered in London, UK. Two of its programmers, Demis Hassabis and John Jumper, were awarded the 2024 Nobel Prize in Chemistry for developing AlphaFold, a program that predicts the tertiary structure of proteins.
Here's the post on Science & Culture (sic) by Casey Luskin: Happy New Year! No. 1 Story for 2025: Bombshell Overturns Myth of 1 Percent Difference.
How many times have you heard it said that the human and chimpanzee genomes are so similar that they are only “1 percent different” at the level of their DNA? This shows, we were told, not only that humans and chimps share common ancestry, but that humans aren’t all that special, which is a common talking point in science journalism and other public discussions. After all, we’re just slightly modified chimps! This “fact” has been discussed so much that it has become what the late biologist Jonathan Wells famously called an “icon of evolution.”
But now, new data reported in a recently published Nature paper by Yoo et al. has overturned this previous claim. The new findings reveal that human DNA is far more different from chimp DNA than previously thought.
That should be major news in the science world, yet those involved don’t seem interested in highlighting their discovery.
I complain a lot about the quality of science writing but today's post is very different. I want to highlight an article by Michael Le Page that he just published in New Scientist. It's one of the best articles on junk DNA that I've ever seen in popular science magazines and newspapers [Human-plant hybrid cells reveal truth about dark DNA in our genome].
I've admired Michael Le Page for many years because of his articles on climate change and evolution. It doesn't surprise me that he's right about junk DNA.
Today I did a Google search for the term "JUNK DNA" and, as usual, the first thing I saw was the Google AI description of junk DNA. It's wrong, but that's not the scary part. The most frightening thing about the AI description is that it promotes three videos that misrepresent science and two of them are from well known kooks.
What does this tell you about current versions of AI? It tells you that it is not intelligent in any meaningful sense of the word. It tells you that Google AI is incapable of distinguishing between scientific facts and ignorance. It tilts toward the loudest voices on the internet and, as we all know, those voices are frequently wrong.
There is considerable controversy over the total number of genes in the human genome. The number of protein-coding genes is pretty well established at somewhere between 19,500 and 20,000. It's the number of non-coding genes that's disputed.
There's general agreement on the number of well-defined small RNA genes such as snRNAs, snoRNA, microRNAs etc. Similarly, the number of ribosomal RNA and tRNA genes is known. The problem is with identifying genuine long non-coding RNA genes (lncRNA genes). Estimates vary from less than 20,000 to more than 200,000 but most of these estimates fail to define what they mean by "gene." Many scientists seem to think that any detectable transcript must come from a gene.
This doesn't make any sense since we know that spurious transcripts exist and they don't come from genes by any meaningful definition of gene. The only reasonable definition of a molecular gene is a DNA sequence that's transcribed to produce a functional product.1
The idea that spurious, non-functional, transcripts exist has been described in the scientific literature for many decades. One of my favorites is in a paper by Ponting and Haerty (2022) quoting another paper from thirteen years ago by Ulitsky and Bartel.
The cellular transcriptional machinery does not perfectly discriminate cryptic promoters from functional gene promoters. This machinery is abundant and so can engage sites momentarily depleted of nucleosomes and rapidly initiate transcription. The chance occurrence of splice sites can then facilitate the capping, splicing, and polyadenylation of long transcripts. A very large number of such rare RNA species are detectable in RNA-sequencing experiments whose properties are virtually indistinguishable from those of bona fide lncRNAs. Consequently, “a sensible [null] hypothesis is that most of the currently annotated long (typically >200 nt) noncoding RNAs are not functional, i.e., most impart no fitness advantage, however slight” (Ulitsky and Bartel, 2013: p. 26).
The important point here is that the correct null hypothesis is that these transcripts don't have a biologically relevant function and the burden of proof is on researchers to demonstrate function before assigning them to a genuine gene. My colleagues at the University of Toronto made the same point in a paper published in 2015.
In the absence of sufficient evidence, a given ncRNA should be provisionally labeled as non-functional. Subsequently, if the ncRNA displays features/activities beyond what one would expect for the null hypothesis, then we can reclassify the ncRNA in question as being functional. (Palazzo and Lee, 2015)
There are a number of well-defined lncRNAs that have been shown to have distinct reproducible functions. The key question is how many of these biologically relevant lncRNA genes exist in the human genome. I struggled with the answer to this question when I was writing my book. I finally decided to make a generous estimate of 5000 non-coding genes and that implies several thousand lncRNA genes (p. 127). I now think that estimate was far too generous and there are probably fewer than 1000 genuine lncRNA genes.
I have not scoured the literature for all the examples of human lncRNAs having good evidence of function but my impression is that there are only a few hundred. This post was incited by a recent publication by researchers from the Hospital for Sick Children and the University of Toronto (Toronto, Canada) who characterized another functional lncRNA called CISTR-ACT that plays a role in regulating cell size (Kiriakopulos et al., 2025).
I was prompted to revisit this controversy by the accompanying press release that said ...
Unlike genes that encode for proteins, CISTR-ACT is a long non-coding RNA (or lncRNA) and is part of the non-coding genome, the largely unexplored part that makes up 98 per cent of our DNA. This research helps show that the non-coding genome, often dismissed as ‘junk DNA’, plays an important role in how cells function.
We're used to this kind of misinformation2 in press releases but I thought it would be a good idea to read the paper. As I expected, there's nothing in the paper about junk DNA but here's the first sentence of the introduction.
The human genome contains more long non-coding RNAs (lncRNAs) than protein-coding genes (GENCODE v49) which regulate genes and chromatin scaffolding.
The latest version of GENCODE Release 49 claims that there are 35,899 lncRNA genes. This is the only reference in the Kiriakopulos et al. paper to the number of lncRNA genes. There's no mention of the controversy and none of the papers that discuss the controversy are referenced.
The GENCODE number is close to the latest version of Ensembl, which lists 35,042 lncRNA genes. I couldn't find any good explanation for these numbers or for the definition of "gene" that they are using but what's interesting is how these numbers are climbing every year; for example, a paper from two years ago listed a number of sources and you can see that the RefSeq and GENCODE numbers are much smaller than today's numbers (Amaral et al., 2023).3
It's perfectly acceptable to state your preferred view on lncRNAs when you publish a paper. The authors of the recent paper may want to believe that there are more lncRNA genes than protein-coding genes but I think it's important for them to define what they mean by "gene" when they make such a claim. What's not acceptable, in my opinion, is to ignore a genuine scientific controversy by not mentioning in the introduction that there are other legitimate views.
It's a shame that they didn't do that because their paper is a good example of the hard work that needs to be done in order to demonstrate that a particular lncRNA has a biologically relevant function.
In closing, I want to emphasize the recent review by Ponting and Haerty (2022)4 that points out the importance of the problem and the kinds of experiments that need to be done in order to establish that a given RNA comes from a real gene. This is how a scientific controversy should be addressed. Here's the abstract of that paper ...
Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. The majority of evidence, we argue, indicates that most lncRNA transcript models reflect transcriptional noise or provide minor regulatory roles, leaving relatively few human lncRNAs that contribute centrally to human development, physiology, or behavior. These important few tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, and so resist simple categorization. This genome-wide view should help investigators prioritize individual lncRNAs based on their likely contribution to human biology.
1. See Wikipedia: Gene; What Is a Gene?; Definition of a gene (again); Must a Gene Have a Function?.
2. No knowledgeable scientist ever said that all non-coding DNA was junk. We've known about non-coding genes for more than half-a-century.
3. See How many genes in the human genome (2023)?
4. See Most lncRNAs are junk
Amaral, P., Carbonell-Sala, S., De La Vega, F.M., Faial, T., Frankish, A., Gingeras, T., Guigo, R., Harrow, J.L., Hatzigeorgiou, A.G., Johnson, R. et al. (2023) The status of the human gene catalogue. Nature 622:41-47. [doi: 10.1038/s41586-023-06490-x]
Kiriakopulos et al. (2025) LncRNA CISTR-ACT regulates cell size in human and mouse by guiding FOSL2. Nature communications: (in press). [doi: 10.1038/s41467-025-67591-x]
Palazzo, A.F. and Lee, E.S. (2015) Non-coding RNA: what is functional and what is junk? Frontiers in genetics 6:2(1-11). [doi: 10.3389/fgene.2015.00002]
Ponting, C.P. and Haerty, W. (2022) Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review. Annual review of genomics and human genetics 23. [doi: 10.1146/annurev-genom-112921-123710Ulitsky, I. and Bartel, D.P. (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154:26-46. [doi: 10.1016/j.cell.2013.06.020]
The current best model of the human genome is that only 10% is functional and 90% is junk. This model was first developed over half a century ago (see Junk DNA). From the very beginning, the model recognized that regulatory sequences would make up a significant proportion of the functional elements but early suggestions that most of the repetitive DNA would turn out to be involved in regulation were rejected.
As more and more data accumulated on regulatory sequences, it became apparent that most regulatory sequences of pol II (RNA polymerase II) genes could be found in relatively short regions of DNA just upstream of the transcription start site. It also became apparent that for each transcription factor there were thousands of transcription factor binding sites even though only a small number were actually involved in genuine gene regulation.1
The mutation rate is approximately 100 new mutations per generation. Most of these will be neutral mutations that have no effect on the survival of the individual and almost all of them will be lost within a few generations. A small number of these neutral mutations will become fixed in the population and it's these fixed mutations that produce most of the changes in the genome of evolving populations. According to the neutral theory of population genetics, the number of fixed neutral mutations corresponds to the mutation rate. Thus, in every evolving population there will be 100 new fixed mutations per generation.
90% of the human genome is junk DNA.
Today I did a routine search for "junk DNA" "2025" to see if misinformation is still dominating the web. It is, but that's not the most surprising thing I discovered. Here's what Google AI told me at the top of the search page.
In 2025, "junk DNA" is no longer considered junk, as new studies show it plays vital roles in gene regulation and development. Research from 2025 indicates that these sequences, many of which come from ancient viruses, can act as "genetic switches" that influence how genes are turned on or off and how cells respond to their environment. This has led to potential breakthroughs in regenerative medicine and cancer treatment by providing new therapeutic targets.
This video explains how what was once considered junk DNA has been found to contain thousands of new genes:
The video is by Robert Carter who has a Ph.D. in molecular biology. His site is called Biblical Genetics. He also posts on creation.com
Carter sounds like he knows what he's talking about but he's just parroting all the misinformation that permeates the scientific literature. The main message of this video is that scientists were shocked to discover that the human genome only had 20,000 protein coding genes but we now know (no, we don't) that each gene makes many different proteins and that accounts for the "missing" complexity that all the experts had expected.1
We also "know" (no, we don't) that scientists have discovered tens of thousands of new protein coding genes that make small proteins. He references a Science article by Elizabeth Pennisi who has been spreading misinformation about the human genome for more than 25 years.
It's not surprising that Robert Carter wants to discredit the idea of junk DNA. What's surprising is that Google AI is directing readers to a creationist video.
1. The knowledgeable experts predicted that the human genome would have fewer than 30,000 genes and that's exactly what was found when the human genome sequence was published.
I'm giving a talk next Wednesday (October 1st) to the members of the Senior College (retired faculty). It's at the University of Toronto Faculty Club at 10am. I'll talk for 50 mins then there's a coffee break followed by 50 mins of questions and discussion.
Guests are welcome but you'll have to pay $10 to cover the cost of coffee and cookies. You can also register to watch my talk on Zoom. You can also stay for lunch at the Faculty CLub but you'll have to let me know so I can put you down as a guest.
Here's the link to register: What's in Your Genome?
Wednesday Talk: Wednesday, October 1, 2025, 10am-12pm.
In-person at the Faculty Club and on Zoom
Larry Moran, Biochemistry, University of Toronto
Title: “What’s in Your Genome?”
Abstract: Scientists have been studying the human genome for more than 70 years but today there is considerable controversy about what’s in our genome. The publication of the complete sequence of the human genome in 2001 did nothing to resolve the controversy. For many scientists, the data confirmed their predictions that we have about 30,000 genes and most of our genome is useless junk DNA. Other scientists were shocked to learn that we have so few genes so they began the search for other explanations. Today, the majority of molecular biologists and biochemists believe that most of our genome is functional and there may be as many as 100,000 extra genes that weren’t identified in 2001. The majority of experts in molecular evolution disagree —they believe that 90% of our genome is junk DNA. I will summarize the data from both sides of the controversy and discuss the role that science journalism has played in misrepresenting scientific discoveries about the human genome.
A recent paper on characterizing endogenous retrovirus sequences has attracted some attention because of a press release from Kyoto University that focused on refuting junk DNA. But it turns out that there's no mention of junk DNA in the published paper.
Let's start with a little background. Retroviruses are RNA viruses that go though a stage where their RNA genomes are copied into DNA by reverse transcriptase. The virus may integrate into the host genome and be carried along for many generations producing low levels of virus particles [Retrotransposons/Endogenous Retroviruses]. The integrated copies are called endogenous retroviruses (ERVs).
Our genome contains about 31 different families of ERVS that have integrated over millions of years. Most of the original virus genomes have acquired mutations, including insertions and deletions, and they are no longer active. These sequences account for about 8% of our genome.
The seven traits that Gregor Mendel worked with were: seed shape (R/r), cotyledon color (I/i), seed and flower color (A/a), pod shape (V/v), pod color (Gp/gp), flower position (Fa/fa), and stem length (Le/le). The last trait is also known as Tall (T) and short (t).
The genes for four of these traits (seed shape, cotyledon color, flower color, and stem length) were identified and characterized many years ago. The genes for the remaining three traits have now been identified. The results were published in the June 25, 2025 issue of Nature (Feng et al., 2025).
The transcripts of some genes can be alternatively spliced to produce more than one biologically functional product (e.g. proteins). There are several well-documented examples in the scientific literature but they are not common. There are probably fewer than 500 human genes (2.5%) that exhibit true alternative splicing where the alternate gene product has been conclusively shown to exist and be biologically functional.
However, it's easy to detect multiple examples of unusually spliced transcripts of humans genes. The vast majority of these splice variants are present at less than one copy per cell, are rapidly degraded, and not conserved in closely related species. That has led to the idea that they are simply the result of splicing errors, a conclusion that's reinforced by solid evidence that splicing is error prone.
In recent years, many scientists have come to realize that the role of alternative splicing has been greatly exaggerated. If you're interested in learning more, I cover the controversy on pages 154-169 in my book and in numerous blog posts (see below).
Unfortunately, there's a Nature editor who didn't get the message so they perpetuated the standard misinformation in a recent (May 21, 2025) editorial in Nature Reviews Genetics.
Anonymous (2025) RNA splicing — a central layer of gene regulation. Nat Rev Genet 26:369–370 [doi: 10.1038/s41576-025-00846-x]
... Splicing is essential for the accurate translation of DNA sequence information and comes with the added perk of generating transcriptomic and proteomic diversity in the form of alternative splicing — that is, the regulated inclusion or exclusion of exons. Alternative splicing greatly expands the coding potential of the genome; more than 95% of human multi-intron genes undergo alternative splicing, producing mRNA isoforms that can differ in coding sequence, regulatory elements or untranslated regions. These isoforms can influence mRNA stability, localization and translation output, thereby modulating cellular function.
... The ability of a single gene to produce several, functionally distinct protein isoforms through alternative splicing could enable organisms to rapidly adapt to changing environments. By enabling the sequencing of full-length transcripts, long-read sequencing data have yielded a more complete picture of alternative splicing. Subsequent comparative transcriptomic studies have revealed striking differences in the extent of alternative splicing between eukaryotes. Indeed, recent studies suggest that heritable variation in patterns of alternative splicing contributes to adaptive evolutionary chang.
Wouldn't it be nice if some leading researchers in the field wrote a scathing letter to Nature about the propagation of such misinformation? Does anyone know who to contact at Nature if you want to register a complaint?
Here's the problem. I can only access the cheap versions of AI such as ChatGPT and Scite Assistant but I can also see the results of Google's Generative AI whenever I do a Google search. Chris has access to more sophisticated versions so that's what he might be referring to when he says they operate at the Ph.D. level of intelligence.
There are three ways of estimating the human mutation rate. The Biochemical Method is based on the known error rate of DNA replication and the average number of cell divisions between generations. It gives a rate of about 130 mutations per generation.
The Phylogenetic Method assumes that a large fraction of mammalian genomes is evolving at the neutral rate because it is junk DNA. Since we know that the rate of fixation of neutral alleles is equal to the mutation rate, we can estimate the mutation rate if we know the total number of nucleotide difference between two species (e.g. humans and chimpanzees) and the approximate time of divergence from a common ancestor. This gives an estimate of about 112 mutations per generation.
It's a two hour video that discusses all the relevant topics on the human genome and junk DNA. The most exciting part for me comes at 56 mins when the moderator asks Casane and Laurenti to recommend a book on the subject (see screenshot on right). Patrick Laurenti suggests that my book should be translated into French but I don't think that's going to happen.
