Endogenous retrovirus sequences can be transcriptionally active: the reality vs. the hype

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 Most of the original virus genomes have acquired mutations, including insertions and deletions, and they are no longer active.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.

Predatory journals are helping to spread misinformation in the scientific literature

At the end of last year (2024) I posted an article about distinguished molecular biologist William Hasletine who published an article in Forbes about A New Dogma Of Molecular Biology: A Paradigm Shift. The article was about overthrowing the Central Dogma of Molecular Biology because of the discovery of thousands of non-coding genes. There is no paradigm shift. It's a paradigm shaft. [William Haseltine misrepresents molecular biology and calls for a paradigm shift]

Is AI really "intelligent"? Here are 13 biology questions to test the latest AI algorithms.

Last night I attended a talk by Chris DiCarlo who warned us about the dangers of AI. I'm sure he's right to be worried but I'm skeptical about some of the hype surrounding AI. For example, Chris said that just a few years ago the best AI algorithms were performing at high school level but now they are at Ph.D. level. The implication is that it won't be long before AI is smarter than humans.

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.

A new higher mutation rate in humans includes indels in repetitive DNA regions

Theme

Mutation

-definition
-mutation types
-mutation rates
-phylogeny
-controversies

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.

L'ADN poubelle: Junk DNA

This is a podcast in French on the topic of junk DNA. The moderator is Thomas C. Durand of La Tronche en Biais, a YouTube channel that focuses on critical thinking. Durand interviews two scientists from l’Université Paris Cité (City University of Paris), Didier Casane and Patrick Laurenti.

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.

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American Society of Human Genetics DNA Day essay contest winners

The American Society of Human Genetics sponsors an annual DNA Day Essay Contest. It's for grade 9-12 students from anywhere in the world.

This year's question is ...

Templeton Foundation funds a grant on transposons

The John Templeton Foundation supports "interdisciplinary research and catalyze conversations that enable people to pursue lives of meaning and purpose." Many of these projects have religious themes or religious implications. The foundation is well-known for its support of projects that promote the compatibility of science and religion. You can see a list of recent grants here.

Templeton recently awarded a grant of $607,686 (US) to study the role of transposons in the human genome. The project leader is Stefan Linquist, a philosopher from the University of Guelph (Guelph, Ontario, Canada). Stefan has published a number of papers on junk DNA and he promotes the definition of functional DNA as DNA that is subject to purifying selection [The function wars are over]. Other members of the team include Ryan Gregory and Ford Doolittle who are prominent supporters of junk DNA.

Tom Cech rejects junk DNA

A few months ago (June, 2024) I commented on an article by Tom Cech in The New York Times. [Tom Cech writes about the "dark matter" of the genome] In that article he expressed the view that 75% of the human genome consists of "dark matter" that is copied into RNAs of unknown function. He believes that many of these mysterious RNAs will turn out to have exciting functions.

I suspected that Cech is opposed to junk DNA and that suspicion is confirmed in his new book The Catalyst.

Google's "Generative AI" lies about junk DNA

Every now and then I check Google to see if there's any news about junk DNA. I use "junk DNA" as my search query.

The first thing I see at the top of the results page is a summary of the topic created by Google's Generative AI, which it claims is experimental. The AI summary is different every time you start a new search but all of the responses are similar in that they criticize the idea of junk DNA. Here's an example from today,

The misinformation spread by ENCODE in 2012 is gradually being recognized

I want to draw your attention to an excellent online book on bacterial genomes: Bacterial Genomes:Trees and Networks. The author is Aswin Sai Narain Seshasayee of the National Centre for Biological Sciences at the Tata Institute of Fundamental Research in Bangalore, India. Here's a link to Chapter 3: The genome: how much DNA? where he explains why bacterial genomes don't have very much junk DNA.

The chapter contains an excellent summary of the history of genome sizes in bacteria and eukaryotes and a detailed description of both the c-value paradox and the mutation load arguments. The relationship between junk DNA and population size is described.

I was especially pleased to see that the author didn't pull any punches in describing the ENCODE publicity campaign and their false statements about junk DNA.

In 2012, a post-human-genome project called ENCODE, which aims to experimentally identify regions of the human genome that undergo transcription—or are bound by a set of DNA-binding proteins, or undergo chemical changes called epigenetic modifications—came to a stunning conclusion that at least 80% of the human genome is functional and that it was time to sing a requiem for the concept of junk DNA! However, this conclusion, which has been severely criticised since its publication, ignores decades of well-supported arguments from evolutionary biology arising from the c-value paradox, some of which we have described here or will do so shortly; it does not quite explain why this conclusion—if broadly applied to the genomes of other multicellular eukaryotes—would not imply that a fish needs 100 times as much functional DNA as a human; and plays “fast and loose” with the definition of the term ‘function’. While the ENCODE project, a great success in many ways, has provided an invaluable resource for the study of human molecular biology, we can safely ignore its ill-fated conclusion on what fraction of the human genome is functional.

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Junk DNA is gradually making its way into mainstream textbooks

The idea that most of the human genome is junk originated more that 50 years ago. Since then, evidence in support of this concept has steadily accumulated but it has been stongly resisted by most biochemists and molecular biologists. Opposition is even stronger among scientists in other fields and in the general public thanks to a steady stream of anti-junk articles in the popular press.

Much of this opposition to junk DNA stems from a massive publiciy campaign launched by ENCODE researchers and the leading science journals back in 2012.

It's likely that most of the controversy over junk DNA is related to differing views on evolution and the power of natural selection. Most people think that natural selection is very powerful so that modern species must be extremely well-adapted to their present environment. They tend to believe that complexity is simply a reflection of sophisticated fine-tuning and this must apply to the human genome. According to this view, the presence of huge amounts of DNA with an unknown function is just a temporary situation and in the next few years most of this 'dark matter' will turn out to have a function. It has to have a function otherwise natural selection would have eliminated it.

Why Trust Science?

Bruce Alberts,¹ Karen Hopkin, and Keith Roberts have published an essay on Why Trust Science.

In this essay, we address the question of why we can trust science—and how we can identify which scientific claims we can trust. We begin by explaining how scientists work together, as part of a larger scientific community, to generate knowledge that is reliable. We describe how the scientific process builds a consensus, and how new evidence can change the ways that scientists—and, ultimately, the rest of us—see the world. Last, but not least, we explain how, as informed citizens, we can all become “competent outsiders” who are equipped to evaluate scientific claims and are able to separate science facts from science fiction.

Most of the essay describes an idealized version of how science works with an emphasis on collaboration and rigorous oversight. They claim that the work of scientists can usually be trusted because it is self-correcting.

Intelligent Design Creationists launch a new attack on junk DNA (are they getting worried?)

The Center for Science and Culture (sic) and the Discovery Institute (sic) have published another propaganda video on junk DNA. The emphasis is on their claim that ID predicted a functional genome and that prediction turned out to be correct! The difference between this video an previous attempts to rationalize their failures is that I now get a personal mention and a caricature in this latest video.

I think I understand the problem. The ID creationists are getting worried about junk DNA as they realize that more and more scientists are beginning to understand the real problems with the ENCODE data and previous claims of function. This is why they are attempting to rebut the science behind junk DNA. But the real problem is that they simply don't understand the science as you can see in the video.

Once again, we are faced with a question about whether Intelligent Design Creationists are stupid or lying (or both).

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BREAKING NEWS: Intelligent Design Creationists claim that this year's Nobel Prize refutes junk DNA and confirms IDC predictions!

This is a Come Let Us Reason Together (sic) podcast moderated by Lenny Esposito with Faxale "Fuz" Rana of Reasons to Believe and Casey Luskin of the Discovery Institute. They discuss this year's Nobel Prize for the discovery of microRNAs and "how it supports intelligent design and weakens the evolutionary paradigm." Casey Luskin devoted a post to the topic on the Discovery Institute propaganda blog: 2024 Nobel Prize Awarded for the Discovery of Function for a Type of “Junk DNA”.

Enjoy! (Spot the lies.¹)

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1. In Luskin's case, we know he is lying. [Is Casey Luskin lying about junk DNA or is he just stupid?]

William Haseltine misrepresents molecular biology and calls for a paradigm shift

William Hasletine is a well-respected molecular biologist with an outstanding track record dating back to the time when he was a graduate student under Jim Watson and Wally Gilbert where he studied the regulation of gene expression in bacteria (Ph.D. in 1973). This is why I was surprised to see his recent article in Forbes where he seems to have fallen hook-line-and-sinker for postgenomics gobbledygook. It looks like Haseltine is losing the ability to think critically as he concentrates more on technology and public policy.

A New Dogma Of Molecular Biology: A Paradigm Shift by William A. Haseltine

The "wisdom" of the Discovery Institute

John G. West is Vice President of the Discovery Institute and one of the founding members of the Center for Science and Culture. He is a leading proponent of Intelligent Design Creationism.

West has reviewed the latest book by Francis Collins; the review was published in The Federalist. [Francis Collins’ Latest Book Doubles Down On His Massive Abuses Of Power]

Science journal tries to understand misinformation

The November 1, 2024 issue of Science contains three articles on misinformation in science. The articles tend to concentrate on the standard examples such as vaccine misinformation but there's another kind of misinformation that's just as important. I'm talking about scientific misinformation that's spread by journals like Science and Nature.

Do any of you remember the arsenic affair? That's when science accepted a paper by Felisa Wolfe-Simon and her collaborators claiming that they isolated a bacterium that substituted arsenic for phosphorus in its DNA. The paper was published online and was severely criticized after a ridiculous NASA press conference. It was eventually refuted when Rosie Redfield and others looked closely at the bacterial DNA and showed that it did not contain arsenic. The paper has still not been retracted. [See Reviewing the "Arseniclife" Paper.]

And let's not forget the massive misinformation campaign associated with the publication of ENCODE results in 2012.

Do plants have junk DNA?

Current Opinion in Plant Biology has a special edition devoted to Genome studies and molecular genetics 2024. The only paper (so far) that discusses plant genomes is one devoted to RNAs. Here's the abstract ...

Anyatama, A., Datta, T., Dwivedi, S. and Trivedi, P.K. (2024) Transcriptional junk: Waste or a key regulator in diverse biological processes? Current Opinion in Plant Biology 82:102639. [doi: 10.1016/j.pbi.2024.102639]

Plant genomes, through their evolutionary journey, have developed a complex composition that includes not only protein-coding sequences but also a significant amount of non-coding DNA, repetitive sequences, and transposable elements, traditionally labeled as “junk DNA”. RNA molecules from these regions, labeled as “transcriptional junk,” include non-coding RNAs, alternatively spliced transcripts, untranslated regions (UTRs), and short open reading frames (sORFs). However, recent research shows that this genetic material plays crucial roles in gene regulation, affecting plant growth, development, hormonal balance, and responses to stresses. Additionally, some of these regulatory regions encode small proteins, such as miRNA-encoded peptides (miPEPs) and microProteins (miPs), which interact with DNA or nuclear proteins, leading to chromatin remodeling and modulation of gene expression. This review aims to consolidate our understanding of the diverse roles that these so-called “transcriptional junk” regions play in regulating various physiological processes in plants.

Philip Ball's view of alternative splicing

Genomics is a powerful tool that allows you to collect massive amounts of data that can point the way to new understanding. But it can also be abused when the results are overinterpreted. We saw an extraordinary example of this in 2012 when ENCODE made unsubstantiated claims that were quickly challenged.

I'm reminded of the caution from Sydney Brenner who warned us about genomics (Brenner, 2000) and the warning in Dan Graur's harsh critique of the 2012 ENCODE claims (Graur et al., 2013) where they said ...

The Editor-in-Chief of Science, [Bruce Alberts,] has recently expressed concern about the future of "small science," given that ENCODE-style Big Science grabs the headlines that decision makers so dearly love. Actually the main function of Big Science is to generate massive amounts of easily accessible data. The road from data to wisdom is quite long and convoluted. Insight, understanding, and scientific progress are generally achieved by "small science." ...

Three lungfish species have huge genomes

Lungfish are our closest living fish cousins. All living terrestrial vertebrates (e.g. amphibians, mammals, reptiles) descent from a common ancestor with lungfish. The split occurred about 400 million years ago (4Ma) (Devonian) when there were 70-100 different lungfish species.

This relationship (lungfish-tetrapods) was firmly established recently by comparing the genome of the Australian lungfish (Neoceratodus forsteri) with that of tetrapods (Meyer et al., 2021). The other possibility had been ceolacanth-tetrapods. Coelacanths and lungfish are related—they form the class Sarcopterygii (lobe-finned fish).