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.

Although we can't see it, we know that dark matter matters, at least when it comes to thinking about astronomy. As it turns out, our genome also largely consists of "dark matter." The coding regions of all the human genes that specify proteins make up only about 2 percent of our genome. When we add the introns that interrupt those coding regions—the sequences that are spliced out after the DNA is transcribed into the precursors to mRNA—we account for another 24 percent. That leaves about three-quarters of the genome that is "dark matter." For decades this 75 percent was dismissed as "junk DNA" because whatever function it had, if any, was invisible to us.

But as the technologies for sequencing RNA have improved, scientists have discovered that most of this dark-matter DNA is in fact transcribed into RNA. Some portion of this DNA is copied into RNA in the brain, other portions in muscle, or in the heart, or in the sex organs. It’s only when we add up the RNAs made in all the tissues of the body that we see the true diversity of human RNAs. The total number of RNAs made from DNA’s "dark matter" has been estimated to be several hundred thousand. These are not messenger RNAs, but rather noncoding RNAs—the same general category as ribosomal RNA, transfer RNA, telomerase RNA, and microRNAs. But what they’re doing is still, for the most part, a mystery.

Cech then goes on to say that that these mysterious RNAs are long non-coding RNAs or lncRNAs and he mentions a few lncRNAs that have a known biological function. This is misleading because it doesn't distinguish between real functional lncRNAs and spurious transcripts that have no function. By calling them all lncRNAs, he implies that they might have a function thus ruling out the null hypothesis of non-function. It would be better to say that some of these transcripts may turn out to be lncRNAs.

He is not unaware of the fact that others may disagree with his speculations and I have to give him credit for at least bringing it up.

As a result, many scientists do not share my enthusiasm for these RNAs. They think that RNA polymerase, the enzyme that synthesizes RNA from DNA, makes mistakes and sometimes copies junk DNA into junk RNA. A more scholarly description of such RNAs might explain them away as "transcriptional noise"—the idea being, again, that RNA polymerase isn't perfect. It sometimes sits down on the wrong piece of DNA and copies it into RNA, and that RNA may have no function. I readily admit that some of those lncRNAs may in fact turn out to be noise, berift of function, signifying nothing.

However, I'll point out that there was a time in the not-to-distant past when telomerae and micrRNAs and catalytic RNAs weren't understood. They hadn't been assigned any function. They, too could have been dismissed as "noise" or "junk." But now hundreds of research scientists go to annual conferences to talk about these RNAs, and biotech companies are trying to use them to develop the next generation of pharmaceuticals. Certainly one lesson we've learned from the story of RNA is never to underestimate its power. Thus, these lncRNAs are likely to provide abundant material for future chapters in the book of RNA.

This is a weak argument because it assumes that there's no evidence for junk DNA. He describes it as "dark matter" thus laying the groundwork for future discoveries that might find function. However, 90% of the genome is not dark matter; it is junk DNA and there's abundant evidence to support that claim. Cech should not be dismissing the fact that these unknown transcripts come from a part of the genome that's junk DNA. He has to deal with that if he wants to be credible.

He's also ignoring the glaring issues with most of these transcripts. They have been well-documented in the scientific literature (Palazzo and Lee, 2015) and I cover them in my book [Chapter 8: Noncoding Genes and Junk RNA]. The points that need explaining are ...

• Most of the transcripts are present at very low abundance, often less than one copy per cell.
• The RNAs are not conserved. Homologous regions in related species are not transcribed. Furthermore, there's no evidence that these regions are subject to purifying selection.
• Most of the transcripts are confined to the nucleus of cells and they are turned over rapidly, just as you would expect if they are spurious transcripts.
• After several decades of intensive study, only a small number of these transcripts in any one species have been shown to have a biological function. That doesn't mean that functions for some of them won't be found in the future but the lack of progress so far is consistent with the idea that most of them don't have a function and inconsistent with the idea that tens of thousands have a function that's just waiting to be discovered by all those reasearch scientists that go to the annual conferences.

For more information, read my blog posts on a 2024 paper by Nils Walter (Walter, 2024) where I discuss the evidence for and against the idea that our genome contains tens of thousands of non-coding genes.

• Nils Walter disputes junk DNA: (1) The surprise
• Nils Walter disputes junk DNA: (2) The paradigm shaft
• Nils Walter disputes junk DNA: (3) Defining 'gene' and 'function'
• Nils Walter disputes junk DNA: (4) Different views of non-functional transcripts
• Nils Walter disputes junk DNA: (5) What does the number of transcripts per cell tell us about function?
• Nils Walter disputes junk DNA: (6) The C-value paradox
• Nils Walter disputes junk DNA: (8) Transcription factors and their binding sites
• Nils Walter disputes junk DNA: (9) Reconciliation

Note: It should come as no surprise that the Intelligent Design Creationists have picked up on Cech's views and claim him as one more example of a leading scientist who agrees with their view that most of the human gnome is functional. [Nobelist Thomas Cech on “Junk RNA”] They also quote him as confirming their crazy claim that the 'false' idea of junk DNA retarded scientific progress.

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Walter, N.G. (2024) Are non‐protein coding RNAs junk or treasure? An attempt to explain and reconcile opposing viewpoints of whether the human genome is mostly transcribed into non‐functional or functional RNAs. BioEssays:2300201. [doi: 10.1002/bies.202300201]

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]