My book manuscript has been reviewed by some outside experts and they seem to have convinced my editor that my book is worth publishing. I hope we can get it finished soon. It would be nice to publish in in September on the 10th anniversary of the ENCODE disaster.
Meanwhile, I keep scanning the literature for mentions of junk DNA to see if scientists are finally coming to their senses. Apparently not, and that's a good thing because it means that my book is still needed. Here's the opening paragraph from a recent review of lncRNAs. The authors are in the Department of Medicine at the Medical College of Gerogia, in Augusta, Georgia (USA).
Ghanam, A.R., Bryant, W.B. and Miano, J.M. (2022) Of mice and human-specific long noncoding RNAs. Mammalian Genome:1-12. [doi: 10.1007/s00335-022-09943-2]
Approximately ninety-eight percent of our genome is noncoding. Contrary to initial descriptions of this vast sea of sequence comprising “junk DNA” (Ohno 1972), comparative genomics and various next-generation sequencing studies have revealed millions of transcription factor binding sites (TFBS) (Vierstra et al. 2020) and tens of thousands of noncoding genes, most notably the class of long noncoding RNAs (LncRNAs), defined currently as processed transcripts of length > 200 base pairs with no protein-coding capacity (Rinn and Chang 2020; Statello et al. 2021). The widespread transcription of LncRNAs and abundance of regulatory sequences such as enhancers support the concept of a genome that is largely functional (ENCODE Project Consortium 2012). Such a dynamic genome should not be surprising given the complex nature of gene expression and gene function necessary for embryonic and postnatal development as well as disease processes.
- No reasonable scientist, especially Susumu Ohno, ever said that all noncoding DNA was junk.
- There are millions of transcription factor binding sites but most of them are spurious binding sites that have nothing to do with regulation. They simply reflect the expected behavior of typical DNA binding proteins in a large genome full of junk DNA.
- Nobody has demonstrated that there are tens of thousand of noncoding genes. There may be tens of thousands of transcripts but that's not the same thing since you have to prove that those transcripts are functional before you can say that they come from genes.
- There is currently no evidence to support the concept of a genome that is largely functional in spite of what the ENCODE researchers might have said ten years ago.
- Such a genome would be very surprising, if it were true, given what we know about genomes, evolution, and basic biochemistry.
Except for those few minor details—I hope I'm not being too picky—that's a pretty good way to start a review of lncRNAs. :-)
21 comments :
This is good news. can't wait to read it.
What Rumraket said.
Cool! I look forward to reading it. Getting tired of the creationist "there is no junk DNA" mantra...
Congratulations on the book. It can't be published soon enough. Of course the big hurdle is getting all the molecular biologists to read it.
I don't know how many lncRNAs there are, or how long they are, but assuming 50,000 in the human genome, at about 400 base pairs each, we get 20 million base pairs of lncRNA. That seems an insignificant fraction of the human genome. Barely a blip.
Number of papers and researchers that argue against the "junk" status of majority genome keeps on increasing.
If majority of our genome is functional, then the arguement against Design collapses. No critic can then argue: "Why would the designer put chunks of non-functional elements in our genome?"
If the majority of our genome isn't functional, does the argument for design collapse? Asking for a friend.
Tell your friend that the Designer may have an inordinate fondness for transposons.
The are two kinds of design arguments. The most obvious one is Intelligent Design Creationism but a more pernicious one is the Richard Dawkins' argument from design. Dawkins proposes that just about everything is designed by natural selection and that's why he's been very skeptical about junk DNA.
Design theorists still need to take on the Graur challenge.
"Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 − 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these “functional” regions or because no mutation in these regions can ever be deleterious."
-Dan Graur, "On the Immortality of Television Sets: “Function” in the Human Genome According to the Evolution-Free Gospel of ENCODE"
It would be interesting to hear Design theorists explain how DNA sequence can be randomly mutated for eternity without ever losing function.
Congratulations on the book, Larry.
Wow, Diogenes. Haven't seen you post since 2015 or so! Glad to see you're back.
seconded
I appreciate the thoughts. I got out of arguing with creationists about the time Trump won the election and spent too much time arguing with Trumpers and conspiracy theorists.
For the United States, Trumpism was like the zombie apocalypse that science fiction movies warned us about.
They're everywhere, they're clawing at the windows, and your friends and loved ones are transformed.
"That's my dear cousin! I grew up with him"
"That thing is not your cousin anymore. It's one of them now"
Obviously not over yet
Welcome back Diogenes.
Sandwalk readers might not know that Diogenes is in my book.
"While it’s true that there are some scientists who agree with Mattick, it’s extremely misleading to imply that the majority of scientists think this way. However, the tactic used by Mattick and his collaborators is a useful ploy for those people who want to argue for so-called “revolutionary” ideas like the discovery of functional RNAs and the rejection of junk DNA. They set the stage by describing a (false) paradigm that supposedly dominated thinking up until recently. This makes new ideas look like a “paradigm shift” when it is exploited by these writers.
A person who goes by the name “Diogenes” is one of the frequent commenters on my Sandwalk blog and he coined a very useful term for this trick of setting up a strawman to make your ideas look revolutionary. He calls it a 'paradigm shaft.' "
I look forward to reading it! I know that different cell types show very divergent epigenetic patterns (e.g. DNA methylation) yet these cell types differences being conserved across species. I totally agree that epigenetic signatures do not necessarily indicate “function” but I was wondering how these patterns has been conserved for a long period of time. Could you let me know how to interpret this? I am asking this question purely from my curiosity.
You'll probably enjoy Chapter 10; especially the section on "What the heck is epigenetics?" I have included a quotation from Kat Arney in her book "Herding Hemingway's Cats."
"Over the past few decades the concept of epigenetics has caught on in the scientific world like a particularly aggressive rash. It’s even nudging its way into the public consciousness thanks to breathless articles warning of the epigenetic effects of everything from stress to sunshine, exhorting us to pimp our genomes by drinking green tea or munching broccoli. References to epigenetics have leaked into newspapers, seeped into medicine, and contaminated fields such as psychology and even sociology. More alarmingly, purveyors of pseudoscience are jumping on the epigenetic bandwagon, and the word seems to be used increasingly in the same way that certain people bandy about the term ‘quantum’ as a hand-waving non-explanation for mysterious things they don’t really understand. As a scientist, I worked on epigenetics before it was cool, and I find this infuriating."
Prof Moran have you seen the article on genome size (focused on Salamanders) in Scientific American? I found the emphasis that the salamanders were mal-adapted very much in the adaptionist paradigm.
https://www.scientificamerican.com/article/junk-dna-deforms-salamander-bodies/
I don't read Scientific American.
OMG. You still believe most DNA is junk.
@Anonymous
OMG! You don't!
Buy my book.
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