RNA-targeting CRISPR reveals that noncoding RNAs are not 'junk'
phys.org
phys.org
But it remains true that there are large amounts of non-coding junk DNA which is under no selection pressure. It may be important for spacing out sections of DNA or it may just be along for the ride after being incorporated by ancient splicing errors or viruses. It's just frustrating to keep reading this articles about how, "it's not junk after all," when it has been known for decades that DNA/RNA have many non-coding functions and it has also been known for decades that there truly is "junk" DNA.
For people who may not understand how we know this -- there are "conserved" sections of DNA which don't change much over time. Very similar in mice and humans for example, because it performs important regulatory work, and if it doesn't, the animal dies.
There are other large sections where it can disappear and nothing of consequence seems to happen. And we know that, because some people have micro-deletions or other variants in the region and they are completely benign.
We will eventually identify a better classification than "intron" and "exon" to sort through the "junk" from "critical junk" but we are really only starting to untangle the situation.
So then we don't know for sure? I thought surely we must have some more rigorous means of identifying junk for OP's comment to be true, but trial and error removal seems really weak.
Not really productive to imagine scenarios to unlock some hidden use. Sometimes junk is junk. Evolution is not hyper-efficient in the short term, stuff happens.
> "conserved" sections of DNA which don't change much over time
I'm not a biologist. I imagine DNA that does nothing and is under no selection pressure should have a bunch of random mutation accumulated - the opposite of what you described.
We don't need 1M copies of Alu: https://en.wikipedia.org/wiki/Alu_element
A lot of the sequences are defective copies. These are often how new genes arise, but they are not useful to the individual.
Nope, you cannot ever assert that.
Did you understand the article? What was once thought to be junk turned out not to be. Extrapolate from that.
The single most common sin in all of science is to misrepresent the null hypothesis because it makes getting positive results easy. In article form, this translates to when you see a title "Everyone thought X but actually Y," 99% of the time nobody thought X and Y is otherwise unremarkable. They wanted to remark on Y, though, so they cooked up "Everyone Thought X" to facilitate the presentation.
What? Like ... not at all? Onus does not get assigned "by default" due the nature of things, lol. The onus falls on whoever comes up to propose an hypothesis.
In this case that hypothesis is "all other DNA/RNA is junk", well, then "prove that thing is true", which is unfeasible and hence why one could not assert such thing.
Strawman.
It is not as black and white as you think it is. Some non-coding DNA/RNA is functional. Some is not. Selection/conservation is often used as quick way to tell whether something is functional or not.
Nobody actually in the field of genetics would say "all other DNA/RNA is junk". You'd get laughed out of the room, kind of in the same way if you said "all non-coding DNA is functional because 'epigenetics' ".
There's an abysmal number of post-transcriptional effects that are functional. Start with something like [1].
There's also plenty of evidence (like TFA and [2]) of "junk" DNA turning out to be functional through some contrived and completely unexpected mechanisms.
Every time someone says something like "this is how Biology works" one can lmao all the way to the lab.
From my reference below: "If most eukaryotic DNA is functional at the organism level, be it for gene regulation, protection against mutations, maintenance of chromosome structure, or any other such role, then why does an onion require five times more of it than a human?"
Of course, one can always say, "How arrogant to think we know everything." But given our current understanding of evolution and genetic function, the specific identity of a genetic sequence correlates with its function. If that function is important, the sequence should be preserved to a degree better than random chance.
To deny this is to suggest that any random sequence of genetic material can serve a vital purpose while being subject to endless mutation without consequence. This raises the question: What do we mean by a "specific sequence" if it isn’t conserved and is constantly mutating?
I assume you are familiar with the information I’ve just shared. I’m curious where we are diverging in our views because it feels like we are not discussing the same thing.
This artcle fairly represents my understanding of what I mean when I say "junk DNA": https://journals.plos.org/plosgenetics/article?id=10.1371/jo...
[1] https://sandwalk.blogspot.com/2022/08/junk-dna-vs-noncoding-...
[2] https://en.wikipedia.org/wiki/Junk_DNA#History
[3] https://judgestarling.tumblr.com/post/154553548091/long-nonc...
Genetic engineering always had the problem that you just don't want to express a gene that makes a protein but you want to express that gene a lot. For instance the first version of Golden Rice produced detectable but not nutritionally significant amounts of Vitamin A. It took them quite a few more years to get Golden Rice 2 which produces enough to matter.
It's been known a long time that a lot of genes associated with diseases are non-coding, but looking at what my RSS reader shows me it seems that very rapid progress is being made right now on understanding these hidden regulatory networks.
https://phys.org/biology-news/
for example https://phys.org/news/2024-12-microrna-evolutionary-mystery-...
> It may be important for spacing out sections of DNA
Is it possible that there IS selection pressure for unread DNA? I could imagine that cells with comparatively huge chromosomes last a bit longer, since you'd hope that some percentage of those pairs are just cannon fodder for the usual mutagenic sources. (energy, viruses, being a European king, etc) Like you can either make the bullseye on the target smaller, or spread out the points across the whole face of the target.
Again, no idea what I'm talking about, but maybe the researchers here are seeing a breakdown in the "control characters" around these parts? Maybe there's a sort of null start/null terminate at both ends in the "real" DNA, and when it breaks down, these unintended sacrificial spacers get parsed.
Inbreeding is a problem of not enough mutation, not a problem of too much.
How is it known that there truly is junk dna?
Rates of mutation in these regions, and lack of conservation are hallmark clues which show that there isn't function in these regions. That doesn't mean totally useless, these non-functional regions provide the raw material for the creation of genes and functional elements. Its just that, right now, those regions aren't doing anything.
No biologist calls it "junk DNA". That is just a simplified layman's term for media press releases.
This isn’t just “we don’t know what it does, so it must be junk.” It’s more like, “We can’t find any sign that it matters, and everything we know about evolution says if it mattered, we’d see fewer random changes there.” Down the road we might uncover small roles for some of these regions, but at this point, calling them junk is just an honest read of the evidence we have.
Over long evolutionary or environmental timeframes, these sequences may take on important functions, potentially becoming critical under conditions we can't currently foresee.
Anyways there definitely are non-coding regions that just don’t do much and evolve neutrally. I’m hesitant to call them junk but only because that designation has burned biologists so many times.
To borrow an example: an onion likely doesn’t need 5x more DNA than a human, and a lungfish probably doesn’t need 30 times more than we do (and 350x more than a pufferfish). And yet, these enormous genomes exist. It’s very likely that portions of these sequences are what we’d call “junk,” i.e., DNA that doesn’t confer a meaningful functional advantage and can accumulate due to the relatively low cost of carrying it along.
If we want to avoid the term “junk,” we could say something like “areas of the genome for which we assign a very low prior probability of functional importance.” But “junk” is a concise shorthand to acknowledge that, while some non-coding sequences matter, there are also huge swaths of DNA in many eukaryotes that show no signs of being anything other than evolutionary baggage.
Bacteria have high population sizes. Selection can be quick and brutal. Low levels of “code of unknown function” in bacteria is perhaps related to replicative efficiency. Fast DNA replication is highly advantageous in nutrient-rich environments. No space (or time) for junk DNA.
But the rate of mutation is itself subject to selection. There isn't a base rate, just a setting that's different for different parts of the genome. Some parts have more copy errors than other parts. Some are hung out in the sun more often.
So you can conclude from the mutation rate of a particular stretch that it would probably be bad if it started mutating more, and that it would probably be bad if it started mutating less, but not that nothing's influencing the mutation rate.
The idea that you can have DNA of some critter and there aren't some errors, unused bits, and so on, after what must be trillions of copies, well, I would find it statistically unlikely. Like saying you have a program with millions of lines of code and it is completely error-free.
Furthermore, in rats and mice, large swaths of junk DNA have been experimentally removed, without any detectable effect on the phenotype.
If the junk DNA has any positive effect, it may be to protect against viruses or transposons inserting themselves into random areas of the genome. Keeping the majority of DNA "useless" may decrease the risk that these insert themselves into vital parts of the DNA.
> A gene is defined as any portion of chromosomal material that potentially lasts for enough generations to serve as a unit of natural selection. In the words of the previous chapter, a gene is a replicator with high copying-fidelity. Copying-fidelity is another way of saying longevity-in-the-form-of-copies and I shall abbreviate this simply to longevity. The definition will take some justifying.
> On any definition, a gene has to be a portion of a chromosome. The question is, how big a portion—how much of the ticker tape? Imagine any sequence of adjacent code-letters on the tape. Call the sequence a genetic unit. It might be a sequence of only ten letters within one cistron; it might be a sequence of eight cistrons; it might start and end in mid-cistron. It will overlap with other genetic units. It will include smaller units, and it will form part of larger units. No matter how long or short it is, for the purposes of the present argument, this is what we are calling a genetic unit. It is just a length of chromosome, not physically differentiated from the rest of the chromosome in any way.
> Now comes the important point. The shorter a genetic unit is, the longer—in generations—it is likely to live. In particular, the less likely it is to be split by any one crossing-over. Suppose a whole chromosome is, on average, likely to undergo one cross-over every time a sperm or egg is made by meiotic division, and this cross-over can happen anywhere along its length. If we consider a very large genetic unit, say half the length of the chromosome, there is a 50 per cent chance that the unit will be split at each meiosis. If the genetic unit we are considering is only 1 per cent of the length of the chromosome, we can assume that it has only a 1 per cent chance of being split in any one meiotic division. This means that the unit can expect to survive for a large number of generations in the individual’s descendants. A single cistron is likely to be much less than 1 per cent of the length of a chromosome. Even a group of several neighbouring cistrons can expect to live many generations before being broken up by crossing over.
[end quote]
I think a reasonable extrapolation from this is that “genes” (things that are subject to natural selection in our genome) can survive more generations if they are surrounded by genetic material that are not “genes” (ie. Their copying fidelity is not subject to any selection pressure.)
If a gene in this sense is recombined in a way that makes it no longer the same gene, it most likely isn’t going to be beneficial to the organism (and thus the gene’s longevity.) Most genetic mutations aren’t.
Highly recommend David Reich’s book for are good overview of the math of recombination in humans.
I got into Dawkins’ books initially from The God Delusion (as I suspect many laypeople), and heard about The Selfish Gene from there, so evolutionary biology is not my area.
It makes sense that TSG is considered the dark ages as it’s such an old book. I was always curious to read more about the topic from other — and hopefully more recent — biologists, since Dawkins sometimes feels like he’s more of a communicator than a practicing biologist (and one with a particularly anti-religious chip on his shoulder, not that he’s wrong.)
Yes, we find the significance of DNA by knocking it out and seeing what happens.
Yes, crispr/cas-9 or /cas13 can be used for knocking out.
Yes, it's interesting to compare across models to find relatively conserved behaviors.
That's all known and done.
What could be interesting about these results is exactly how they achieved scale and variety at reasonable time and cost. Labs typically build expertise in a particular model organism, and it's very hard to get things right in many cell types, no less to run essentially thousands of experiments. Developers have a vague sense of 3nm semiconductor process and the potential for on-chip memory (both yield/quality and potential), but we (I) have no sense how good the process is underlying findings like this.
Junk DNA can be vestigial. It had a purpose. It no longer does. If there's no selective pressure to get ride of it, it will remain, adrift. The belief that because it exists it must have a purpose could be a human bias
That they weren’t needed was another myth. They turned out to be helpful at stopping one of the main killers of early humanity: diarrhea. Still kills lots of people in the third world. Appendix helps prevent stomach problems, too. Quite a few people whose were removed figured that out on their own.
I guess what I’m wondering how we can be sure that structure is function but non-coding structure has no function and exerts no selective pressure - isn’t the Golgi apparatus analogously “non-coding”?
Biology is more complicated than maths/physics. Multiple extinction crises that shaped the world are still written into our genome and there can be very subtle adaptations at play.
People with certain patterns in their non-coding DNA are at much higher risk of ALS, a terrible disease [0] - it certainly looks that at least this part of DNA plays some role in our organisms.
I don't know about the spine, is it really? Because the whole system looks very optimized for running upright to me, pretty much a perfect running machine.
it's so stupid to assume they were junk. but it's by no means lonely as an example.
Merely limiting the tremendous stupidity of the human race (in the long run, collectively) to science (when there's plenty more in other fields), this is just more part of human arrogance that has brought us other myopic spectacular fuck ups as:
Earth is the center of universe (at pain of death, no less); We can introduce a new predatory species to a virgin ecosystem to control an existing pest; Aliens can't possibly exist as we are clearly the best God could create; We understand all physics and all reality and therefore even if the incredible impossibility of aliens existing were true, they couldn't possible ever visit us from other solar systems because we can't figure out how their doing so could be consistent with the equations of physics we devised; ancient people's are so incredibly primitive compared to us today, they must of only had inferior methods of almost everything; despite being so inferior to us, they created multiple megalithic monuments (primitively, of course), because we are clearly so superior to anything else that could possibly exist there could never have been other human or non-human civilizations on this planet doing stuff we still can't...
A disappointing collectivist conformity on hyperdrip into the mainline of what should be global creative scientific endeavor on this planet is instead a monument to our collective stupidity, ignorance and anthropocentric, self aggrandizing myopia.
Hopefully that self-limiting arrogance is a genetic trait we will soon evolve out of....as long as people keep reproducing!!!
> it's so stupid to assume they were junk.
They didn't. "Everyone Thought X but actually Y" is popular science speak for "nobody thought X but we want to talk about Y so let's pretend for a moment."
> A disappointing collectivist conformity
Clickbait sucks, but I wouldn't call it collectivist, the opposite if anything.
> self-limiting arrogance is a genetic trait we will soon evolve out of
Eugenics? Really? Over this?
Check out Homeobox Proteins.
From what I can tell, ENCODE project collected a ton of data suggesting that large regions of DNA which are not under functional selection (to the extent that we can measure that) are actively transcribed. They released some press and papers suggesting this meant that "junk DNA was not actually junk", which led Eddy to have a rage fit and propose an experiment to support his beliefs.
From what I can tell, we still don't have a great explanation for why large regions of DNA that are not under apparent functional selection are constantly being transcribed and what evolutionary impact that has on organisms. Personally I think Eddy greatly overplayed his claims, depending on some historical details in genome analysis that probably are dated and missing critical new biology, but honestly, these are areas where the theories and data are so ambigious, you can construct any number of narratives explaining the observed results.
We're just scratching the surface of the complexity encoded into DNA and RNA.
It's not the base pairs that are expressed, all the stuff not expressed is encoding information as well. DNA, like proteins, encodes information in the way it folds itself around histones. DNA can't be expressed if it's still in a compact state!
So it look like RNA is similar. The noncoding sections are part of the system that regulates how the encoding parts are encoded.
It seems like that would be a smart strategy for evolution instead of permantely deleting something.
Is it fewer then that due to what we know about variance in codon sequence alignment?
Does protein coding viability further limit the viable combinations?
Anyways, there's been an explosion of different classes of RNA in the past decade or so. This has been driven by new techniques in RNA sequencing technology that allow us to detect and sequence RNA in a more unbiased and high-throughput way. What we saw was a huge number and variety of RNA molecules in cells that don't look like they encode any protein. So, this fundamentally breaks that assumption about RNA's role as "just" a messenger.
The best characterized class of these weird new non-coding RNA's is probably micro-RNA. They're very short stretches of non-protein-coding RNA, and it seems that they bind to other sequences of RNA and prevent their translation to proteins. So, RNA has at least one layer of self-regulation. Then we see long non-coding RNA. They can act as "sponges" or buffers of microRNA by preferentially binding to miRNA, preventing the micro-RNA's interaction with their normal protein coding RNA targets. So, there's another layer: long non-coding RNA buffers microRNA which inhibits translation of messenger RNA. Further the long RNA can also condensate into these structures that are similar to droplets of oil in water. They're transitory structures that form and dissolve then reform quickly and repeatedly. What they do is still a bit vaguely understood but they seem to bring together very weakly interacting proteins and RNA in concentrations that wouldn't be possible just by diffusion within the cell. So, there's another layer of regulation: long coding RNAs form condensates to that allow interactions between proteins that wouldn't happen otherwise.
All of this is complicated by the fact that these things have other weird properties. They aren't expressed very frequently, so they're hard to detect. They're not very well conserved evolutionarily, i.e. their sequences diverge rapidly between species. They don't really have fixed structures, they're more just like floppy, sticky noodles. This would typically indicate they're not functional or at least non-essential. How could this be important? It's an RNA that doesn't make a protein, isn't very abundant, has no defined shape, and evolution doesn't seem to care much about the details of its sequence.
*But*, as this paper shows, they're absolutely essential for cellular function. If you take them out of cells, the cells die.
So, all that to say that the idea of biology as working like a little computer; just a series of linear information transmission steps, is probably rather misleading in many cases. Instead it's a tangled mess of weak interactions that depends on subtle biochemical effects like condensation. It's noisy and imprecise at the molecular level, but all the self-interacting layers of regulation and interaction somehow give rise to remarkably precise and adaptive responses at the tissue and organismal level.
To me, thats much more amazing than a designer who builds life like a really complicated lego kit. In fact it’s almost insulting to imply that God couldn’t create our world through evolution. Evolution is so much more beautiful and complex than the (easily comprehensible) image of a guy tinkering in a celestial garage.
https://gethisword.com/evidence.html
In His Word, God says He created us in an intimate way like a potter forms clay. A form He takes later when Jesus Christ lives among us to save us. He created us over six days. He also set in motion laws that allow things to further optimize within their environments. He allowed similar algorithms (eg GA’s) to be used to solve problems for us. God is really good to us.
That’s just the start, though. Every worldview has a foundation. His involves objective morality, a design that benefits us, and love for each other. All things were to be done that way. He blessed nations that did. Those who did the opposite increased in strife, violence, and sickness. Most sinful nations perished while God’s nation, Israel, was re-created out of thin air as prophesied.
Adaptations Darwin noticed were too tiny to cover the universe’s and life’s design and complexity. The normal rules of science don’t allow huge leaps from tiny mechanisms to massive systems. Yet, people from sinful backgrounds didn’t want God to be real because they’d face the consequences of their sins. They needed theories that let them be gods, in control. So, they traded both divine revelation and scientific observations for fanciful speculation with zero proof.
Their atheist religion included fifty to a hundred precise laws that just spontaneously emerge, a universe with 100% reliability by accident, kinds turning to other kinds millions of times with virtually no transitional forms, life just spontaneously emerging (eg Cambrian period) after extinctions, and making excuses for why we never observe this in over a billion animals today.
Those believing this took over academia, media, and film. They force the views on all in their sphere with opposite views usually censored, even with evidence. The new worldview, that we’re just chemical configurations in a meaningless universe with death a helpful tool of progress, gave rise to horrors. Racial superiority, eugenics, forced sterilization, and genocide are directly justifiable by evolution theory. By subjectivism, any evil under the sun can be justified since morality is perceived to be imaginary.
Sure enough, the culture justified more evil over time. How they entertain themselves now, music or movies, is people being vicious, treating others like objects, using them for sex/money, theft, rape, murder, and recently glorifying the name of Satan. God’s Word predicted these specific things would increase which means they’re further evidence it’s true. Not only bad science, the atheist, liberal, evolutionary worldview takes us into moral depravity that thoroughly damages us.
This should not be tolerated by scientists. Within science, it is opposite of the scientific method that says to discard theories consistently disproven by observed data. They must build on observations. Outside of science, it ignores all the evidence of God’s Word being a superior model with better results. We must build on the truth with love which is a worldview that God blesses and more people benefit from.
It's like trying to repair a sinking ship at sea without understanding how the planks and caulking displace water. Sure you might patch it temporarily, and might even keep it afloat, but what other problems are you creating that you literally don't know anything about...
It leaves you with limited understanding of the mechanism, it's efficacy across different populations, the circumstances in which it fails, how bad those failures could get, or how to improve the product in any way whatsoever.
I know what I'd choose givin the option of avoiding sinking, and possibly dealing with unknown and probably minor consequences later; or dealing with a potentially deadly sinking now, and avoiding unknown (and probably minor) consequences later.
Sad.
https://en.m.wikipedia.org/wiki/Central_dogma_of_molecular_b...
Also, "debunked" implies something was proven to be false, which is not the case with the central dogma.