I've never heard of a policy like that for physicians and doubt it's common for paramedics. I work in an ICU and a typical day involves a death or resuscitation. We would run out of staff with that policy.
Maybe it's different in the US where ambulances cost money, but here in Germany the typical paramedic will see a wide variety of cases, with the vast majority of patients surviving the encounter. Giving your paramedic a day off after witnessing a death wouldn't break the bank. In the ICU or emergency room it would be a different story.
Ambulances cost money everywhere, it's just a matter of who is paying. Do we think paramedics in Germany are more susceptible to PTSD when patients die than ICU or ER staff, or paramedics anywhere?
Not in the sense that matters here: the caller doesn't pay (unless the call is frivolous), leading to more calls that are preemptive, overly cautious or for non-live-threatening cases. That behind the scenes people and equipment are paid for and a whole structure to do that exists isn't really relevant here
> Do we think paramedics in Germany are more susceptible to PTSD
No, we think that there are far more paramedics than ICU or ER staff, and helping them in small ways is pretty easy. For ICU and ER staff you would obviously need other measures, like staffing those places with people less likely to get PTSD or giving them regular counseling by a staff therapist (I don't know how this is actually handled, just that the problem is very different than the issue of paramedics)
I might have misremembered that, but remember hearing the story. Now that I think about it I think that policy was applied only after unsuccessful CPR attempts.
Some non-protein coding DNA produces RNA which serves a purpose. We also know that there are large areas of non-coding DNA which are very important for transcriptional regulation.
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.
My understanding of it is that in eukaryotes the genome is folded up like the pages of a book and that one function of non-coding DNA is control of the opening up of these "pages" which in turn plays a major role. You are not just looking at RNAs being expressed but also sections of DNA that those RNAs bind to, pieces that bind to each other to keep pages shut, probably things like the hinges and springs in a pop-up book.
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.
The extremaphiles that survive radiation are both tetraploid and keep their dna packed tight when not coding proteins or whatnot. Packed DNA can spontaneously re-fuse broken chemical bonds to the original site rather than tearing or picking up new fragments.
> But it remains true that there are large amounts of non-coding junk DNA which is under no selection pressure
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.
It's benign in the tested environment. You can't really test every possible environment (diet, climate, etc), so it seems roughly comparable to the halting problem; Does there exist a micro-deletion that in some environment causes this life to halt? It's unsolvable at DNA scale.
"Benign" in a clinical genetics context means "the variant is not linked to observed phenotype in patients". Patient lives their life without disability, reproduces without issue.
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.
Yeah I feel pretty incredulous about this too. Surely you would want to see a few hundred generations reproducing with the change before you could begin to say with any confidence that it might not have an effect.
>> non-coding junk DNA which is under no selection pressure
> "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.
> There are other large sections where it can disappear and nothing of consequence seems to happen.
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.
I don't think you have to argue for junk DNA to state that the article in question fails utterly to explain the findings except by way of not being the straw-man "junk".
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.
I don't have an qualms with the research. I think it was shared on HN because of the never-ending articles about "it's not junk after all" which is what I was reacting to. The linked press release uses this term, but the original study does not. I agree with your points.
That seems like a fallacy to claim to know that there is in fact junk dna.
To know that: you need to iterate over every possible function for a section of dna could have and test against that.
I get the skepticism. There have been a lot of surprising revelations in biology and I don't think anyone would argue we have every angle nailed down. However, the idea that some DNA is genuinely “junk” is based on more than a hunch. It’s from looking at patterns across species. If a sequence really mattered, then changing it should cause a problem. That would put pressure on the sequence to stay the same, generation after generation. Yet we see big stretches of DNA mutating freely, at rates that exactly match what would be expected from accumulation of random copying errors. That suggests these sequences aren’t under selection for any important function.
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.
The absence of clear selection pressure on certain RNA pairs doesn’t prove they lack function; many biological roles are subtle, context-dependent, or involve redundancy, making them difficult to detect with current methods. Freely mutating sequences could still influence genome architecture, gene regulation, or adaptation in ways not yet understood, as seen with elements like noncoding RNAs and transposable elements previously dismissed as “junk.” Additionally, these sequences may serve functions over long evolutionary or environmental time horizons, becoming critical under future conditions we cannot yet predict, underscoring the importance of not prematurely dismissing them.
I'm not suggesting that these sequences can "look forward" in time. However, consider that mutations are constantly occurring. These mutations shouldn't be dismissed as "junk" simply because they seem unnecessary now. In the future, they could become essential.
Over long evolutionary or environmental timeframes, these sequences may take on important functions, potentially becoming critical under conditions we can't currently foresee.
If such a mutation occurs, that sequence would no longer be junk. Until and unless it does happen, it's still junk. But it's silly to get hung up on the sequence, or on the word "junk", based on such a slim chance. What are you trying to prove here?
The weird thing is that some of these lncRNA don’t seem to be under super strong selection pressure, at least at the level of individual nucleotides. Their promoter regions are conserved, which indicates that the cell really does need to produce them, but it doesn’t seem to care much the actual sequence. Very strange.
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.
I think we’re basically on the same page. As you note, a conserved promoter without strong sequence conservation elsewhere suggests functions that might be more structural or regulatory. Still, it’s also true that some (actually many) non-coding regions show no evidence of selection and appear to evolve neutrally.
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.
Great overview. Worth adding some population genetics: Multicellular organisms typically have small effective population sizes and reproduce slowly in comparison to bacteria. Selection has a hard time “getting a grip” on variants with very weak effects on fitness. Drift becomes much more important.
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.
Sometimes with lncrnas the structure is what is more important than sequence. You can have two lncrna with different sequence but the same kmer structure. This makes logical sense as while proteins often bind to specific sequence the reasons for that are merely structural. In protein you can also have conservative missense mutations that are tolerated as binding affinities may not have changed swapping out an amino acid residue for another with the same charge or polar properties.
> Yet we see big stretches of DNA mutating freely, at rates that exactly match what would be expected from accumulation of random copying errors.
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.
Most of the genome is non protein coding. Some is functional, most simply is not functional in any way. It is just empty space.
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.
As said below, the sequence of the junk DNA does seem to mutate a lot faster than parts of the DNA which is known not to be junk, heavily suggesting that at least the exact sequence is not so important.
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.
I read once (maybe in a Dawkins book) that large gaps also help preserve genes during sexual reproduction when chromosome crossover happens. Basically if the crossover point happens in the middle of a gene, that gene doesn’t survive the meiosis… having large gaps increases the odds that crossover happens in junk DNA. I’m not sure how true/oversimplified this is though.
What I read was from “The Selfish Gene”, I went and dug up the section:
> 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.
Funny, I read that same section two weeks ago. Dawkins’ definition is not what geneticists typical consider a gene. His “gene” is more like what I would call a haplotype in that he divorces “gene” from “protein-coding” region. But he has a good point and I like this section. But he wrote it in the genetic dark ages and we now know quite precisely where and how often recombinations occurs, and for how long haplotypes are preserved as a function of generation numbers.
Highly recommend David Reich’s book for are good overview of the math of recombination in humans.
Thanks for the recommendation! I’ll have to check it out.
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.)
I would say that, on balance, one must prove DNA to be not-junk.
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.
Teleost fish that you and I would have a hard time telling apart, can have a genome sizes that range from 0.5 billion basepairs to 50 billion base pairs. It would be difficult to explain this huge range as due to selection acting at a fine grain on 49.5 billion nucleotides.
This is just pure assumption from my part, I know nothing about this. But extrapolating from your point:
> 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.
I understand that you say “junk” dna in the context of the individual, but I’m curious if there could still be some selection pressure on this “junk”? For instance, I can imagine that “junk” which has more variety in it may generally result in more useful mutations, and this could put pressure on our “junk” to have high entropy, almost providing a source of randomness. I know very little about the field though — am i totally off base?
Are we completely sure about that? In my mind it could just be that we don't understand it well enough yet. I mean, junk to us maybe. Nature tends to produce pretty optimal designs from my experience.
Nature tends to select things that are just good enough. If nature was optimal, we wouldn't have appendices that need removal, a backward retina, or spines optimized for horizontal placement.
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.
Could, but it also could be an indicator of "we don't really understand biology yet".
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.
Any reading on the topic you could point me to? Whenever I head about vestigial DNA, I’m reminded of the preserved wetlands which forced the roads to arc the long way around it. And in so doing, structurally affected traffic despite no cars ever going inside its bounds.
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”?
It's just that very often when we judge like that, it later turns out we might have been mistaken. The appendix is a perfect example.
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.
Selection pressure can be measured. If a big chunk of DNA is missing from a third of a population with no apparent ill effects, the onus is on you to show that it was somehow important. Of course there is plenty of non-coding DNA which is under selection pressure and therefore does something important, but everyone has known this for decades.
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.
>the onus is on you to show that it was somehow important
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.
>In this case that hypothesis is "all other DNA/RNA is junk",
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' ".
It's like this: now that full-genome sequencing is getting pretty cheap and common, you can tell how string the selection pressure is on a chunk of DNA just by looking at frequencies of variants. If it turns out there are very few variants, you can be confident the chunk is doing something, even if you don't know what. If the variation looks like random drift, you can be pretty confident it is.
No, you seem to only have a casual/superficial understanding of the field.
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.
As others and I have mentioned above, there are absolutely parts of the genome that are functional despite being non-coding. There is no debate about this. You have shared links and arguments emphasizing that there is function in these parts. However, you have not addressed the fact that there are large stretches of DNA that are not conserved across species, show no differential selection pressure compared to what would be expected from random genetic drift, and that there are hugely varying sizes of genome between species.
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.
You're refuting a strawman. The junk DNA claim is not, and as far as I can see never had been, that all non-coding DNA is junk. It's that most of our genome -- around 90% -- is junk[1][2]. But since the genome is over 98% non-coding, that implies that something like 8% is functional non-coding DNA, which is several times the amount of coding DNA. Finding small amounts of additional functional non-coding DNA does not significantly challenge this[3].
I don't even have the words to express how little I care if companies serve me targeted ads with cookies. On the other hand I absolutely despise what the average visit to website with a cookie banner has become.
Blame the companies, not the regulations. A significant part of their reasoning behind byzantine stalking permissions banners is that they are deliberately inconveniencing people like you who don't care, so you can be weaponised against those of us who do in discussions about the regulations and related privacy matters.
The immediate allure of hollow-core fibers is that light travels through the air inside them at 300,000 km-per-second, 50 percent faster than the 200,000 km-per-second in solid glass, cutting latency in communications. Last year, euNetworks installed the world’s first commercial hollow-core cable from Lumenisity, a commercial spinoff of Southampton, to carry traffic to the London Stock Exchange. This year, Comcast installed a 40-km hybrid cable, including both hollow-core and solid-core fiber, in Philadelphia, the first in North America. Hollow-core fiber also looks good for delivering high laser power over longer distances for precision machining and other applications.
Yes, funnily enough Microsofts reason was not HFT but AI. Essentially inter-datacentre training is limited by latency between the datacentres.
Generally they want to build the datacentres close to metro areas, by using hollow core fibre the radius of where to place the data centres has essentially increased by 3/2. This significantly reduces land acquisition costs, and supposedly MS has already made back the acquisition cost for Lumenisity, through those savings.
That feels somewhat implausible. I assume a Microsoft sized data center starts at over $100 million. Moving the footprint X miles away might be cheaper, but is probably a drop in the bucket given everything else required for a build out. I would further assume that they were already some distance away from the top tier expensive real estate to accommodate the size of the facility.
Its reality. Its generally about site and infra access, including power and fiber paths. The bigger providers (eg AWS) simply dont have more feasible sites that are within a few ms of the existing region DCs. Expect to see more infrastructure like “local zones” or AZs that are tens of ms away from the rest of the region.
By definition, it does, because the maximum speed is qualified by "the speed of light in a vacuum", so the speed of light [in other media] is simply a function of how much the medium slows it down, yet it is still the speed of light. Funny how that works!
Anyone who is smart enough to use this weird triple shift key shortcut is intelligent enough to preload a different site in another tab and use the close tab shortcut. I would guess there is almost complete venn diagram overlap between people who can learn this weird shortcut and people who can deal with this threat in any other way using normal browser functions.
It would be interesting to run an experiment to see how long we could keep a mouse alive using the results of all these mouse-positive trials, treating each disease as it crops up.
That white hose you see coming off the back of it is the drive line which passes out the chest and connects to an external battery. It's not a normal life with one of these in place, a heart transplant would be vastly preferable.
