Normally it means "poor quality" though. I think "junk DNA" is more analogous to "dead code". Not all code labeled "dead" is actually unreachable/unused.
Everyone doing biology professionally already knows the non-coding DNA has function. It’s only logical since we know that resource-intensive mechanisms don’t survive the evolutionary pressure if there’s no benefit for them to exist. So it’d be wasteful to replicate 98% of DNA if it’s not functional. Keep in mind it’s not only replicated, there’s error-correction as well.
it's wasteful to replicate non-functional DNA, yet there are organisms whose genomes are 10X-100X larger than any others (literally ten copies of a genome), and they do just fine (https://en.wikipedia.org/wiki/Paris_japonica). The cost of DNA replication isn't that strong a functional selection afaict.
Probably not in the context of the example I gave; that's more likely to just be a totally random genome duplication which will eventually be functionally selected away.
I'm not conflating anything. Those details are scientifically conflated (IE, they are functionally related) in a very interesting way. For exmaple, new genes probably arise from gene or genome duplications.
Yes, I know that. It's unclear what aspects of those duplications are "functional but not coding for genes, enhancers, promotors, or other well-known and understood coding and regulator elements", and which are "functional because if you remove it the organism dies but we can't explain what the cause is".
Everything in my terminology is entirely correct within the current mainstream understanding and it encapsulates much of the ongoing confusion about what "role" non-coding functional elements play, and how they play it.
I am of the opinion that nearly everybody in this field is overly dogmatic in their views of how genomes work at the macro scale, and that these squabbles demonstrate that clearly.
For more context, please understand that as a researcher in this field, much of what I say may not make sense to casual readers. I decided it's better to think about minimal organisms, than ones that have 500 copies of the ribosome (http://citeseerx.ist.psu.edu/viewdoc/download?rep=rep1&type=...)
And yet we probably don't know why they have so many copies. Maybe it's a crude method of regulating the ratio of activation on genes. If a few genes are either on or off, and you want to have ratios other than 1:0 1:1 or 0:1, maybe independently activating N of the M copies can achieve that. Just speculating as to how multiple copies might be useful.
You can't prove that they are "extra copies" until you understand pretty much everything about them and their interactions with everything else.
While I agree in principle, it does look like in most cases, these 100X large genomes are just due to random events that haven't been selected away. Often, what you see looking at evolutionary processes at a point in time, you want to find a "reason for why it's this way", when the reason is "it was random chance". Compare deinococcus radiodurans, where there's a whole mechanism for exploiting multiple copies of the genome. Plants wiht 10X genomes don't seem to exploit that, afaict.
that's now how evolution works. evolution tolerates enormous amounts of things that don't 'give advantage', and 'advantage' is a fairly subjective term anyway. Any number of possible events could have occurred to lead to the scenario we see. Population bottlenecks often lead to strange outcomes.
It’s always random chance. What’s non-random is why it’s kept in the genome. I’m no plant expert, but genome duplications could be linked to increased fitness due to amount of resulting protein product, right?
If the organism is pressured, the non-coding DNA slowly fades. There are some parasitic organisms (eg Nasuia deltocephalinicola) that have highly compacted DNA: no introns, no regulatory regions, no transposable elements and even overlapping genes.
Early text: Details evidence that term is misguided.
Late text: Continues to use early term so as to provide a consistent interface to readers. Might use 'scare quotes' if term is particularly egregious but still conserves familiarity of terminology.
What would you have them do instead? Naming stuff is hard. The authors get their point across quite nicely without also trying to coin more terminology.
Famously, people with multiple copies of GGGGCC in a particular section of their non-coding DNA are prone to horrible neurodegenerative diseases including ALS (shudder).
Most genetic variants associated with common diseases fall in non-coding DNA areas, previously thought to be junk DNA.
Many of these non-coding areas are actually enhancer elements. These elements produce enhancer RNA, previously thought to be noise, and regulate distant genes thanks to chromosome conformation. Chromosome conformation means DNA folds in complex 3D patterns.
The interplay between chromosome conformation, enhancer RNA, gene expression and disease variants is very complex and interesting [1,2].
I know some startups trying to regulate genes by targeting enhancer elements. The field is very promising, but a big roadblock seems to be to deliver compounds to the right cell type.
Junk DNA was always contentious because there was evidence of conservation in these areas. In other words, evolution was selecting against mutations in some junk DNA regions. My impression is that junk DNA fell quickly out of favor once the ENCODE Project started to publish large scale epigenetics data in the early 2010s.
The fact that enhancers can be transcribed is quite interesting. I’m not sure what’s the function of these transcripts though. It seems like the transcription is terminated prematurely once RNA pol realizes it’s not a functional gene.
There's a lot of literature on this, but you are quite right as there are tons of open questions. Some enhancer RNAs are non-functional. Others seem to help stabilizing chromosome contacts. Some do seem to encode secondary structures, so they are probably functional ncRNAs.
Irrespective of this, enhancer RNA transcription is very useful to track active regulatory regions and to perform QTL studies.
For starters, junk DNA is a fuzzy term. I would never include regulatory regions or introns in junk DNA, just non-coding. To me, junk are tranposons and friends, or pseudogenes: they rarely have any purpose, and sometime they cause troubles.
I remember talking to my colleagues about 15 years ago about trying to do research on some noncoding polymorphisms and was ridiculed. The basic response was something along the lines of "those are noncoding, why would you look at those?" as if I was an idiot who didn't understand current genetics.
It's been long ago enough that I don't remember all the details, but my perspective was that it was naive and arrogant to assume we had a good handle on everything about DNA, especially then as it was all new, and there was evidence then that a lot of the noncoding DNA had function.
Dogmatic attitudes are surprisingly prevalent in academics. There's definitely a weird hubris accompanying published findings that goes something like peer reviewed -> established fact as if the point of academics isn't to understand things but to score points like on a test. Some skepticism about certain things seems warranted but other times there's really nothing but overly simplistic models that were really never evaluated to begin with. I wish there was more awareness of the topography of uncertainty in research findings.
Having a list of proteins (coding DNA) does nothing to tell an organism how to combine those proteins to form working systems.
It's like claiming that the parts list in an assembly manual is the only information of importance. And the step-by-step instructions are junk, because they don't describe a useful part in the box.
Did we think that the whole organism just self-assembles once it makes the tens of thousands of individual parts described in coding DNA?
"Junk DNA" was a terrible terrible phrase to begin with.
While an interesting thought experiment, no one is proposing that you will get self-assembly of an organism by expressing 10,000 genes. We really don't know what the beginning steps of this process were - since it only happened once (or however many times life arose). Once an organism was made, now it can just express whatever proteins it currently needs, based on lifecycle/nutrients/metabolic requirements/etc.
Natural selection doesn't care about what looks pretty, only that it works. A modern operating system is millions of lines of code. Do you think it is possible that some of the code are no longer used but nobody dares remove it?
That'd be the case if a conscious entity was not daring to remove code.
An evolutionary process, on the other hand, doesn't fear removing random sections so their continued presence indicates the "junk" must (somehow) be important to the organism's fitness.
Imagine a big machine run by paper tape. On the tape are two possible holes. Punch one and feed it in, the machine makes a man. Punch the other, it makes a mouse.
Does the tape 'encode' the essence of 'human being'? (or even 'mouse'?) Of course not.
The machine is a vital part of the equation. Likewise, dna in a jar is just a molecule. It has to have a cell, evolved over a billion years, ready to make something of it.
Yes you're right, we know that DNA is inert and used as a storage device by an organism.
What we don't know is how an organism with no intelligence (cell), could develop code (DNA), archive it, rehydrate it and then parse and copy it like someone with intelligence.
Without getting too deep into it, it's just not convincing anymore to appeal to vast amounts of time and random chance to do something which is fundamentally within the realms of engineering.
Sure we do. It's littered with history, fragments from all over. And organisms today are more complex than organisms of the past, some of which still have remnants existing. So many stages of development as examples. There's no magic to it.
You're entitled to your opinion, but what you're suggesting is wrong. What you've said are some observations made and some interpretations based on evidence gathered but none of it concludes that cellular organisms invented DNA, that suggestion is still stuck in a chicken vs egg scenario.
The fact is, we don't know how these systems could have created themselves or been created abiogenesis. There are wildly different theories, but it's far from a closed case.
I used to think the same thing as you because that's all I was taught to think, but perhaps if you looked at what synthetic chemists think about abiogenesis you may find it interesting / informative to see what they have to say about the challenges involved in it. An interview with a synthetic organic chemist on the topic: youtube.com/watch?v=r4sP1E1Jd_Y
Since I learned of this so-called Junk DNA, I assumed that one function of it might be to dilute the density of critical DNA sequences.
In other words, if every base pair matters, then DNA damage from, say, ionizing radiation is more likely to be a problem than if only 1/100 base pairs matter.
Hypothetically, let's suppose risk of damage correlates with cross sectional area of DNA. It's conceivable that scaling up length with less critical segments reduces risk faster than the increasing cross section increases it.
It's an interesting idea from the OP. I'm basically imagining a box full of rope and someone is poking the box with a stick. The length of rope that can fit in the box increases faster than the box's cross section.
See "On the Immortality of Television Sets: “Function” in the Human Genome According to the Evolution-Free Gospel of ENCODE" for an entertaining (and peer-reviewed) background on this terminology.
Non-coding DNA before a protein coding sequence has a very important function obvious to any programmer:
It is a large section of pattern-matching "if"s.
Depending on the current state of the cell, various proteins will bind to the DNA in these places to either increase or restrict production of this specific protein. This allows multi-stage configuration of cellular protein production.
If this won't be the case, the cell will produce an equal amount of all coded proteins, which would be silly.
Source: something I learned while helping with coding for a paper in biology.
At uni we were told junk DNA is repository of new/old genes for evolution. Old unused proteins may get activated by mutation, and reporpused for new function.
To me the hole notion of junk DNA seamed wrong or even ludicrous the first time I heard of it.
I have a hard time understanding that anyone with a proper education in the field would ever believe the junk dna thesis.
Could it be that it has something to do with me being educated in computers before being educated in biology?
The analogy’s a person with computer knowledge would use might make it hard to see these things as junk.
I don't think this article gives the pro-"Junk DNA" arguments fair treatment.
Check out Larry Moran's blog [1, 2] if you want to to hear the other side of the story. He maintains that most of the human genome IS junk, and I find his arguments compelling.
Any time I read about how some part of the body has no function, I try to remember that our understanding of the body is superficial at best, it was only a 100 years ago when getting your blood sucked by leeches was the standard of care for many conditions. Mother's milk was supposed to contain useless and indigestble substances till it turns out they were important for developing the baby's gut microbiota. Entire organs such as the thymus were considered useless and then we began to understand the critical role they play in our immune systems. Once we consider that even critical muscles waste and atrophy unless used, we have to understand that whatever we retain in our bodies must be absolutely critical to its long-term survival, and there is no such thing as a "junk" component.
That reminds me of both tonsils and the appendix - two body parts that are often referred to as "useless" even though they probably do some function we're just not aware of.
As for appendix, it seems to be home for bacteria that can cause dementia but are otherwise useful in the gut. I don't know if that's actually its purpose, but if so, it seems pretty important.
The appendix is vestigial, not useless. It's fair to say it's vestigial, because you can remove it from large numbers of people and they don't die, which is very different from organs like the liver, heart, or lungs.
.... you know that leeches are used in modern medicine, right? Not for bloodletting, but many of the contexts that leeches were used for have enough overlap with bloodletting that it's actually best to assume that folks actually did use leeches to good effect.
The core of this ongoing debate is mainly about some regions, like Alu, which appear to truly have no function, and have little to no functional effect. I think scientists could still make a good faith experimental effort at attempting to salvage this idea, see Eddy's proposal about a "neutral genome" here: https://www.cell.com/current-biology/comments/S0960-9822(13)...
The fairest way to describe it is that scientists continually find that more and more DNA that was neglected as having zero functional (no observable, measurable, directed activity that is under evolutionary selection pressure) effect, does indeed affect the fitness of organisms in ways that are not accomodated by existing theories of gene expression or regulation. It seems unlikely, however, that we will ever truly be able to point to every single base pair in teh genome and say "it's under functional pressure", and if that's the case, it's easy to make the argument that some of it is "junk".
However, complex information processing systems like life don't really fall into simple classification, "junk" is really a subjective term, we should focus instead of measurable scientific phenomena like fitness.
Yes, the main problem with leeches in historical use was that medical theory believed disease was caused by a miasma and that drawing bad blood would cure the cause.
Today, we still use leeches but only for those cases where they can provably affect the cause.
that's not really correct. we have a narrative for why leeches work, but it's not really a "provably affect the cause" sort of thing. We just know they eat dead tissue and suppress immune responses.
Non-coding DNA may also affect its shape. Most of the time when not in mitosis, DNA appears to be jumbled. Thatbshape might be intentional for sone yet unknown reasons.
The reason it's called 'junk' is because they don't know what it's there for yet. (Same reason archeologists find so many 'temples'. And consciousness is just a 'side-effect' of physics and chemistry.)
Computer programs require both code and space for variables and also require 'defines' that don't show up as actual variables or actual code but tell both code and variables what their working values need to be.
Or maybe to put it in another way, in terms of usefulness, is that the 'junk DNA' holds the same significance as the programming header files do. Maybe we should be calling those data sequences of DNA as 'junk.h'.
I venture to say that maybe only 0.1% of the stuff we call 'Junk DNA' (or even none of it) is irrelevant.
“Some of it is essential for life, some seems useless, and some has its own agenda.”
It’s like you have a bookshelf filled with books. Some books you haven’t read, some were gifts, some were acquired, some you didn’t finish and some book you will read over and over again. All of them were kept for some reason.
I don’t believe nature would create something that’s completely useless. I just know that often I fail to see what the use might be.
62 comments
[ 6.0 ms ] story [ 142 ms ] threadRest of the article: continues to use the term "Junk DNA".
Everything in my terminology is entirely correct within the current mainstream understanding and it encapsulates much of the ongoing confusion about what "role" non-coding functional elements play, and how they play it.
See http://cryptogenomicon.org/encode-says-what.html and https://www.cell.com/current-biology/comments/S0960-9822(13)... for the strongest arguments against ENCODE's more wide definition of functional elements, as well as https://www.pnas.org/content/110/14/5294 and https://www.mun.ca/biology/scarr/MGA2_02-10.html
I am of the opinion that nearly everybody in this field is overly dogmatic in their views of how genomes work at the macro scale, and that these squabbles demonstrate that clearly.
For more context, please understand that as a researcher in this field, much of what I say may not make sense to casual readers. I decided it's better to think about minimal organisms, than ones that have 500 copies of the ribosome (http://citeseerx.ist.psu.edu/viewdoc/download?rep=rep1&type=...)
You can't prove that they are "extra copies" until you understand pretty much everything about them and their interactions with everything else.
Early text: Details evidence that term is misguided.
Late text: Continues to use early term so as to provide a consistent interface to readers. Might use 'scare quotes' if term is particularly egregious but still conserves familiarity of terminology.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202986/
Many of these non-coding areas are actually enhancer elements. These elements produce enhancer RNA, previously thought to be noise, and regulate distant genes thanks to chromosome conformation. Chromosome conformation means DNA folds in complex 3D patterns.
The interplay between chromosome conformation, enhancer RNA, gene expression and disease variants is very complex and interesting [1,2].
I know some startups trying to regulate genes by targeting enhancer elements. The field is very promising, but a big roadblock seems to be to deliver compounds to the right cell type.
Junk DNA was always contentious because there was evidence of conservation in these areas. In other words, evolution was selecting against mutations in some junk DNA regions. My impression is that junk DNA fell quickly out of favor once the ENCODE Project started to publish large scale epigenetics data in the early 2010s.
[1] https://genomebiology.biomedcentral.com/articles/10.1186/s13...
[2] https://www.nature.com/articles/nature13138
Irrespective of this, enhancer RNA transcription is very useful to track active regulatory regions and to perform QTL studies.
It's been long ago enough that I don't remember all the details, but my perspective was that it was naive and arrogant to assume we had a good handle on everything about DNA, especially then as it was all new, and there was evidence then that a lot of the noncoding DNA had function.
Dogmatic attitudes are surprisingly prevalent in academics. There's definitely a weird hubris accompanying published findings that goes something like peer reviewed -> established fact as if the point of academics isn't to understand things but to score points like on a test. Some skepticism about certain things seems warranted but other times there's really nothing but overly simplistic models that were really never evaluated to begin with. I wish there was more awareness of the topography of uncertainty in research findings.
https://en.m.wikipedia.org/wiki/Planck%27s_principle
“Science progresses one funeral at a time.”
Having a list of proteins (coding DNA) does nothing to tell an organism how to combine those proteins to form working systems.
It's like claiming that the parts list in an assembly manual is the only information of importance. And the step-by-step instructions are junk, because they don't describe a useful part in the box.
Did we think that the whole organism just self-assembles once it makes the tens of thousands of individual parts described in coding DNA?
"Junk DNA" was a terrible terrible phrase to begin with.
Disclaimer: I believe in a creator. (https://www.jw.org/en/bible-teachings/science/)
An evolutionary process, on the other hand, doesn't fear removing random sections so their continued presence indicates the "junk" must (somehow) be important to the organism's fitness.
Imagine a big machine run by paper tape. On the tape are two possible holes. Punch one and feed it in, the machine makes a man. Punch the other, it makes a mouse.
Does the tape 'encode' the essence of 'human being'? (or even 'mouse'?) Of course not.
The machine is a vital part of the equation. Likewise, dna in a jar is just a molecule. It has to have a cell, evolved over a billion years, ready to make something of it.
So no self-assembly, no magic in the DNA.
What we don't know is how an organism with no intelligence (cell), could develop code (DNA), archive it, rehydrate it and then parse and copy it like someone with intelligence.
Without getting too deep into it, it's just not convincing anymore to appeal to vast amounts of time and random chance to do something which is fundamentally within the realms of engineering.
The fact is, we don't know how these systems could have created themselves or been created abiogenesis. There are wildly different theories, but it's far from a closed case.
I used to think the same thing as you because that's all I was taught to think, but perhaps if you looked at what synthetic chemists think about abiogenesis you may find it interesting / informative to see what they have to say about the challenges involved in it. An interview with a synthetic organic chemist on the topic: youtube.com/watch?v=r4sP1E1Jd_Y
https://jacquesmattheij.com/junk-dna-no-way/
with the newly found insights. Still: No Way. Just not-yet-understood-DNA.
In other words, if every base pair matters, then DNA damage from, say, ionizing radiation is more likely to be a problem than if only 1/100 base pairs matter.
It's an interesting idea from the OP. I'm basically imagining a box full of rope and someone is poking the box with a stick. The length of rope that can fit in the box increases faster than the box's cross section.
https://academic.oup.com/gbe/article/5/3/578/583411
Depending on the current state of the cell, various proteins will bind to the DNA in these places to either increase or restrict production of this specific protein. This allows multi-stage configuration of cellular protein production.
If this won't be the case, the cell will produce an equal amount of all coded proteins, which would be silly.
Source: something I learned while helping with coding for a paper in biology.
I have a hard time understanding that anyone with a proper education in the field would ever believe the junk dna thesis.
Could it be that it has something to do with me being educated in computers before being educated in biology? The analogy’s a person with computer knowledge would use might make it hard to see these things as junk.
Check out Larry Moran's blog [1, 2] if you want to to hear the other side of the story. He maintains that most of the human genome IS junk, and I find his arguments compelling.
[1] A representative article: https://sandwalk.blogspot.com/2013/07/five-things-you-should...
[2] Rabbit hole warning, all of his Junk DNA posts: https://sandwalk.blogspot.com/2008/02/theme-genomes-junk-dna...
As for appendix, it seems to be home for bacteria that can cause dementia but are otherwise useful in the gut. I don't know if that's actually its purpose, but if so, it seems pretty important.
The core of this ongoing debate is mainly about some regions, like Alu, which appear to truly have no function, and have little to no functional effect. I think scientists could still make a good faith experimental effort at attempting to salvage this idea, see Eddy's proposal about a "neutral genome" here: https://www.cell.com/current-biology/comments/S0960-9822(13)...
The fairest way to describe it is that scientists continually find that more and more DNA that was neglected as having zero functional (no observable, measurable, directed activity that is under evolutionary selection pressure) effect, does indeed affect the fitness of organisms in ways that are not accomodated by existing theories of gene expression or regulation. It seems unlikely, however, that we will ever truly be able to point to every single base pair in teh genome and say "it's under functional pressure", and if that's the case, it's easy to make the argument that some of it is "junk".
However, complex information processing systems like life don't really fall into simple classification, "junk" is really a subjective term, we should focus instead of measurable scientific phenomena like fitness.
Today, we still use leeches but only for those cases where they can provably affect the cause.
Or maybe to put it in another way, in terms of usefulness, is that the 'junk DNA' holds the same significance as the programming header files do. Maybe we should be calling those data sequences of DNA as 'junk.h'.
I venture to say that maybe only 0.1% of the stuff we call 'Junk DNA' (or even none of it) is irrelevant.
It’s like you have a bookshelf filled with books. Some books you haven’t read, some were gifts, some were acquired, some you didn’t finish and some book you will read over and over again. All of them were kept for some reason.
I don’t believe nature would create something that’s completely useless. I just know that often I fail to see what the use might be.