The Complex Truth About ‘Junk DNA’
quantamagazine.org
quantamagazine.org
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...
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.
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.
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...
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.
Rest 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.
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.
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.
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.