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The Complex Truth About ‘Junk DNA’
- rflrob 5y agoParagraph 4: “Slowly, slowly, slowly, the terminology of ‘junk DNA’ [has] started to die,” Rest of the article: continues to use the term "Junk DNA".
- hateful 5y agoI think more than any other group, programmers can understand the gut reaction of calling code that they don't understand "junk".
- f6v 5y agoEveryone 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.
- dekhn 5y agoit'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 https://en.wikipedia.org/wiki/Paris_japonica). The cost of DNA replication isn't that strong a functional selection afaict.
- taneq 5y agoSounds like "non-functional DNA" might in fact have a function, hm?
- dekhn 5y agoProbably 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.
- thaumasiotes 5y agoNon-functional DNA is to all DNA as source code that doesn't call I/O is to all source code.
- IncRnd 5y agoYou're conflating the size of a genome with the amount of DNA that is non-functional.
- dekhn 5y agoI'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.
- IncRnd 5y agoDNA that doesn't encode proteins is not necessarily non-functional.
- dekhn 5y agoYes, 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. See http://cryptogenomicon.org/encode-says-what.html http://cryptogenomicon.org/encode-says-what.html and https://www.cell.com/current-biology/comments/S0960-9822(13)00289-3 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 https://www.pnas.org/content/110/14/5294 and https://www.mun.ca/biology/scarr/MGA2_02-10.html 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=pdf&doi=10.1.1.209.118 http://citeseerx.ist.psu.edu/viewdoc/download?rep=rep1&type=...)
- otherme123 5y agoIf 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.
- taneq 5y agoIntroduction: Introduces term. 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.
- burnished 5y agoWhat 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.
- inglor_cz 5y agoFamously, people with multiple copies of GGGGCC in a particular section of their non-coding DNA are prone to horrible neurodegenerative diseases including ALS (shudder). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202986/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202986/
- nextos 5y agoMost 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. [1] https://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1285-0 https://genomebiology.biomedcentral.com/articles/10.1186/s13... [2] https://www.nature.com/articles/nature13138 https://www.nature.com/articles/nature13138
- f6v 5y agoThe 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.
- nextos 5y agoThere'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.
- otherme123 5y agoFor 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.
- jes 5y agoSince 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.
- throw3849 5y agoNot really. Smaller DNA means smaller surface, and less total accidents.
- nitrogen 5y agoHypothetically, 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.
- throw3849 5y agoIt is not square area, but cubic area (mass).
- gazookgaboot 5y agoSee "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. https://academic.oup.com/gbe/article/5/3/578/583411 https://academic.oup.com/gbe/article/5/3/578/583411
- thriftwy 5y agoNon-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.
- throw3849 5y agoAt 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.
- callesgg 5y agoTo 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.
- favoritecolor 5y agoI 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. [1] A representative article: https://sandwalk.blogspot.com/2013/07/five-things-you-should-know-if-you-want.html 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.html https://sandwalk.blogspot.com/2008/02/theme-genomes-junk-dna...
- bigodbiel 5y agoIs junk DNA still alive? I thought we have all jumped ship to non-coding DNA a long time ago. It was fun while it lasted, that’s for sure!
- shakil 5y agoAny 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.
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- ksaj 5y agoThat 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.
- dekhn 5y agoThe 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.
- dekhn 5y ago.... 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)00289-3 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.
- peter303 5y agoNon-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.
- 8bitsrule 5y agoThe 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.)
- simonblack 5y agoComputer 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.
- miika 5y ago“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.