It’s time to admit that genes are not the blueprint for life
It’s time to admit that genes are not the blueprint for life
The view of biology often presented to the public is oversimplified and out of date. Scientists must set the record straight, argues a new book.
Review of 2023 book: How Life Works: A User’s Guide to the New Biology Philip Ball. ISBN9781529095999
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Craig Venter, the infamous head of the Human Genome Project and who created the first "synthetic" cell, has been saying this stuff for years. It's remarkable how ahead of the times he is, perhaps because he's not beholden to an academic institution.
He claims that a "tree of life" is fallacious, that there is no junk DNA, and that the bare minimum genes necessary for a living cell still can't be determined even after decades of research.
I hope that the authors of the new Extended Evolutionary Synthesis will admit the deficiency of outdated assumptions and reject dogmatic approaches to the theory, as implied by the author of the book reviewed in this article.
How could there be no junk DNA? There are plenty of inserted regions of repeating codons, between regions that are read (outside of replication). DNA replicators are very simple machines, they copy until they're told to stop, I agree that any junk DNA in the human genome has been there for a very long time, but it's not difficult to find single cell organisms that have introduced previously non-self DNA in their genome. If that DNA isn't used besides replication then it's junk is it not?
Also telomeres are pretty synonymous with junk DNA, until they aren't, or is every shortening of the telomere removing information vital to a cells function?
So I think I can make the claim that I am an expert in this, at least compared to 95%+ of biological researchers. My research foci include epigenetic and emergent interactions like the ones discussed in the article, and although I am not going to back this up by identifying myself, please believe me when I say I've written some papers on the topic.
The concept of junk DNA is perhaps the problem here. Obviously there are large swaths of our genome that do not encode anything or have instructions for proteins. However, dismissing all non-coding DNA as "junk" is a critical error.
Your telomeres are a great example. They don't contain vital information so much as they serve a specific function-- providing a buffer region to be consumed during replication in place of DNA that does contain vital information. Your cells would work less well without telomeres, so calling them junk is inaccurate.
Other examples of important non-coding regions are enhancer and promoter regions. Papers describing the philosophical developments of stochasticity in cellular function note how enhancers are vital for increasing the likelihood of transcription by making it more likely that specific proteins floating in the cellular matrix interact with each other. Promoter regions are something most biologists understand already, so I won't describe them here (apologies for anyone who needs to go read about them elsewhere!). Some regions also inform the 3D structure of the genome, creating topological associated domains (TADs) that bring regions of interest closer together.
Even the sequences with less obvious non-coding functions often have some emergent effect on cellular function. Transcription occurs in nonsense regions despite no mRNA being created; instead, tiny, transient non-coding RNAs (ncRNAs) are produced. Because RNA can have functional and catalytic properties like proteins, these small RNAs "do jobs" while they exist. The kinds of things they do before being degraded are less defined than the mechanistic models of proteins, but as we understand more stochastic models, we are beginning to understand how they work.
One last type of DNA that we used to consider junk: binding sites for transcription factors, nucleosome remodelers, and other DNA binding proteins. Proteins are getting stuck to DNA all the time, and then doing things while they're stuck there. Sometimes even just being a place where a nucleosome with a epigenetic flag can camp out and direct other cellular processes is enough to invalidate calling that region "junk".
Anyway I'm done giving my spiel but the take home message here is that all DNA causes stochastic effects and almost all of it (likely all and we haven't figured it out yet) serves some function in-context. Calling all DNA that doesn't encode for a protein "junk" is outdated-- if anything, the protein encoding regions are the boring parts.
Thank you for taking the time to respond, I respect your knowledge and agree with you for the most part. From an evolutionary perspective there's very little pressure to cull genetic material that does not have a purpose, genome replication is already taking place and takes very little overall energy/time.
There may not be as much useless DNA in the system as previously thought, but not every codon pair has a use. There are undoubtedly identical transcription codes being suppressed in one section of DNA that are active in other regions, and it may have been useful to have that extra region available if pressures ever applied that caused that region to be reactivated, but if mutation occurred and caused that region to no longer have the original blueprint it was coding for, it could theoretically create actual evolutionary pressure to eliminate/suppress that section of the genome, it could be suppressed/inactive harmful DNA, not junk but also not beneficial.
My biggest hang-up on the whole "every codon has a purpose" argument is that it blatantly ignores the evidence occurring so much more frequently at "lower" life forms. Eukaryotic single cell organisms swap DNA rather readily, it's a much higher risk/reward mechanism of evolution, a lot of that DNA, if it turns out to be beneficial, will be ancillary to the actual genes with benefit. Plants have genomes that vary in length from generation up generation, often times much larger than required, maybe it's because they chill in the sun all day and are more susceptible to genetic mutation, but just because there's extra targets for codon swapping, doesn't mean that DNA is set there with purpose. It just exists. It may have been beneficial at one point, but it's only there because it isn't detrimental enough to have selection pressure repercussions. If pressures were high enough they every codon mattered, (or if it were designed intelligently so that every codon mattered) a lot of genomes (I'm not to nervous to claim I believe all genomes) would be shorter due to junk culling, it's just such a small factor in the schema that it isn't ever selected against.
I would encourage you to read the linked Science paper and Dan Nichol's paper, Is the Cell Really a Machine?
You feel that if a codon isn't meant for something, if it doesn't have a purpose-- then it is junk. This is a mindset that is reflective of the machine model of the cell. We used to expect that each protein was bespoke for a function, each transcript necessary.
The whole paradigm shift at hand is this model falls flat, even for coding regions. I think you're actually very spot in here with the prokaryotic DNA or the plant genomes (love me some violets for their weird genomes). Some parts of a genome will rapidly change and appear to serve no real purpose, but the next bite is the important one: even if it seems like there isn't a purpose, like a top-down prescription for functionality, those regions are still doing something while they are present.
For example, some long non-coding regions affect the likelihood that a person will develop Parkinson's disease, or in the case of plants with various polyploidies, the relative expression of their genes won't necessarily change, but the absolute expression may.
Basically, you aren't wrong that these regions dont have a purpose, because no genes have a purpose. The cell isn't a machine.
Three cheers for Dan Nichol's paper.
Here's a direct link to the PDF found on Philpapers.org.The cell isn't a machine.
What do you mean by this? I feel like you think the meaning is obvious after everything you've said, but it's not.
Even if we accept that everything you said is true, all it means is that the cell is a very, very complex machine. More complex than current models account for. It's just chemistry, after all. The chemicals behave in predictable fashion or else life wouldn't be possible at all. Molecules moving around, transforming, causing other molecules to transform, etc, etc, to turn food into shit and babies. You can always use the word "machine" to describe that, no matter how complex it is. Just like the word "algorithm" can be used to describe the function of code no matter how complex it is, whether it's a simple path finding algorithm, or the newest machine learning one.
But I probably shouldn't use the word "function" because that implies purpose, and, as you say, no part of the chemistry of life has purpose. I hope you can detect my snark. That's a pretty lame argument that's philosophical at best. The purpose of the machinations of the cell is to maintain life and reproduce. No mater how many times you say it, your words won't change the fact that that is the purpose of the chemistry of life.
You've twisted around the word "purpose" in your head until it has no useful meaning. Nonsense. A molecule can many overlapping, hard to discern purposes. That does not mean it doesn't have a purpose.
When I say "the cell isn't a machine", it is in specific reference to the machine model of the cell, which is a previously established conceptual framework in the field of molecular biology. If you want to understand why that model is falling out of favor today, you're invited to read the article linked by OP and/or the articles I have linked in other comments.
The gist is that the cell is more complicated, flexible, and emergent than any machine has ever been and will be for the foreseeable future, and the idea that we can simply map the functions of each molecule in the cell to get a perfect "circuit diagram" of how everything plays together is defunct.
I don't have time to mess with this thread any more. You can either accept what myself (an expert in this field), the author of this publication (which happens to be one of the most prestigious journals in the world), and others who do this research daily are saying about this, or you can not. Frankly, if you are an expert also, the field, the research, and the truth barely cares about our opinion-- it certainly doesn't care about non-expert opinions on the internet.
So, shall we call it "inactive regions" then?
'Noncoding region' seems to be the preferred term.
No, because they are anything other than inactive
I'm not an expert on the subject. I can only repeat what Venter said: "the only junk DNA is in my colleagues brains". He claims that all DNA has function and that it should not be referred to as junk just because we don't know the function yet.
He needs to look at some plant DNA, there are places with 50 times now DNA codons per cell than Humans have, with many many many times fewer genes.
"If it's there it must be there for a reason" sounds an awful lot like intelligent design to me, and his putting down his colleges for holding alternative (seemingly more informed than his own) theories doesn't help my view of him. More codons don't mean more reason, evolution is not what is most efficient, it's just what works best at any time. It's also full of cross contamination at the simple life form level, and what's good for one single cellular life form might benefit another life form, but the entirety of that first life form isn't necessary for the second, so evolution would suggest that the absorbing life form will slowly whittle down what isn't necessary.
Or has mitochondria always been perfectly fit for it's function in our cells? (Hint it hasn't)
I don't think that Venter is suggesting intelligent design. He's claiming, as a result of his research, that it's not effective to assume simple explanations for genomics and especially for cellular biology.
Every technological improvement in the methods of research has revealed more complexity in organisms and so it behooves us to suspend dogmatic approaches to the genome. That's the subject of the book discussed in the article.
Craig Venter is very controversial and his statements are provocative. I'm not qualified to critique the science in this field. But I'd recommend you to take a look at the work his team is doing with synthetic chromosomes and engineered cells.
If there is a random mutation that is neither advantageous nor disadvantageous, wouldn't that be junk DNA?
Are we going to say we need to see how every descendant of the creature fares before we can decide whether it was junk DNA or not?
'Junk DNA' is any DNA whose purpose was unknown when the article / book was written. But to return to your question, not necessarily.
First, we are usually concerned with the (dis)advantages of mutations when they occur in coding regions, which are definitely not junk DNA.
Second, just because a sequence does not encode any useful information does not mean it is useless. For example, it could be holding a coding region away from another, so both can be transcribed at the same time. Or it could be structurally important in the way the chromosome is folded.
I don't know too much about the subject, but maybe this almost 30 year old article can help. There's more specific examples in the article, but this quote captures the direction:
"I don't believe in junk DNA," said Dr. Walter Gilbert of Harvard University, a pre-eminent theoretician of the human genome. "I've long believed that the attitude that all information is contained in the coding regions is very shortsighted, reflecting a protein chemist's bias of looking at DNA." Coding regions may make the proteins that are dear to a chemist's heart; but true biologists, he added, know that much of the exquisite control over these proteins is held offstage, nested within the noncoding junk.
A pretty deus ex machina approach.
How would the size of this plants genetic code be justified I wonder?
https://en.m.wikipedia.org/wiki/Paris_japonica
There are plenty of plants that execute the exact same functions with code thousands of times smaller.
To say every codon has a purpose is to be ignorant of how evolution works. There are start triplicate pairs and stop triplicate pairs, the regions between stop and start don't need to have function, even structurally, otherwise why would chromosomes come in different lengths? There was no creator of the genome, there was no efficiency driven outcome, there's only descent with modification, things just happen to with the way they work, and that's beautiful in it's own way.
Again, and I can't emphasize this enough, this is not my area of study and seems like you have better handling of the subject. But when I read his quote, this part sticks out to me:
much of the exquisite control over these proteins is held offstage, nested within the noncoding junk.
Additionally, the article calls into question the role of code and protein production as the only role for DNA.
Still other noncoding stretches may be buffers against precipitous change, serving rather as flak jackets to absorb the impact of viruses and other genetic interlopers that infiltrate an animal's chromosomes. Without all the extra padding to absorb the blows, viruses or the bizarre genetic sequences that hop and skip from one part of the chromosome to another -- mysterious genetic elements called transposons or jumping genes -- might land smack in the middle of a crucial gene, disrupting its performance.
So there maybe stretches of DNA that don't participate in protein construction, but still has a role. So I question I idea of centering one type function over another.
@TempermentalAnomaly @morphballganon
Junk dna was junk science from the start for ignoring that evolution often eliminates or reduces useless things, like eyes in cave fish, so there’s little likelihood that there’s useless parts of the genome.But it doesn't do that instantly and it does it for good reason, eyes and the sections of the brain using them require energy and are vulnerable to infection so in situations where they don't provide an advantage they increase the likelihood of death before breeding thus giving any offspring born with less energy devoted to eyes has a small advantage which over s very long time results in them being selected away.
So unless the creatures reach a perfect form for their environment then they'll always be in the process of changing and have some of the old junk in there. Also if the formerly useful part doesn't make any real difference to survivability there's no force driving it to be selected away from, it might eventually be removed by lots of pure chance events but that's going to take a huge amount of generations meaning the middle time where there's junk not yet removed us going to be very long
Junk DNA is repeating codons, or codons that occur in areas that are outside of the "start/stop" codon triplicate pairs. A DNA transcribing protein will read the genetic code from a start signal, until it gets to a stop signal. Then it clips itself off the chain and re-binds the chain together for the next transcriber to use. Sometimes there are extra codons between a stop signal and the next start signal, sometimes there are hundreds of thousands of extra codons. They aren't there for structural reasons, all DNA is the same 4 codons linked together over and over, all the different chromosomes are different sizes. All of this DNA is reported when the cells divide, that's the only time those regions between the stops and starts actually come into play. This is very easily proven, we know the structure of the reading proteins down to the molecule (indeed there are starts and stops and triplicate base pairs that design these transcribing proteins). The "important" junk DNA that has significance while not being in a "start->stop" zone are the codons that occur before the first start codon on either side of a DNA strand, when DNA is replicated the protein that starts replicating it has to start at 1 end of 1 side of the DNA in order to be able to read it, except it needs to find the end first, and to make sure it's all the end it "clips" the first 6 (? Maybe more maybe less, it's been decades since I've studied this) codons from the strand of DNA, this is lost for all future replications of the cell, your DNA actually gets shorter every time your cells reproduce (except your miosis division cells, they have a special replication process that keeps the full length of every chromosome).
Sorry for the wall of text, but there's plenty of examples of blatantly junk DNA, and there are known methods of how it occurs. Anyone who says every codon pair has a purpose has a screw loose and is ignorant to the mechanics of evolution.
Junk DNA is repeating codons, or codons that occur in areas that are outside of the "start/stop" codon triplicate pairs.
Those sequences do things and have effects. In fact, the coding regions are often less functional than the non-coding ones.
They aren't there for structural reasons, all DNA is the same 4 codons linked together over and over, all the different chromosomes are different sizes.
Sometimes they ARE there for structural reasons? Read: enhancers, or CTCF binding sites? Among many other myriad examples of functional noncoding regions? Also, nucleotides =/= codons. There are 64 codons.
All of this DNA is reported when the cells divide, that's the only time those regions between the stops and starts actually come into play. This is very easily proven, we know the structure of the reading proteins down to the molecule (indeed there are starts and stops and triplicate base pairs that design these transcribing proteins).
That's bull. You're out of your depth. A contemporary college molecular biology course would show your examples to the contrary.
The "important" junk DNA that has significance while not being in a "start->stop" zone are the codons that occur before the first start codon on either side of a DNA strand, when DNA is replicated the protein that starts replicating it has to start at 1 end of 1 side of the DNA in order to be able to read it
I feel like a broken record but Enhancers! lncRNAs! siRNAs! Binding sites! Other gene regulatory regions! Epigenetic nucleosome modifications! Chromatin remodeler sites!
except it needs to find the end first, and to make sure it's all the end it "clips" the first 6 (? Maybe more maybe less, it's been decades since I've studied this)
Oh, there's your problem. A lot has changed. You refuse to see the sea change happening around you because it means you're out of date.
Sorry for the wall of text, but there's plenty of examples of blatantly junk DNA, and there are known methods of how it occurs. Anyone who says every codon pair has a purpose has a screw loose and is ignorant to the mechanics of evolution.
I was happy to reply to you and engage pleasantly originally but you are only engaging with people that know less about biology than you do. You are not an expert if you last studied biology decades ago and can't remember the details. You certainly aren't enough of an authority on the subject to question a contemporary article published in Science or the work of other researchers currently in the field.
I really, really encourage you to read these papers thoroughly. You are the target audience-- people who learned the machine model of the cell and who are gripping it so tightly that they are blind to the nuance that we've uncovered. I also encourage you to not write insults about people who disagree with you, especially people with more domain knowledge than you have.
Every sperm isn't sacred and every piece of DNA isn't with purpose, otherwise explain ferns and plants having hundreds of times more DNA than higher functioning life forms.
Where did I write an insult??
Not an expert but it's easy to see that information is not function. Like in computers, a sequence of bytes in memory can encode both operations and data. A single byte can be both. The two also mix up in dna, and adding a new random chunk of data to a mechanism like that will alter the expression, the fInal output. If an action must be repeated on all the elements of a list, and you add three random elements to the list, the result of the program changes. So no, it's perfectly believable that there is no junk dna.
I'm sorry, but this is not computing, if it were you could think of DNA as an old spinning hard drive, sometimes you need to put pieces of data that will end up creating the program you're going to run on different sides of the disc, fragmented memory if you will, you don't need to read everything in a row to make the file, you need 8mb chunks there and there, there are start and stop codons that tell the RNA transcription proteins when to read and when to stop reading, and there are sometimes entire other genes between two sections of DNA that will eventually be "working in the same program". There's no need to read an entire strand of DNA, it's not even done that way when the cells divide, it's actually not possible, except in gamete production, to read the entire strand, because there's a bit of extra (junk, telomeres) that cannot be read and reproduced, your DNA gets shorter every time your cells divide.
Structural similarities are most important (though still negligibly so) in recombination during meiosis, but even then the recombination is happening between strands of DNA of inherently equal lengths.
I believe you're confusing DNA with protein formation when you're saying the structure is important, there are many areas of DNA that have unnecessary lengths of extra codons. If you don't believe this please look at plant genomes, there are some that are thousands of times larger in terms of base pairs, that have hundred times fewer genres.
See here for an overview of the current thinking on junk DNA: https://www.news-medical.net/life-sciences/Functions-of-Junk-DNA.aspx
Basically there are a variety of indicators that suggest A - Many "junk" regions are in some way evolutionarily important because many sections of "junk" are preserved across time, which, given the way DNA works, would almost certainly not be the case if they had no function, B - there is evidence non-coding regions actually do influence when and how other genes are expressed.
In essence, you could look at it as possibly metadata or maybe something very loosely along the lines of a Makefile for genetic code.
I think the assertion that it's not "junk" is more alluding to the fact that although it does not directly encode proteins, asserting that non-coding proteins are "junk" requires us to ignore that there is clear evidence that non-coding regions likely do serve other purposes, or rather, requires us to proactively assert they serve no purpose simply because they don't serve the very first purpose we hypothesized they should serve.
If a gene becomes disabled (a start triplicate pair gets changed to a nonsense triplicate), and it turns out that gene was no longer useful so there's no impact on survivability/reproduction, what happens to the rest of the pairs before the next start triplicate? That stop triplicate and everything before it is now useless. Except evolution doesn't understand useless, there's just as much chance of flipping that gene back on as there is of shortening all of that non readable DNA by just 1 codon length, DNA replicators are very good at not dropping codons. But not you have a gene that isn't being read (outside of replication) or transcribed, and it really isn't costing the individual any significant amount of extra resources to continue to produce that set of code in that strand, so it just hangs out.
There are dozens of other mechanisms to control the rate of protein synthesis, why would junk DNA be the controlling mechanism for it when there are epigenetics, gates, chemical limits, so many different ways rare limit down the path.
"It's there so it must have function" is spitting in the face of the theory of evolution. "It's still in the genetic code so it must've been selected for" is barely less offensive. Evolution does not select for efficiency, it's descent with modification, there is no pressure that says the genetic information must be as efficiently contained as possible. Example: https://en.m.wikipedia.org/wiki/Paris_japonica
Also I'm not at all arguing that proteins are junk (also not saying they're peak efficiency, but "junk" in a 'read' section of DNA is clearly not 'junk'), I'm arguing there are sections of DNA, especially repeating sections outside of start stop sections, that are without purpose.
This is a funny comment though, because "junk" DNA is involved with epigenetic regulation and cellular behavior.
"It's there so it must have function", "it's still in the genetic code so it must have been selected for" is the least nuanced take,
"It's there just randomly and therefore is junk", and "evolution does not select for efficiency" is an improvement,
But "it's there and it's doing something despite not having a bespoke, prescribed function" and "evolution is a cascade of emergent effects and random chance, none of our genome is non-functional even though it is random" is the most up to date take
You seem like a biologist, why not go read some of these papers? Like the one I linked by Dan Nichols? Most people don't have the background necessary to understand the language (no shade) but you seem to!
You can second-guess the current state of the literature on junk dna all you want but unless you have a research budget it's a bit meaningless.
Also, I never said, and no scientist said, it was THE SINGLE AND ONLY mechanism influencing gene expression. Nobody also ever said the fact the "junk" is preserved was the CONCLUSIVE AND DEFINITIVE PROOF that it does something. Just that it's a good indicator.
You're not really responding to what the current hypotheses are.
Thank you for your answer, I will look up those things. Kind of an aside but regarding the dna getting shorter my undertanding was that it only happens when you get older and you don't produce enough telomerase anymore that usually compensates the damage by extending the telomeres so the actual dna is not reduced during duplication.
Which theory exactly are we rejecting dogmatic approaches to?
There are several. One is the gene-centric theory of biology, which carries less weight in biology itself than it does in how biological sciences are communicated to laypersons - eg the Selfish Gene, which I could rip on for pages - and others include ideas that are considered contentious within biology, such as multilevel selection theory that extends beyond kin selection. I can’t begin to tell you about the number of arguments I’ve gotten into on that subject alone. I will frequently bring up that there is confusion as to what a “gene” actually is, and how it’s really determined by the context in which we’re using the word. There’s really just so much that needs to be re-evaluated.
" the Selfish Gene, which I could rip on for pages "
Please put me on the list to read that!
Ditto!
i believe the article suggests that the current way of communicating biology - that genes are the code that runs the machinery of life - is dogmatically adhered to by science communicators
it also suggests that when we communicate our new understandings that we are careful not to fall into another dogmatic theory, because it’s complex and we just don’t know
this is language used in the article, i don’t have enough information or understanding to know whether it’s true or not
It's published in Nature or Science. Which means it's better than the thruth (which we don't have access to!), it's high quality science.
Really good science news communicators (including many teachers because how are admins to judge?) are too rare ... on YTube there's ... a half-dozen, maybe, at best?
Fraser Cain for astronomy
I linked to this in another comment, but figured you'd dig it.
https://www.subanima.org/veritasium/Sure large proteins have multiple forms and functions, but we do know the exact makeup shape and function of a lot of the smaller ones, like the ones that are small enough to get between either strand of an opened helix to read, transcribe, and send for translation the code for the larger proteins (anything inside the nucleus). Saying all proteins are inherently not understandable because there are large proteins that we don't have full understanding of, is just as incorrect as saying we know every function of every synthesized protein.
Also I can't stand veritasium, he gives over simplified, easy to latch onto, "explanations" of questions and misses out on a lot of minutia that would actually lead to a better understanding of why these questions exist. But people on the Internet love that stuff because they get an answer and are enabled to say "well actually" next time the topic comes up even though they've barely gotten any of the details of the problem itself. Pop science at it's worst. Him and numberphile both
veritasium has also had some controversy around misleading half truths for click bait right?
i think it’s worth knowing the creator so you can appreciate it for what it is: not a source of truth, but a source of entertainment that if you find something fascinating you can look for other sources on… he does do entertaining videos with a science twist quite well, and uncovers some interesting topics… just not the be all and end all
There are way more than half a dozen, they're just too dry to get the algorithm's/communities attention. Most Internet viewers want an answer in x minutes or less, they don't care to understand what the details of the questions are. If an answer is able to be given in a few minutes, why would the question exist for centuries?