Theoretical biologist here. This is an incredibly important book. I just bought it a few minutes ago and so I’m only partway through the beginning, but it’s summarizing everything people from my school of thought (complex adaptive systems theory, multilevel selection models, and so on) have been arguing for two or three decades. It’s a very fast read so far (probably less so if you’re less familiar with the points the author is making), but I really hope that this book has an impact that’s reflective of the timeliness and cohesiveness (as I am reading into what the author is preparing to argue) deserves.
this post was submitted on 07 Feb 2024
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Maybe finish the book before you decide?
If you’re familiar with the subject, you can tell exactly where the author is going to go with it. I’ve been working on and teaching this material for about 20 years, and I’ve applied it against quite a diverse number of areas.
I’m not learning anything new from the book, but simply reading a well-assembled argument as to why it should become a dominant paradigm.
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Yeh! Good to see the rusty machine (and self-deprecating) model fading away and being replaced by real appreciation of the true marvels that have emerged over millions of years. (Science's mechanical models were all so ... 18th century!)
(Not so familiar with biology but did enjoy hearing about the tack Lee Cronin's taken.)
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What a dishonest bs. It's not the scientists who communicate these dumbed down "theories", it's journalists and trivial science books and shows.
Makes me loose all respect for the author.
At the university where I studied professors were constantly talking about what we don't know. Formulated every theory extremely carefully, there was no "it is like that". What kind of scientists is he talking about?
Yeah, I graduated with my BS in zoology over 20yrs ago and my professors wouldn’t have talked about genetics as a blueprint even back then. My focus was evolutionary biology and the one sentence in the article on the topic made me cringe. I would guess that people who focused in molecular bio probably cringed through the rest of it.
Another metaphor that Ball criticizes is that of a protein with a fixed shape binding to its target being similar to how a key fits into a lock. Many proteins, he points out, have disordered domains — sections whose shape is not fixed, but changes constantly.
I dunno, kinda sounds to me like a good educational metaphor. Yea, not 100% accurate but good enough for high school biology. You need to make some simplifications for the sake of education. Not everyone can care about the complex intricacies of genes and proteins.
Good enough for high school biology. But not when you're doing influential cancer research. The following is from Subanima's article on the same subject:
One of the most influential papers in cancer biology published in 2000 was the "Hallmarks of cancer" by Douglas Hanahan and Robert Weinberg. It outlined six of the main capabilities of cancer and laid out a rough program for studying the disease ointo the 21st century. To date, it has over 39,000 citations which, in academia, is officially known as a shitton.
It was so successful that they released a sequel in 2011 which has over 62,000 citations - also known as a metric shitton.
But at the heart of both papers is the machine metaphor and the idea that if we just map out all the functions of proteins in one ginormous map, we'll just have to run some maths and we'll know everything we need to know to cure cancer. In 2000 they wrote:
Two decades from now, having fully charted the wiring diagrams of every cellular signalling pathway, it will be possible to lay out the complete ‘integrated circuit of the cell.’
He also notes the same thing you noted, that it's a good metaphor for high schoolers.
I still feel like he's nitpicking tbh, wiring diagrams can have devices with variable or probabilistic states and though the maths is very complex it's theoretically possible to similate and map.
This maybe true, but these states aren't being represented in the biological diagrams.
Why can't we have both?
Edit: switched what to why.
I think we will. It's still a useful analogy for initial understanding. However, I think we should be clear that it's not quite perfect. Just like we have to be careful about bringing a Newtonian understanding into quantum physics where someone might believe a photon has mass because it has momentum.
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.
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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.
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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.
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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.
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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
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?
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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.
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