this post was submitted on 07 Feb 2024
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Review of 2023 book: How Life Works: A User’s Guide to the New Biology Philip Ball. ISBN9781529095999

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[–] [email protected] 36 points 9 months ago (2 children)

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.

[–] [email protected] 7 points 9 months ago (1 children)

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.

[–] [email protected] 5 points 9 months ago (2 children)

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.

[–] [email protected] 1 points 9 months ago

Three cheers for Dan Nichol's paper.
Here's a direct link to the PDF found on Philpapers.org.

[–] [email protected] 0 points 9 months ago* (last edited 9 months ago) (1 children)

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.

[–] [email protected] 1 points 9 months ago

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.

[–] [email protected] 1 points 9 months ago (2 children)

So, shall we call it "inactive regions" then?

[–] [email protected] 5 points 9 months ago

'Noncoding region' seems to be the preferred term.

[–] [email protected] 3 points 9 months ago

No, because they are anything other than inactive