A DNA ‘parasite’ may have fragmented our genes

https://www.quantamagazine.org/how-a-dna-parasite-may-have-fragmented-our-genes-20230330/

by theafh • 3 years ago

156 79 3 years ago

dboreham• 3 years ago

Sometimes little frustrating that people writing articles in this field seem to have no exposure to computer science.

This is the gene equivalent of a filesystem: the DNA fragments are like disk blocks. The interposing sections are file metadata. The shearing mechanism is the filesystem reconstructing a stream from the lower layer blocks. There's probably some redundancy and error correction in there too.

It needs a filesystem for the same reason they were invented for computers: to provide an impedance match between the upper layer semantics (a stream of pairs describing a protein) and the lower layer storage (blocks). Using block structured storage is more flexible in terms of being able to insert in the middle of a file, etc etc.

monocasa• 3 years ago

I don't think that's a great comparison. Exons already have sequences that mark 'block' boundaries; amino acids are encoded in triplets of base pairs, but sort of like you see in 8b/10b encoding, there are sequences that are valid but only used for control purposes and don't correspond to amino acids.

rco87862• 3 years ago

That's a weird thing to get frustrated about...that someone in a completely unrelated field didn't have the experience or courtesy to explain something using analogous terms to the thing you happen to be an expert on.

aeonik• 3 years ago

I don't think they are unrelated fields. Computer science is the study of computation. DNA, to me, is clearly a quaternary computation system.

I think there is a lot for both fields to learn by studying knowledge from each. Bioinformatics seems to be on that track.

vkou• 3 years ago

Doubly so, when the two domains don't actually map cleanly to eachother. DNA is not a computer program, or a file, or storage. There's no real distinction between data, metadata, and 'code' in it, either in structure, or in practice.

afavour• 3 years ago

I don’t want to sound dense here but why is it frustrating that people who write about genetics aren’t familiar with computer science?

agumonkey• 3 years ago

I can have similar thoughts at times. People in one field have their own lens to see the world and might miss some structures / patterns that exist in other domains. I felt it was a bit pompous to read a few medical books about the cardiovascular system, a lot of ceremony to describe an organic pump. You'd have to read mathematically inclined papers to start reading about equations and principles rather than latin nomenclature. Which I think is what the grandparent was wishing for.

ps: I absolutely do not put computing above other fields though. I just wish for some pragmatic polymathism sometimes.

elchief• 3 years ago

I suppose because they spent 6-8 years of their early adult lives focusing exclusively on biology and not computer science

sorokod2• 3 years ago

It needs a filesystem for the same reason they were invented for computer

Why would that be true? It is a cool analogy but implying that it is the reason requires much more.

renewiltord• 3 years ago

Without taking a stance on whether it's right, I believe that is explained right after your quote cut-off.

kleer001• 3 years ago

https://en.wikipedia.org/wiki/Curse_of_knowledge

otherme1233• 3 years ago

There are organisms with almost no introns, no redundancy, no CRC, no "metadata" and even overlapping genes to save space, like Giardia genome ( https://www.science.org/doi/10.1126/science.1143837 ). Lots of virus have all their genes encoded without introns, and almost all the genome is encoding something.

I've never seen DNA as close to a filesystem, and our current best bet on introns functions are they are used to create alternative splicing products from the same DNA chunk. I cannot identify this function in a filesystem, where you can obtain two or three different valid files from the same data just by skipping some blocks.

pazimzadeh3• 3 years ago

What is CRC?

Metadata is everywhere... histone modifications, glycosylation, etc..

GauntletWizard2• 3 years ago

I can - It's called COW Snapshotting. Modern filesystems like ZFS and BTRFS don't ever overwrite parts of the file that change. They abstract it away by keeping an ordered list of blocks. Snapshots are simply copies of the old list.

The analogy doesn't go very far, however.

inciampati• 3 years ago

I don't like appeals to authority, but as a computational biologist, I am both a computer scientist and a biological scientist. So understand that I'm responding to you as exactly the kind of person you think should be drawing the kinds of links that you're suggesting.

I'm sorry, but this is just not a reasonable analogy. DNA sequences are not like computer files. The reason that they're distinct modules in these sequences is due to the need for evolution to be feasible. And also for the basic reason that the sequences are linear and so modules tend to appear in these linear sequences. But there also tremendous nonlinearities as well. Things at very long distances can be importantly related to each other.

The introns are not metadata. There are regions that can be removed selectively and in combinations to cause diversity in the produced proteins. That diversity is advantageous because it allows a single DNA sequence to present many different proteins that are typically related, but can be very different structurally. This splicing capability has evolved apparently from entities that can be seen as endogenous viruses or DNA parasites that have the ability to insert and splice themselves out of DNA and RNA sequences. In many confusing words, that's what the article or pointing at is talking about.

The introns do provide a kind of redundancy, but only in the sense that there are areas that can be modified with minimal effect on cellular function, at least relative to modification of the exons, which directly correspond in a one to one way with proteins.

There is error correction. It's called homologous chromosomes. Everyone talks about there being one genome, but in most complex forms of life, you have more than one copy per cell, usually two, and often more. These multiple copies, in addition to allowing for recombination and sexual reproduction, provide templates on which errors which arise during life can be corrected. However, there are no error correcting codes.

If you'd like to learn more about the actual details of these systems, I strongly suggest an undergraduate molecular biology textbook. The best one in existence is called the Molecular Biology of the Cell.

There are indeed many similarities between computing systems and biological systems, but the analogies you are making don't appear to be clear. Read a book like this, deeply and slowly, and it might change your life. At very least, it'll mean that the world you live in is much less mysterious and much more exciting.

pazimzadeh3• 3 years ago

Aren't introns like pieces of code that have been commented out?

But they also change the 3D conformation of the DNA itself, which changes access by transcription factors, etc.

notfed• 3 years ago

"Molecular Biology of the Cell"

Shout out to this book. Not only has the most amazing imagery, but you can learn a lot just by skimming the book, because of how well organized it is.

gus_massa3• 3 years ago

You look interested in the subject, but I recommend to read a few biology books about it. There are many weird low level features of DNA that are not so cover in popular discussions [1] [2]. But I don't remember any that is similar to a filesystem as you propose. Take a look, you will be gladly surprised.

[1] One of my favorites is that the bases of ADN are translated in groups of 3 to amino acids, so the code reads like

  AAABBBCCCDDDEEEFFF

It's very unusual, but there are some virus that read the same part in two ways, with different offset, so the same part is interpreted as

  -JJJKKKLLLMMMNNN--

I don't remember if they use the other offset too

  --PPPQQQRRRSSSTTT-

[2] Another, not so interesting but relevant. Eukaryote has linear DNA, so they have some special repetition in the extremes. The idea is that the extremes are difficult to copy by the usual enzyme that copy the main part that has assorted code. But the extremes have a special easy pattern, so the cell can use some specialized enzyme to make them longer.

bashinator• 3 years ago

Nope, at best the filesystem is an analogy. Just like the stretchy rubber mat isn't a perfect description of spacetime.

anonymouskimmer9• 3 years ago

It needs a filesystem for the same reason they were invented for computers: to provide an impedance match between the upper layer semantics (a stream of pairs describing a protein) and the lower layer storage (blocks). Using block structured storage is more flexible in terms of being able to insert in the middle of a file, etc etc.

As a non-CS person I find this explanation opaque.

AllegedAlec• 3 years ago

https://xkcd.com/793/

fnordpiglet• 3 years ago

I for one welcome our new introner overlords.

MagicMoonlight• 3 years ago

That’s sneaky. Ironically more like a computer virus than the classical viruses. Taking over the host and modifying its boot partition so that it permanently gets produced by the system.

anonymouskimmer9• 3 years ago

There's basically no such thing as a boot partition. The machine of life has been turned on since the beginning. At this point, with all of the changes since the beginning, it's not obvious that there's a "boot partition" left that could reactivate life should it shut off. All cellular progeny is made with already functional and switched on proteins and RNA.

The best you get to shutting off (without permanent cell death) would be the computer equivalent of hibernation. All the proteins and RNA are still there just waiting for the signal to activate again.

jamiek88• 3 years ago

Crazy to think we are all here because of that first multi cellular organism splitting over and over and over.

Life doesn’t reboot as you say, it is split off from other organisms whether seed, sperm, rhizome or any other method it’s just cells dividing and spitting off other cells.

Mind boggling to me.

nobody9999• 3 years ago

The best you get to shutting off (without permanent cell death) would be the computer equivalent of hibernation. All the proteins and RNA are still there just waiting for the signal to activate again.

Fungal spores[0][1] come to mind.

[0] https://en.wikipedia.org/wiki/Spore#Fungi

[1] https://space.stackexchange.com/questions/37268/can-mushroom...

marcosdumay• 3 years ago

It was well known that a lot of our genome got inserted there by virus. I think the news this article is reporting is that the defense mechanism is the explanation for that weird behavior.

akavi• 3 years ago

I'd say more like a classical virus with a loop earlier in the central dogma.

Ie, in the DNA => RNA => Protein cycle, viruses are a loop from Protein => DNA or Protein => RNA. Introners are a loop from RNA => DNA.

gus_massa3• 3 years ago

Virus are not Protein => DNA or Protein => RNA. Their information is in DNA or RNA, so they are https://en.wikipedia.org/wiki/Virus#Genome_replication

* DNA => RNA => Protein

* RNA => Protein

* RNA => DNA => RNA => Protein

As far as I know, there is no method to do Protein => DNA or Protein => RNA at the celular level.

It would be very surprising. RNA and DNA are quite similar and have similar encoding, so RNA <==> DNA is a 1 to 1 translation.

The translation to RNA to proteins is not 1 to 1, and the translations table is quite arbitrary, so untranslating at the celular level looks extremely difficult.

sobkas• 3 years ago

That’s sneaky. Ironically more like a computer virus than the classical viruses. Taking over the host and modifying its boot partition so that it permanently gets produced by the system.

More like infecting compiler so every application build using it will include virus, including building compilers that will add virus code to their output and propagate it.

TeaBrain• 3 years ago

A fair amount of human DNA originated from viruses that infected our ancestors.

https://www.smithsonianmag.com/science-nature/virus-genes-hu...

masswerk• 3 years ago

"spliceosomes" – I'm somewhat disappointed. (Not really the true greco-roman spirit.)

fjfaase• 3 years ago

Bert Hubert has an interesting idea about the reasons for interons. He explains this in his talk 'DNA: More Greatest Hits (SHA2017)' The interesting bit, with some introduction, starts at: https://youtu.be/rCdhsN--Mdo?t=1440

This is a follow-up talk to his talk: 'DNA: The Code of Life' https://www.youtube.com/watch?v=EcGM_cNzQmE

neoyagami• 3 years ago

oh. a "descolada"

elevaet2• 3 years ago

Care to explain what you mean here?

koeng• 3 years ago

My favorite quote I saw or heard somewhere on the rogue genetic elements in us all:

“We are but a raft of genes in an ocean of retrotransposons”

A little hyperbolic, but dang there are a lot

stuckinhell• 3 years ago

Biology is truly fascinating, the ultimate hardware/software combo of proteins/genes.

It's likely parasites can alter our genetic expression and behavior today as well like rabies and toxoplasmosis(cats often have it). Rabies causing the fear of water is truly mind bending, how does it do that?!

Toxoplasma infection is classically associated with the frequency of schizophrenia, suicide attempts or "road rage". https://pubmed.ncbi.nlm.nih.gov/31980266/#:~:text=Toxoplasma....

Rabies:As the disease progresses, the person may experience delirium, abnormal behavior, hallucinations, hydrophobia (fear of water), and insomnia. https://www.cdc.gov/rabies/symptoms/index.html#:~:text=As%20....

whizzter• 3 years ago

Even more interesting reverse of that, hairworms that infect grasshoppers will once mature cause the hosts to jump into water and drown where the worm then reproduces before starting the cycle again.

hypertele-Xii• 3 years ago

And cordyceps fungi compel ants to climb to a specific height off ground, at millimeter and 95% accuracy, to a spot of ideal location and humidity for the fungus to spore.

And the craziest thing is, the cordyceps fungus doesn't actually infiltrate the ant's brain! Autopsies found the fungus spreads all over the ant's body, but not its brain!

thaumasiotes2• 3 years ago

Rabies causing the fear of water is truly mind bending, how does it do that?!

It doesn't.

Rabies:As the disease progresses, the person may experience delirium, abnormal behavior, hallucinations, hydrophobia (fear of water)

This is a weird mistake for the CDC to make. The etymological meaning of "hydrophobia" is "fear of water". But the English word is completely disconnected from that; it just means "rabies". Because of this, the disambiguation page for "Hydrophobia" on wikipedia links to rabies as well as to "aquaphobia", an actual fear of water which had to be named badly because the name "hydrophobia" was already taken.

Rabies was named "hydrophobia" because rabies patients will generally refuse water when it's offered to them. They do that because rabies makes it difficult to swallow, not because they're afraid of the water.

magpi3• 3 years ago

That is very interesting. In Chinese, a word for rabies is 恐水病, which literally means fear water disease. I have never understood why until I read your explanation, but from what you have said the Chinese term would also appear to be misleading.

vimax• 3 years ago

Have you watched a video of someone with rabies exposed to water? I don’t recommend it, it is more than a hard time swallowing.

livelielife• 3 years ago

is dna hardware? software?

it's both! it's neither! oh, and it's also the runtime!

borissk2• 3 years ago

The DNA code is software, the hardware and the runtime are RNA and proteins.

ramraj07• 3 years ago

It’s basically an ASIC.

mcv• 3 years ago

Evolution isn't very good at separating its concerns.

mmmrtl• 3 years ago

Misleading title ("Their" Genes). I don't see what introners have to do with the human genome?? They found evidence for introners in 5% of species...

Original paper: https://www.pnas.org/doi/10.1073/pnas.2209766119

elevaet2• 3 years ago

I might have missed it, but they didn't really discuss how introners replicate. Does the host species accidentally transcribe the intron segments into new introners until it evolves a mechanism to avoid that particular trick?

photochemsyn• 3 years ago

It's really just a proposal, there would have to be some associated enzyme that targets genes at the well-known splice site (maybe something like a CRISPR-related Cas etc. enzyme?)and inserts the intron sequence. This seems to date from this 2012 study:

"Birth of new spliceosomal introns in fungi by multiplication of introner-like elements (2012)"

https://pubmed.ncbi.nlm.nih.gov/22658596/

These are postulated to be relatively rare events, so catching one in the act would be difficult:

"However, dating of multiplication events showed that they degenerate in sequence and length within 100,000 years to eventually become indistinguishable from RSIs. We suggest that ILEs not only account for intron gains in six fungi but also in ancestral eukaryotes to give rise to most RSIs by a yet unknown multiplication mechanism." [ILE's being closely related intron sequences, RSIs being the regular jumbled-up types]

A DNA ‘parasite’ may have fragmented our genes

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