Borgs are giant extrachromosomal elements | Hacker News Reader

Borgs are giant extrachromosomal elements

biorxiv.org

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> Intriguingly, all Borgs carry large FtsZ-tubulin homologs that may be involved in membrane remodeling or division, and proteins that resemble Major Vault Proteins and the TEP1-like TROVE domain protein that also do not occur in Methanoperedens genomes (Table S5). These are known to form the highly conserved and enigmatic eukaryotic vault organelle, a ribonucleoprotein that has been suggested to be involved in multidrug resistance, nucleo-cytoplasmic transport, mRNA localization, and innate immunity.

I can't follow most of this, but the phrase "highly conserved and enigmatic eukaryotic vault organelle" jumped out at me: https://en.wikipedia.org/wiki/Vault_(organelle)

The vault complex is an amazing enigma I’ve been following since finding the name while browsing through some gene lists. Every cell in our body has this massive complex, it’s highly conserved and we have not a clue what it does.

Even weirder, according to that Wikipedia article, it doesn't appear to be necessary, or has very non-obvious implications when it's removed. Yet, it's present in almost all eucaryote cells...

The favorite nucleoprotein offspring of the ribosome elder gods shall not be disturbed in their nursery, lest a wrath beyond mere animo-younglings' understanding shall be unleashed.

Its well known what it does. The red pill activates it in 42% of all cells in your body and you wake up from your pod. Some people are known to surpass that threshold without taking a pill just reading HN comments. So be careful.

That is true for most things in the cell, though. There's an incredible amount of redundancy, optionality, and just plain unnecessary stuff. Vaults stick out because they're an apparently unnecessary thing that you can see down an electron microscope. There are many more equally unnecessary things that are just a lot smaller!

> and just plain unnecessary stuff

I'd like to point out that any protein that is produced takes up precious resources. Our evolutionary intuition suggests that unnecessary things should be dropped from the genome.

Suppose a protein is unnecessary. Then there would be no evolutionary pressure to keep it from mutating and loosing its function(and mutations happen all the time!). The organisms would just gradually loose it to mutations and we wouldn't find a conserved protein throughout eucaryotes. So there must be something keeping it.

Could it be a genetic parasite?

The genome is full of retrovirus remnants, so there’s a way for a parasite to piggyback on the host genome. Alu repeats in human genome are one such example. But there’s a hypothesis that these get “domesticated” by the genome and start serving a function.

One conserved over the whole tree of life? That's like imagining an editing bug that Emacs and Vim have both carefully and inexplicably preserved from the last universal common text editor.

"Although vaults have been observed in many eukaryotic species, a few species do not appear to have the ribonucleoprotein. These include:

Arabidopsis thaliana

Caenorhabditis elegans

Drosophila melanogaster

Saccharomyces cerevisiae"

Wow. As if some hacker is playing against the researchers, removing the backdoor from all the most studied systems.

What do those organisms have in common that made them good model organisms that researchers favoured studying? Perhaps one of those same properties (fast reproductive rate, maybe?) requires ditching the vault complex.

Plausible. Makes one wonder what else we haven't figured out because of the same bias.

Really insightful comment. Thanks!

Arabidopsis thaliana is at least interesting because it tells time https://youtu.be/CA-YsWXRSHU?t=418

It's possible, although the cited articles in that section are from 1990 and 1991. (Another one links to a clone of the same wikipedia article in pfam, which is a comically circular reference.) We hadn't sequenced much then, so the absence of these organelles was probably established by microscopy in these model organisms.

> Wow. As if some hacker is playing against the researchers, removing the backdoor from all the most studied systems.

Or perhaps it simply explains why it took so long to find them.

Anyone else stricken by how similar this looks to a flaggellar motor?

And, to my eye, not at all like a vaulted cathedral.

I'm completely in the dark when it comes to hard biotech, but have heard this labelled as a CRISPR-level development.

Based off this tweet[0] from one of the paper's authors.

Can anyone here confirm or deny this?

[0]: https://twitter.com/BanfieldJill/status/1414647658786922496

They found a bacteria with extra-genomic material that isn't in the shape of a plasmid (circular DNA that is a feature of bacterial transfection and gene transfer).

They believe it came from archean rather than bacterial sources. (Not really related, but many of our genes, and indeed one of our critical organelles, are also archea-derived, ie. the mitochondria.)

The genomic payload is large and comes with replication machinery (it might be a useful tool!)

Plasmids hold a much smaller payload than these units, and they're difficult to work with. Borgs are huge. If we can turn them into transfection toolkits, we can do larger scale genomic experiments much faster. That's extremely exciting.

Much of biochemistry research and understanding is done in bacteria. They're extremely useful little computers. We just discovered an extremely useful way to hack them.

In the wild, the gene payload codes for novel methane metabolic pathways. This also is of great interest. Not only for applicability to climate science, but also the natural ability to swap out or augment bacterial metabolism. Imagine all of the novel things you might swap in instead.

Who knows. These might wind up in eukaryotic cells too!

Noncircular extragenomic dna in bacteria isn't a new thing, for example, the marine algae cyanothece has linear DNA, and iirc it is important in regulating day/night cycles for nitrogen fixation (which is oxygen sensitive)

Wild stuff. Here's my current mental analogical model:

bacterium : animal :: computer : botnet

What do you mean?

You can often tell someone's age by whether or not they know analogies in this format. It used to be a staple of standardized testing on logical deduction.

A : B :: C : D

Is read as

A is to B as C is to D. The reader is meant to understand the relationship between A and B and how it's similar to the relationship between C and D.

An easy one might be,

basketball : hoop :: hockey puck : net

But they can get quite challenging. And with multiple choice answers present in standardized testing, you often have to understand the complex relationships between many abstract concepts, and evaluate that the abstractions are of a similar type or degree.

They're actually kind of fun.

Here's an example taken from [1] (the source also has excellent discussion as to why they were removed) :

PALTRY : SIGNIFICANCE ::

  A. redundant : discussion
  B. austere : landscape
  C. opulent : wealth
  D. oblique : familiarity
  E. banal : originality

Pick the correct answer A-E.

[1] https://blog.prepscholar.com/sat-analogies-and-comparisons-w...

Is this an age thing?

I’ve been surprised a number of times by people not being familiar with this format, but they were only a year or 2 younger than me. (I’m 25)

It’s a nice format for thinking about things, so if people stopped learning it, that seems unfortunate to me.

May also be an American thing (at least the whole spending a lot of time on analogies for SAT testing thing)

For what it's worth I'm a 25-year-old Australian who never encountered this specific syntax in schooling (it was always phrased "as <x> is to what?"), but am still very familiar with it from general interactions online.

It's probably just a matter of how strongly your immediate social circle feels about formal logic.

As one data point, we never did these sort of analogy puzzles in school in Finland (but we don't have standardized multiple-choice testing either). I'm only familiar with the concept and format as a part of the general anglosphere meme complex that you naturally get exposed to if you spend time on the internet.

I just assume I'm overly familiar with it as someone who was a natural test-taker. (Early 30s)

A better analogy might be

bacterium : animal :: raspberry pi : kubernetes cluster

Fantastically written summary, thank you!!

I didn’t quite get the climate science impact. Is the suggestion that these borgs currently are “digesting” methane, and therefore helping reduce the amount of methane released to the atmosphere? Is there a suggestion that we might augment them to “digest” CO2 too?

Methane is a more harmful greenhouse gas than CO2

Plasmids are an absolute doddle to work with. Borgs are huge, which makes them a nightmare to work with.

I used to work with bacterial artificial chromosomes (BACs) that were ~100 kb in size, and those were already a pain. You have to be really delicate when preparing the DNA because it's so easy to shear. You can't separate it on a normal gel, you have to use PFGE. Borgs will be even worse.

Borgs being bigger means you can fit more interesting stuff into them. But i don't know to what extent that is a constraint at the moment. 100 kb is already a lot of space for bacteria!

Bacteria and eukaryotes are different enough that we won't find borgs themselves in eukaryotes, and if you put a borg into a eukaryote, it wouldn't replicate. However, they could be used as a vector for constructing human artificial chromosomes - you need something that replicates in working organism, like bacteria or yeast, so you can do the molecular biology, and you add the necessary human sequences to that:

https://www.nature.com/articles/gt2009102

At the moment, the biggest vectors we have are yeast artificial chromosomes, which i think top out at ~1 Mb.

But again, what are you going to do that needs that much space? A typical human gene is a few tens of kb; 40 kb is big (there are megabase freaks, but they are very rare). And that's for the gene, introns and all - often you can use a cDNA which is a fraction of the size.

> (Not really related, but many of our genes, and indeed one of our critical organelles, are also archea-derived, ie. the mitochondria.)

Mitochondria are related to Rickettsia, which is a bacteria.

I don't think it is as big a discovery as CRISPR. These are very cool, but in a basic science sort of way. The unknown proteins may be massively useful for methane processing, but no one knows that at this point. There are similar, although much smaller, genetic elements such as plasmids and BACs which could fill a similar role anyway.

I don't see what could make this a really big deal outside microbiology yet. But maybe someone else will see what I am missing.

"Sets of three or more perfect tandem direct repeats (TDR) are a characteristic feature of the Borg genomes" is not something I ever expected to read in a biology paper.

Kudos to Elliot Smith mentioned in the paper for proposing the name. I hope that any resistance for it to become accepted term in biological sciences will be futile.

(The pedant in me wants to say, these elements should be called nanoprobes; a Borg is the thing you become when you let the small things get into your bloodstream.)

I’m surprised that no one commented on the bacterium in question isn’t strictly bacteria. They’re from Archean domain of life, which is a highly diverse class of bacteria like species. Archaeons are like weird mashups of eukaryota and bacteria with properties shared between them. This separation wasn’t known until fairly recently (70s), so it may not be familiar to most. They’re really cool lil bugs!

Can someone ELI5? What is this about and why is it a big deal?

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