[HN Gopher] 'Obelisks': New Class of Life Has Been Found in Huma...
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'Obelisks': New Class of Life Has Been Found in Human Digestive
System
Author : unkeen
Score : 270 points
Date : 2024-12-30 08:12 UTC (14 hours ago)
(HTM) web link (www.sciencealert.com)
(TXT) w3m dump (www.sciencealert.com)
| asymmetric wrote:
| The study hasn't been peer reviewed yet, so the title is a bit
| too confident in its claim.
| robertlagrant wrote:
| Maybe Obelisks need an asterisk until peer review?
| fecal_henge wrote:
| Splendido.
| lifeisstillgood wrote:
| We should not be so dogmatix in requiring scientific protocol
| - maybe there are some VitalStatistix we are not yet aware
| of.
| readthenotes1 wrote:
| In case others don't get it:
|
| https://asterix.com/en/portfolio/obelix/
| moralestapia wrote:
| Here's the journal publication (which came later during the
| year):
|
| https://www.cell.com/cell/abstract/S0092-8674(24)01091-2
|
| It truly is a new class of genomic elements.
| kelseyfrog wrote:
| And it's been replicated?
| moralestapia wrote:
| It's using data from the Integrative Human Microbiome
| Project [1], so, in a sense, hundreds of high-quality
| biological replicas support their findings. Obelisks were
| found in a substantial portion of them.
|
| They then expanded the search to millions of sequences,
| which are publicly available, and found ~30k different
| classes(!) of Obelisk elements. One could argue that the
| quality of each of these "experiments" may not be as good
| as IHMP, but still, the signal is more than sufficient to
| clearly demonstrate the existence and implied significance
| of these elements.
|
| 1: https://pubmed.ncbi.nlm.nih.gov/31142853/
| tokai wrote:
| Peer review doesn't do what you think it does.
| dr_dshiv wrote:
| Remnant of RNA world?
| ababaian wrote:
| Aren't we all?
| dbcooper wrote:
| Article is from January. Has the study now been published in a
| journal?
| magicalhippo wrote:
| Yes, the bioRxiv entry[1] links to Cell[2].
|
| [1]:
| https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1
|
| [2]: http://dx.doi.org/10.1016/j.cell.2024.09.033
| Thoreandan wrote:
| From one of the paper's authors elsewhere in this thread:
| https://www.cell.com/cell/abstract/S0092-8674(24)01091-2
| andybak wrote:
| > researchers have stumbled across what seem to be an entire new
| class of virus-like objects.
|
| I was confused at first. This isn't "Class" in the technical
| sense (i.e. the level between Phylum and Order)
| digging wrote:
| For me it was not confusing; I don't think a newly discovered
| taxonomic Class would make mainstream news. I was expecting
| something higher-order and the discovery delivered!
| ababaian wrote:
| Cool :) I'm a co-author on this. AMA.
|
| This is now a peer-reviewed paper, published last month in Cell
| [https://www.cell.com/cell/fulltext/S0092-8674(24)01091-2].
|
| Obelisks are part of a larger research program we're developing
| at the University of Toronto + collaborators, see also: Virus-
| Viroid Hybrids paper
| [https://www.nature.com/articles/s41467-023-38301-2] and the
| Zeta-Elements
| [https://www.nature.com/articles/s41586-021-04332-2].
|
| Computational biology is driving a revolutionary expansion of our
| understanding of Earth's biodiversity. I believe Zeta-elements,
| Ambiviruses, and Obelisks are just the beginning. If you're
| interested, our "Laboratory for RNA-Based Lifeforms" (University
| of Toronto) is hiring passionate developers/post-docs/graduate
| students [https://www.rnalab.ca].
|
| Edit: OK going to call it for now. I'll check in later today if
| there's any outstanding questions.
| Traubenfuchs wrote:
| How do obelisks fit in with commonly known forms of life?
|
| We all understand cells/bacteria and their interaction with
| viruses: Viruses infect cells and make them into virus
| factories...
|
| What do obelisks do? Are they integrated / read by DNA
| machinery/organells into cells that then produce more obelisks?
|
| What's their life cycle?
|
| How are they different from alread known viroids?
| ababaian wrote:
| Largely we don't know. That's what makes them cool. This
| opens up a fairly large debate about where you draw the
| boundary of "life", "organisms", and "entities". It's a fun
| debate to have over a few beers since there is no objective
| correct answer.
|
| My view is that Obelisks are more like Viruses or Viroids, or
| some kind of mobile genetic element. The key detail is that
| they appear to be strictly RNA elements (they don't have a
| DNA counterpart). So they're most likely using host RNA
| transcription machinery to make more copies of themselves,
| this is what viroids and satellite viruses like "Hepatitis
| Delta Virus" do.
|
| What do they do? Well that's the right question. My guess is
| the kinds of things that bacteriophages do, Obelisks do too.
| Exploit cells to make more copies of themselves as selfish
| replicators.
| bicx wrote:
| Is it possible that these may cause diseases that
| previously went unexplained?
| ababaian wrote:
| It's possible, yes. But right now there is no evidence
| for Obelisks being linked to any disease, not even a
| phenotype in the cells carrying them. Keep in mind also
| that these elements likely interact with bacterial cells,
| so effects on human disease would most likely be
| indirect.
| lukeschlather wrote:
| Is there really any evidence that they are parasites and
| not part of the host's machinery?
| ababaian wrote:
| These are two distinct questions. Are Obelisks part of
| the self? If you think of the "host" as being made up by
| it's DNA, then these are not part of that set, since they
| are not found in DNA copies. Or is an organism it's RNA?
| If it's the RNA that's the organism, then sure you could
| say this is part of that organism in that it exist as
| organelles of sorts, like mitochondria or chloroplasts
| (but in RNA form).
|
| The second question is if it's parasitic, mutualistic, or
| neutral. If it's a parasite it should cause a fitness
| defect to the DNA organism's replication. As of yet I
| haven't seen evidence of this at the cellular level. But
| there is a strong argument that by depleting cells of
| nucleic acids (RNA) would have to be at least minimally
| parasitic. That is of course unless they confer some
| advantage to the cells with Obelisks. In which case, why
| don't all microbial cells have Obelisks. Importantly, the
| relationships between all the various Obelisks at least
| for now, is not lining up with microbial genome
| evolution. This would mean they are jumping from genome
| to genome.
|
| Now you're in a late night pub discussion about where we
| should be drawing the boundaries of life.
| brokensegue wrote:
| I'm unclear why we are calling these a new class of life
| rather than just a new kind of virus. Their shape?
| ababaian wrote:
| I think this is the journalist playing at the idea that
| we don't have a universally accepted definitions of
| "life", "virus", "viroids", "mobile genetic elements",
| "plasmids", or the other words that describe what I view
| as the agents of evolutionary games. It is kind of catchy
| way to raise that conversation though eh!
| stainablesteel wrote:
| in simple terms, it seems these are just rod-shaped RNA
| plasmids that encode a couple proteins and exist without any
| kind of membrane or coating, does that seem right? is it that
| elucidated?
| ababaian wrote:
| Sure, in a redutionistic sense. In the same light "Hepatitis
| Delta Virus" is an RNA plasmid, yet it causes liver cancer in
| humans. I err on the side that the simplicity of the genetic
| system should not deceive us into thinking it's trivial. The
| next 12 months of discoveries is what makes this so exciting.
| bryan0 wrote:
| Hey this looks pretty amazing, congrats on the research. The
| article doesn't seem to explain much though and the papers are
| pay-walled(?) so my question is how were these discovered only
| now and not noticed before?
| ababaian wrote:
| There are preprints for all the papers [https://www.biorxiv.o
| rg/content/10.1101/2024.01.20.576352v1], they're
| operationally the same.
|
| How were they not noticed before? Well that's how science
| works. Someone eventually has to be the one to notice
| something is going on right?
|
| I think it's a common fallacy that we, as a species, are not
| ignorant to the complexity of Nature. The hardest part is to
| see it.
| DoctorOetker wrote:
| Consider the existence of forensic genetic polymer tagging
| sprays etc.
|
| For example: https://www.selectadna.co.uk/dna-tagging-spray
|
| One could easily fathom not just overt authorities but also
| covert authorities wishing to use similar technology.
|
| Clearly an intelligence agency doesn't want the lower level
| police leaking detections of higher importance, so best to
| differentiate say DNA for cops and RNA for intelligence
| services, so that the pragmatic tools and workflows of
| police won't result in uncleared personnel figuring out
| things they aren't cleared for.
|
| That wouldn't explain quasi biological statistics as
| opposed to white noise random sequences, which would
| suffice for tracking, but also would blow the cover as a
| man-made genome...
|
| I.e. if RNA sprays had been reserved by some power bloc for
| intelligence service purposes (DNA sprays for usual law
| enforcement), then there is a clear incentive to have the
| secret pseudorandom sequences at least mimic plausible
| biology sequences, an adversary bloc detecting such a
| tracker might believe the sequence to be of biological
| origin, and intelligence associated academics would publish
| it: revealing both the detection by an adversary bloc and
| the academic's employment by intelligence circles...
| layer8 wrote:
| I would expect that you still need to have _some_
| substantial expertise to have any idea of what you are
| doing, and to know that what you are doing makes sense and
| also hasn't been done yet. Someone unfamiliar with
| molecular biology would likely need to invest some time to
| get up to speed.
| andrewflnr wrote:
| Do you have any clear idea yet what the proteins do that the
| obelisks code for?
| ababaian wrote:
| No clear ideas. But I would not be surprised if a dozen labs
| have jumped at the chance of trying to figure it out. So wait
| a year and ask again.
|
| Edit: Or better yet, try and figure it out for yourself. The
| tools to do this analysis are available to everyone.
| promptdaddy wrote:
| What are these tools you speak of ?
| ababaian wrote:
| The most limiting is our own imaginations. For the nuts
| and bolts: a class of really engaged and brilliant
| students at UofT recently documented the tools and
| methodology to go about characterizing Obelisks
| [https://github.com/ababaian/VIRUSxDISCVRY].
| andrewflnr wrote:
| Dude, I already have _way_ too many projects. I 'm going to
| wait for the experts on this one. :D
| ababaian wrote:
| There's literally no experts on the subject.
| dotancohen wrote:
| I think that GP means biologists. Biologists may not be
| experts on obelisks, but they have the base knowledge to
| understand many of the mechanisms and concepts.
| ababaian wrote:
| I understood as much. My point is that it's not clear to
| me that it will be a biologist, and not a
| statistician/mathematician, or developer/data-scientist
| that will be the one to sufficiently find the solution.
| There are literally petabytes of public data which
| already hold the answer. We now have to accept a
| different paradigm by which we can do biology, and
| biologists are not always the best equipped for this
| paradigm.
| dotancohen wrote:
| That is extraordinarily insightful, thank you.
|
| Maybe I will give this a crack. If I get anywhere I'll
| contact a local university to speak to a biologist.
|
| Thank you.
| Balgair wrote:
| @ababaian. You may want to put your contact info in your
| bio here, based on your comments and responses. It may be
| helpful for others to find you an contact you if they
| ever see anything. Check if they're not seeing ghosts in
| the data
| marojejian wrote:
| >Obelisks form their own phylogenetic group without detectable
| similarity to known biological agents.
|
| ababaian, does this truly mean no similarity to any other
| sequences, even virus/viroid?
|
| That seems very exciting, since my understanding is that we see
| a lot of conservation within the known branches of life, and
| don't discover new ones often!
|
| Though perhaps it's more common to find totally novel
| virus/viroids? How often do we find truly novel biological
| agents at the sequence level?
| ababaian wrote:
| To the limits of where our understanding of how "entities"
| are connected to one another (homology). Yes, there's nothing
| like them. You could make an argument they are "viroid-like"
| and there's a deeper evolutionary connection between
| viroids/viruses/plasmids, but the information theory to
| formally establish such a connection is not sufficiently
| developed. It's a worthy scientific problem!
|
| Is it common to find new viruses/viroids/biological agents?
| Well it certainly is starting to feel that way to me.
| DoctorOetker wrote:
| > You could make an argument they are "viroid-like" and
| there's a deeper evolutionary connection between
| viroids/viruses/plasmids, but the information theory to
| formally establish such a connection is not sufficiently
| developed.
|
| The way it is phrased, _insufficiently developed
| information theory_ is rather surprising. Did you mean to
| write that not enough genome data has been collected to
| formally establish a link, or are you actually stating that
| we have all the data but as a species have not sufficiently
| developed the _mathematical subdiscipline of probability,
| information theory_ ?
|
| I could follow the first, but the latter?
|
| EDIT: I now believe you meant neither but more something
| along the lines of: we probably have plenty of data, and
| usual information theory should suffice, but we simply
| havent exhaustively applied the tools to collate the
| information and make the implicitly available data more
| explicitly manifest.
| ababaian wrote:
| We certainly have the data, too much so actually. I
| should correct the statement to say, we have
| insufficiently developed _applied_ information theory.
|
| We know how to quantify homology, it just has not been
| applied to sufficient depth to the field of RNA/viroid
| evolution to resolve how much of an RNA element with
| extensive secondary structure, or ribozyme is evidence of
| a homology vs. convergence. And how could we resolve the
| two? It's easy with protein sequences, tricky with
| protein structures, but deep RNA evolution? That's a
| mystery.
| Sxubas wrote:
| Thanks for your work on the research. I get a feeling of
| amusement and wandering when thinking on what functions the
| obelisks may have.
|
| I am hopeful this discovery can lead to technology to improve
| people's life. Just thinking out loud, cancer treatments,
| orphan diseases treatment, prevent Alzheimer's progression, new
| vaccines.
|
| Very long shots, but that's the beauty of unknowns. I'm highly
| jealous of scientists that will formulate and test hypothesis
| around this topic.
| ababaian wrote:
| Everyday I get to do this kind of research, I'm grateful to
| be the one doing it.
| yawnxyz wrote:
| Are there more of these undetected/undetectable entities out
| there?
|
| E.g. are there more "life" like obelisks and similar out there
| in genome samples?
| ababaian wrote:
| I should certainly hope so.
| ceejayoz wrote:
| Probably. This is a good illustration of just how hard it may
| be to conclusively find life on other worlds; we don't even
| know what exists here on Earth yet.
| aaroninsf wrote:
| This is basically the core plot device (and foregrounded
| assertion, for its ramifications) of a recent scifi book,
| which for spoiler reasons I rot13:
|
| Xvz Fgnayrl Ebovafba'f Nheben
| light_hue_1 wrote:
| The reason these things are so hard to find on Earth is
| because it's teeming with other life. If it wasn't and
| these things were isolated on Mars it would be relatively
| easy.
| throwup238 wrote:
| Probably. There's a whole category of organisms that can't
| cultured in a lab or effectively studied called microbial
| dark matter:
| https://en.m.wikipedia.org/wiki/Microbial_dark_matter
|
| These kinds of DNA and RNA studies are the only ones that can
| realistically pick up evidence of these organisms outside of
| an extraordinarily lucky electron microscope slide.
| ababaian wrote:
| If you want the real mind-trip, try to think about how
| little we know about detecting "life" that is not based on
| nucleic acids.
| hinkley wrote:
| There's a biological detective story out there about
| someone figuring out how to culture the black soot near
| distilleries. This isn't the version I read but it's the
| same microbe:
|
| https://www.wanderingspiritsglobal.com/whisky-fungus-
| baudoin...
|
| It doesn't culture in agar. Unless you add alcohol to the
| Petri dish and then it does. Things like this are why I
| still have my fingers crossed that we will have one or more
| helicobacter pylori (the bacteria that causes 90% of
| ulcers) moments for intestinal ailments. These obelisks may
| turn out to be one of them, and understanding could lead to
| better treatments and prevention.
| casenmgreen wrote:
| Don't know. They're undetected =-)
| pseudosudoer wrote:
| Any chance there is a correlation between Obelisks and
| autoimmune diseases?
| ababaian wrote:
| Not that I know of, although this doesn't mean it isn't
| happening, it's something which has to be investigated in
| detail.
| RobotToaster wrote:
| Can we kill them? Do we know if any drugs have anti-obelisk
| effects?
| ababaian wrote:
| What have Obelisks ever done to you? Our first reaction
| shouldn't be to kill everything we don't understand :'(
|
| Good pragmatic question though. It's not clear if any drugs
| up- or down-regulate Obelisk genome copy, you could re-
| investigate other drug-treatment studies to see if Obelisks
| incidentally present are altered and get an "accidental"
| study.
|
| From a molecular perspective, the most likely compounds and
| methods would be those which work against viroid replication
| (i.e. RNA polymerase inhibitors, translational inhibitors,
| CRISPR,...). You just have to maintain a preferential
| toxicity to Obelisks over host cells.
| hinkley wrote:
| Well, you say they aren't linked to IBS or Crohn's, but
| there's a difference between proving that they don't all
| cause intestinal issues and eliminating every strain as a
| cause. It's kind of embarrassing how recently h pylori was
| caught red handed.
|
| Some people carry staph on their skin their whole life and
| never end up with a lesion.
| ghostly_s wrote:
| I'm not gleaning what observations support these things being
| alive from the article-how do we know they're not just an odd
| form of garbage RNA produced by cells?
| ababaian wrote:
| That's exactly what they are though, some piece of garbage
| RNA cells are producing. A lot of things meet that definition
| if you think about it.
| aaroninsf wrote:
| This is by a good margin the most interesting knowledge-domain
| I have encountered in at minimum weeks. Super-interesting.
|
| Hammerhead Self-Cleaving Ribozyme is quite a chunk of English.
| kettleballroll wrote:
| How did you find these things? Since you "stumbled upon them",
| you probably didn't know what you eee looking for, so... How
| did this research get started?
| mmooss wrote:
| The OP addresses it to some degree, but how does this fit with
| the fundamental classes of phylogeny?
|
| My poor understanding has been that there are cellular
| organisms / 'biota' (if those are the right terms -
| prokaryotes, eukaryotes, etc.) and viruses. Where do obelisks,
| Virus-Viroid Hybrids, Zeta-Elements, Ambiviruses all fit in
| that scheme, if they do at all? Or is there a new scheme?
|
| And it is very cool for you to answer questions here. Remember
| us if you visit Sweden someday! :)
| ababaian wrote:
| The classic phylogenetic classes are a fantastic model, but
| https://en.wikipedia.org/wiki/All_models_are_wrong :)
|
| Phylogeny is the study by which things relate to one another.
| There is a divergence point at which point it becomes
| impossible to relate two sequences to one another. Obelisks,
| Zeta-Elements, Deltaviruses, viroids all veer towards their
| own divergence point into infinity, but their are higher-
| order genome organization traits which are consistent. We
| don't know if these traits are the same by origin, or the
| same by chance. Interestingly Ambiviruses also have this
| genome organization, but they have a protein which is de
| facto of an RNA virus.
|
| My opinion is that these simple genome layouts (structured
| circular RNA elements with ribozymes) are like a cauldron of
| mixing simple genes, and when they come together just the
| right way, we see those lineages take off. Think of it as an
| ocean of ancient primordial RNA replicators, ready to fire
| off, and this process is ongoing even today.
| mmooss wrote:
| Thank you.
|
| > The classic phylogenetic classes are a fantastic model,
| but https://en.wikipedia.org/wiki/All_models_are_wrong :)
|
| For the record, yes, I know. Unfortunately, we need models
| to organize the world in our limited brains, and the less
| intimate experience one has of something, the more
| simplified their model. This isn't my day job! :)
| endofreach wrote:
| Serious question, super OT but i've wanted to ask this someone
| who works non-trivial fields like you for a long time: Have you
| ever used a LLM for something relevant to your work?
| ababaian wrote:
| It's not OT at all. It depends on what you mean exactly by
| LLM, but we use them all the time. ESMFold2 was an LLM
| [https://www.science.org/doi/10.1126/science.ade2574] and was
| instrumental in advancing deep protein fold prediction in
| metagenomic space. Likewise AlphaFold2 it's direct
| application in creating FoldSeek for ultra-deep homology
| search. Both of these actually have radically improved our
| capacity to say Obelisks are _REALLY_ not like anything
| that's known.
|
| Besides that I encourage all students to use ChatGPT for
| research, coding, copy editing, etc... I haven't encountered
| an LLM that can deal with difficult domain problems like
| we're facing, but I'd welcome the help. I'm for using all
| tools available, my main criticism with AI/LLM in general is
| the poor way in which uncertainty is reported.
| Communitivity wrote:
| This is fascinating work and sounds a little like the research
| my daughter says she wants to study (she's only a sophomore at
| UMBC right now, though). She hopes to get an internship in the
| summer of her junior year. She is interested in plant biology
| and bioengineering.
|
| If I understand correctly, plants have RNA - would this mean
| new RNA-based lifeforms could also be found within plants?
| light_hue_1 wrote:
| There are no RNA-based lifeforms. All known life is DNA based
| but uses RNA internally. The earliest common ancestor of all
| life was DNA based, LUCA
| https://en.wikipedia.org/wiki/Last_universal_common_ancestor
|
| There is a hypothesis that once upon a time life passed
| though an RNA only stage without DNA and proteins. RNA world
| https://en.wikipedia.org/wiki/RNA_world
| lolinder wrote:
| The premise of TFA is that we're treating viruses and
| virus-like things as a class of lifeform. There _are_ RNA
| viruses, and these obelisk things are also RNA-based.
| Presumably that 's what OP is asking about with regard to
| RNA-based lifeforms.
| ababaian wrote:
| I like to view it that we're all RNA-based lifeforms.
| Operationally: DNA, RNA, or other are just a vehicles which
| hold our information.
|
| This podcast RadioLab with Carl Zimmer (11m) I think
| captures the essence of the idea near perfectly:
| https://radiolab.org/podcast/creation-translation
| ucha wrote:
| Does this support the Selfish Gene theory of Richard Dawkins?
| They look like the smallest self-replicating molecules that he
| mentions in the beginning of the book.
| ababaian wrote:
| Absolutely, reading Selfish Gene in high school set me on the
| path to this type of exploration. Genes, in the pure abstract
| sense, are the unit by which we interrogate understand
| evolutionary change. There's a large grey area about the
| boundaries of genes, but after a certain point, genes
| assemble into operational units larger than themselves, a
| genome. Obelisks are some of the simplest, most rudimentary
| genomes described thus far.
| dj_gitmo wrote:
| How did you come up with the name? And is the "Oblin" protein
| is named after Obelisks?
| casenmgreen wrote:
| Privacy policy / cookie dialogue on that page is class A scum-
| worthy dark pattern.
| casenmgreen wrote:
| This is a staggering and amazing finding.
| kylehotchkiss wrote:
| But how are these life? Life generally defined by ability to
| reproduce and these would be piggybacking on hosts cellular
| machinery.
|
| Do these have a known utility or is it possible some junk DNA is
| involved with their encoding?
| joe_the_user wrote:
| My crude understanding is the definition of life has gotten
| quite fuzzy in current biological theory.
|
| Notably, I think the "viruses first" theory for the origin life
| has gained force. This says that first came protein/DNA soup,
| then came viruses and only then came cellular organisms.
|
| And if you want something that doesn't "piggyback", you'd have
| to wait for photosynthesizing plants and that's several steps
| further in evolution (in my layman's understanding of current
| theory).
| treprinum wrote:
| I am really glad we are finding new pieces of the puzzle of how
| our gut works and perhaps can someday understand their effect on
| immunity, neuro-degeneration, cancer etc. for which we now only
| have accidental findings.
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