The role of eccDNA in cancer is not a particularly new concept. However, studies like this are important to further elucidate cancer-promoting mechanisms.
Additionally, the use of artificial eccDNA holds a lot of promise for genetic enhancement in many forms of life from humans, to livestock, to plants.
Essentially, we could create artificial chromosomes which express useful genes or have inverted repeats which deliver siRNA to silence other genes and viruses.
Similar to plasmids, except would have much larger payloads and ideally a heritable mechanism, perhaps by tethering against native chromosomes via zinc fingers, viral-encoded protein, or AT-hook motifs.
So these things interfere with genetic operations in the cell, including cancerous cells. There's some evidence linked showing they enhance cancer treatments. Radiotherapy works by inducing cell and DNA damage in cancer cells, and these siDNA hurt their ability to repair themselves.
Circular strands of DNA that live outside the chromosome which are those X and Y things, a condensed form of DNA. Like a little DNA module floating about in the cell. What if you could develop new modules and deliver them to people's cells via viruses or something?
Some of its friends died, releasing useful plasmids into the environment? They'll just absorb it. They're like the Mega Men of microbiology. Things die and they absorb their powers.
Virus infects bacteria and adds its genetic material to it to make it produce copies. Those copies end up carrying some bacterial DNA in them though. This leads to some viruses turning into a DNA injection mechanism that transfer plasmids to other bacteria. Perhaps scientists will figure out how to use them to deliver DNA to our cells instead.
Regarding plasmids, there is a similar mechanism of DNA exchange in human cells known as "gypsy transposons," that are viral fragments which were partially integrated into germline ancestry.
> An endogenous retrovirus is a retrovirus without virus pathogenic effects that has been integrated into the host genome by inserting their inheritable genetic information into cells that can be passed onto the next generation like a retrotransposon.
> When the retroviral DNA is integrated into the host genome they evolve into endogenous retroviruses that influence eukaryotic genomes.
I read recently that DNA transcription for protein expression is able to identify and skip an inserted element, but that the protein will be slightly different at the boundaries.
It appears to have gone badly wrong for the "Tasmanian Devil."
Yeah, status seeking by using uncommon words or concepts, often noticeable in geek-culture. The same thing occurs in many cultures. “Well-educated” people in England might use more sophisticated[1] language and drop[2] references in Greek, Latin, or other languages of le très bien formées. “Elucidate” feels like a status signal in the OP’s comment.
Personally one has been working on counter-signalling[3] by using simpler words and concepts, although one cannot say one is succeeding.
[0] They go on to elucidate. Apparently if you… play strategy s* = ( s*, s*M, s*) where s* < s*M. Let μ describe beliefs that are Bayes consistent with playing s*. Then the expected gross payoff to sender q from signal s*M is Eμ[q´|s*M,q] = M … Yup, they rather lost me at that point.
Exactly the point: well-educated people use words that appear in scientific papers. Showing you are well-educated is a common status signal amongst many well-educated people.
Some people are lingual chameleons[1]: their language patterns completely change depending on their social surroundings. And many people are liguistic artistes[2] who choose their language to paint an image of themselves.
Well-educated people use more precise language than the average person.
Otoh, the article uses words like roly-poly and willy-nilly, which I found jarring in the context of a moderately technical article from Stanford Medical.
You are right. In the same issue there is also a paper from Andreas Beyer’s team on the effects of aging on faster error-prone transcription in several species.
Age-related difference (interpreted naturally as transcription errors) cut out the wrong pieces of precursor mRNAs and this can lead to RNAs and circular RNAs in the cytoplasm. Not to mention strange mRNA isoforms. Probably not a good thing.
K. Mozhui and others have shown an increase is epigenetic noise with age in mice and there is similar work in “wild” human cohorts.
But the key questions in all of this work are—-What is causal? What is just consequence?
The multiple flows of causality is a very tricky problem. Genetic variants are the most obvious candidates once environmental factors (radiation exposure, toxins, diet) are reduced or standardized in a well controlled laboratory environment.
Because they aren’t under the same selective pressure as normal chromosomes, the number of ecDNA molecules can be highly variable between daughter cells. This is one of the potential resistance mechanisms for a tumor. If you have a drug that targets a gene in the ecDNA, the tumor could only keep clones with a small number of ecDNAs during treatment. Then after the drug has cleared, the number of ecDNAs can then rise again.
When you lose the default 2 copy state, natural selection can follow non-Mendelian patterns.
Cre-lox recombination is effectively payload-unlimited. Why create an artificial chromosome when inheritance is intended when you can just add to a current chromosome?
> perhaps by tethering against native chromosomes via zinc fingers, viral-encoded protein, or AT-hook motifs.
It sounds complex. Partition loci would be sufficient for inheritance in both offspring cells.
Highly variable. In cancers they can be much larger. Mitochondrial circular DNA is about 16,600 basepairs. In comparison, in the paper below one example of a cancer-driven ecDNA is 1,260,000 basepairs (EGFRvIII). ecDNA were originally detected using cytogenetic light microscopic methods, hence the original bias toward large size.
> Extrachromosomal circular DNA is derived from chromosomal DNA, can range in size from 50 base pairs to several mega-base pairs in length, and can encode regulatory elements and full-length genes. eccDNA has been observed in various eukaryotic species[2][3][4][5][6][7][8] and it is proposed to be a byproduct of programmed DNA recombination events, such as V(D)J recombination.
There are basically two ways to keep DNA from degrading in the cell: protect the ends with special proteins or DNA structures, or make it so that there are no ends to protect by having the DNA be circular.
I used chatgpt and it mentioned a plant called the mayapple that contains an ecdna inhibitor called podophyllotoxin. The semi synthetic derivative is Etoposide. Also it mentioned Cisplatin as another ecdna inhibitor.
if you are a cancer researcher, please share research assumptions that are debunked yet still commonly held.
i’m compiling a list.
these must be empirically supported.
for instance, i believe negative conclusions based on knockout studies are misleading, but this is not empirically proven and would not qualify. (if you knock out a fire alarm and the house still functions, saying the alarm serves no purpose is flawed.)
Levin, M. (2021), "Bioelectric Signaling: Reprogrammable Circuits Underlying Embryogenesis, Regeneration, and Cancer", Cell [1] is a general overview how cancer is a breakdown in communications leading to a down-scale of the self for the affected cell, see also Levin, M. (2021), "Bioelectrical approaches to cancer as a problem of the scaling of the cellular self", Progress in Biophysics and Molecular Biology [2]; for more articles [3].
In video format: "Why don't (today's) Robots get Cancer" [4]
A knock-out study will work as well as the precise definition and measurement of the phenotype you're looking for will allow. The point you're making is well understood by geneticist. There's about 22K genes in the genome, if your typical genetic screen returns a list of a 0 to 1K positives, no one is claiming that the 21K genes are absolutely uninvolved in the phenotype.
I completely agree there are many flawed scientific papers in general. I am wondering about your specific category of flawed papers.
Could you point to one concrete example where you believe a paper is flawed in its conclusion, where they've claimed a gene has no function in a pathway under the given experimental conditions, after performing a knockout?
because the papers seemed invalid, i didn't save them. i'll try to find them.
even if i share a few, it's possible most papers do not commit this mistake, and i was simply unlucky to stumble upon a few and generalized from an invalid sample size.
which is why i disqualified the opinion by saying it was not empirically supported.
for what it's worth, i discussed this opinion beforehand with several post-docs from respected schools and did not get pushback. this isn't proof either, but merely clarifies that the comment wasn't a thoughtless one.
in the meantime, do you mind sharing one widespread assumption you believe is false? it sounds like you're very informed, so it would be great to learn from you.
Additionally, the use of artificial eccDNA holds a lot of promise for genetic enhancement in many forms of life from humans, to livestock, to plants.
Essentially, we could create artificial chromosomes which express useful genes or have inverted repeats which deliver siRNA to silence other genes and viruses.
Similar to plasmids, except would have much larger payloads and ideally a heritable mechanism, perhaps by tethering against native chromosomes via zinc fingers, viral-encoded protein, or AT-hook motifs.