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The role of eccDNA in cancer is not a particularly new concept. However, studies like this are important to further elucidate cancer-promoting mechanisms. Addi

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.

jtbayly 3y ago
Reading this gives me an understanding for how some of my friends feel when I talk about technology. “Make sure to set the dip switches on your SCSI drive and confirm your cable is USB 4+ PD.” Lol
- matheusmoreira 3y ago
  English Wikipedia is a surprisingly good resource. https://en.wikipedia.org/wiki/SiDNA https://en.wikipedia.org/wiki/SiDNA 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. https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA 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? Bacteria already have this capability - and more. https://en.wikipedia.org/wiki/Transformation_(genetics) https://en.wikipedia.org/wiki/Transformation_(genetics) 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. https://en.wikipedia.org/wiki/Bacterial_conjugation https://en.wikipedia.org/wiki/Bacterial_conjugation Produce a literal pipe to transfer your antibiotic resistance super powers to your friend. Finally: https://en.wikipedia.org/wiki/Transduction_(genetics) https://en.wikipedia.org/wiki/Transduction_(genetics) 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.
  - chasil 3y ago
    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. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009535 https://journals.plos.org/plosgenetics/article?id=10.1371/jo...
    - matheusmoreira 3y ago
      So retroviruses literally integrated into our biological processes and became physiological? That's seriously awesome. https://en.wikipedia.org/wiki/Retrotransposon https://en.wikipedia.org/wiki/Retrotransposon > 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.
      - chasil 3y ago
        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." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802805/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802805/ https://www.science.org/content/article/origin-tasmanian-devil-tumors-identified https://www.science.org/content/article/origin-tasmanian-dev...
- robocat 3y ago
  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. [1] https://www.etymonline.com/word/sophisticated https://www.etymonline.com/word/sophisticated [2] fucked if I can find a good reference for my usage of “drop” here however hardly I tried [3] https://www.marketingsociety.com/the-library/counter-signalling-or-signalling-it’s-all-about-status https://www.marketingsociety.com/the-library/counter-signall... - I chose this link because it appears to be well written and uses “elucidate”[0], “dropped” and “aperçus”. [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.
  - woleium 3y ago
    idk man, elucidate is pretty common if you spend a lot of time reading scientific papers (I'm assuming oop does).
    - deleted 3y ago
      [deleted]
    - staunton 3y ago
      Which only proves the point robocat was making
    - robocat 3y ago
      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. However, failure is rife. [1] one Google result, different usage. [2] Sprachartisten
- Dalewyn 3y ago
  >confirm your cable is USB 4+ PD. I'm a tech nerd and wouldn't know WTF that means because USB is universally meaningless. Setting DIP switches is perfectly obvious, though. I miss the days messing with them and also jumpers.
chasil 3y ago
Is this ecDNA of similar size to the circular DNA of the mitochondria? This seems like a reversion of the form of DNA to a prokaryotic state.
- anonymouskimmer 3y ago
  It ranges from much smaller to much larger than mitochondrial genomes. https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA > 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. https://en.wikipedia.org/wiki/Linear_chromosome https://en.wikipedia.org/wiki/Linear_chromosome > Linear chromosomes are not limited to eukaryotic organisms; some prokaryotic organisms have linear chromosomes as well. > a good number of eukaryotic species do harbor linear mtDNA <mitochondrial DNA>, some even broken into multiple molecules
- robwwilliams 3y ago
  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. Wikipedia article: https://en.wikipedia.org/wiki/Extrachromosomal_DNA https://en.wikipedia.org/wiki/Extrachromosomal_DNA https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334176/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334176/
anonymouskimmer 3y ago
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.
robwwilliams 3y ago
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.
mbreese 3y ago
But they can also be devious. 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.

jtbayly 3y ago

Reading this gives me an understanding for how some of my friends feel when I talk about technology. “Make sure to set the dip switches on your SCSI drive and confirm your cable is USB 4+ PD.” Lol

matheusmoreira 3y ago
English Wikipedia is a surprisingly good resource. https://en.wikipedia.org/wiki/SiDNA https://en.wikipedia.org/wiki/SiDNA 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. https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA 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? Bacteria already have this capability - and more. https://en.wikipedia.org/wiki/Transformation_(genetics) https://en.wikipedia.org/wiki/Transformation_(genetics) 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. https://en.wikipedia.org/wiki/Bacterial_conjugation https://en.wikipedia.org/wiki/Bacterial_conjugation Produce a literal pipe to transfer your antibiotic resistance super powers to your friend. Finally: https://en.wikipedia.org/wiki/Transduction_(genetics) https://en.wikipedia.org/wiki/Transduction_(genetics) 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.
- chasil 3y ago
  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. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009535 https://journals.plos.org/plosgenetics/article?id=10.1371/jo...
  - matheusmoreira 3y ago
    So retroviruses literally integrated into our biological processes and became physiological? That's seriously awesome. https://en.wikipedia.org/wiki/Retrotransposon https://en.wikipedia.org/wiki/Retrotransposon > 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.
    - chasil 3y ago
      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." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802805/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802805/ https://www.science.org/content/article/origin-tasmanian-devil-tumors-identified https://www.science.org/content/article/origin-tasmanian-dev...
robocat 3y ago
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. [1] https://www.etymonline.com/word/sophisticated https://www.etymonline.com/word/sophisticated [2] fucked if I can find a good reference for my usage of “drop” here however hardly I tried [3] https://www.marketingsociety.com/the-library/counter-signalling-or-signalling-it’s-all-about-status https://www.marketingsociety.com/the-library/counter-signall... - I chose this link because it appears to be well written and uses “elucidate”[0], “dropped” and “aperçus”. [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.
- woleium 3y ago
  idk man, elucidate is pretty common if you spend a lot of time reading scientific papers (I'm assuming oop does).
  - deleted 3y ago
    [deleted]
  - staunton 3y ago
    Which only proves the point robocat was making
  - robocat 3y ago
    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. However, failure is rife. [1] one Google result, different usage. [2] Sprachartisten
Dalewyn 3y ago
>confirm your cable is USB 4+ PD. I'm a tech nerd and wouldn't know WTF that means because USB is universally meaningless. Setting DIP switches is perfectly obvious, though. I miss the days messing with them and also jumpers.

chasil 3y ago

Is this ecDNA of similar size to the circular DNA of the mitochondria? This seems like a reversion of the form of DNA to a prokaryotic state.

anonymouskimmer 3y ago
It ranges from much smaller to much larger than mitochondrial genomes. https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA https://en.wikipedia.org/wiki/Extrachromosomal_circular_DNA > 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. https://en.wikipedia.org/wiki/Linear_chromosome https://en.wikipedia.org/wiki/Linear_chromosome > Linear chromosomes are not limited to eukaryotic organisms; some prokaryotic organisms have linear chromosomes as well. > a good number of eukaryotic species do harbor linear mtDNA <mitochondrial DNA>, some even broken into multiple molecules
robwwilliams 3y ago
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. Wikipedia article: https://en.wikipedia.org/wiki/Extrachromosomal_DNA https://en.wikipedia.org/wiki/Extrachromosomal_DNA https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334176/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334176/

anonymouskimmer 3y ago

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.

robwwilliams 3y ago

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.

mbreese 3y ago

But they can also be devious. 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.