7 ms·

Coming from a bioinformatics background this is really, really surprising to me. I knew there was always a chance of individual cells diverging from the shared

Coming from a bioinformatics background this is really, really surprising to me. I knew there was always a chance of individual cells diverging from the shared genome but we always considered that a hallmark of cancerous, abnormal growth. Thinking that you could have a trillion unique variations of the genome significantly ups the computational complexity of simulating an organism by a frightful order of magnitude. We are so much further from understanding biological systems than we ever thought. That's been the main lesson from the modern era of sequencing, genomics, and bioinformatics - we haven't learned nearly as much as we have unlearned.

pishpash 9y ago
Not sure why this _should_ be surprising, seeing as how multicellular organisms began as cooperative colonies of individuals.
- jboggan 9y ago
  Maybe? It's certainly the dominant theory but I wouldn't ascribe real truth to it. There are certainly species today that operate this way but there's no way to prove they represent the origin of multicellularity. There's no reason to even believe it happened only once.
- glubGlub 9y ago
  multicellular organisms began as cooperative colonies of *CLONES*. ftfy
lend000 9y ago
It's a pretty fascinating result, and it almost seems obvious in hindsight -- a statistical result of entropy which has profound implications for anti-aging research. The biggest takeaway for me is that physically isolated genetic diseases and asymmetries which manifest during an organism's growth may not be contained whatsoever in the organism's zygotes / passed along to its offspring (not that this was an impossible result before, but I suspect there is a higher probability of genetic independence than previously thought.) I would love to see comparisons of the standard deviations of "healthful" individuals to less healthy individuals. I would imagine that some genomes are far better at protecting themselves than others.
stefantalpalaru 9y ago
> you could have a trillion unique variations of the genome It's not really as bad as it sounds. The vast majority of those small mutations must be in the non-coding and non-regulating zone, with no effects on the genome's functionality. As the article mentions[1], it's an interesting line of study, but let's not jump to conclusions. [1]: "[...] each neuron may harbor hundreds of somatic mutations. Given the long life span of neurons and their central role in neural circuits and behavior, somatic mosaicism represents a potential mechanism that may contribute to neuronal diversity and the etiology of numerous neuropsychiatric disorders." - http://science.sciencemag.org/content/356/6336/eaal1641 http://science.sciencemag.org/content/356/6336/eaal1641
- jboggan 9y ago
  One major trend over the past 20 years has also been the realization that "non-coding" regions tend to be anything but, their effects are subtle and still being discovered.
  - patall 9y ago
    Nevertheless, it is long being observed that for example in cancer most mutations are passenger mutations. And this is true even more if they come from non-coding regions. Honestly, I am a bit surprised that you claim to have a bioinformatics background and are surprised about somatic variants. I mean, they are observed everywhere in NGS (and used on a daily basis for tracking pluripotent stem cell clonality and other things), there is not much surprising about it anymore.
    - jboggan 9y ago
      My unfinished PhD dissertation was about the topological differences in metabolic pathways expressed by various cancer cell lines in contrast to healthy tissue as a means of targeting metabolic "choke points" for future drugs - I'm not surprised about the existence of somatic variants but I am looking back and realizing how many of us were taking the uniformity of our systems for granted. Even when modeling the differences in a rapidly mutating cancer we always treated the variants as collections of discrete mutations that were uniform across the cluster. Then again this was ten years ago and you couldn't even think of sequencing enough lines to get at a cellular resolution. This really makes me want to pick that back up.
sjg007 9y ago
The more we learn, the less we know.
- dwaltrip 9y ago
  More like, the more we realize how little we actually knew before.
- TheOtherHobbes 9y ago
  The more we learn, the more our DNA knows.
anigbrowl 9y ago
Mystics have been talking about this sort of thing for ages. Perhaps you should look into some of those assertions to develop future investigative paradigms.
- wyager 9y ago
  One of the fundamental techniques used by most varieties of mysticism is to make proclamations vague enough that they can be plausibly associated with any fact that is discovered later on. This is how mystics trick gullible people into believing that they have hidden knowledge. The trick is that these proclamations can't be used to make useful predictions; they only fit the data in hindsight.
  - anigbrowl 9y ago
    You might want to look past the Deepak chopra types into the older mystery schools that don't solicit people's attention.
    - cariaso 9y ago
      Such as?
      - vedant 9y ago
        Theravada Buddhism.
      - anigbrowl 9y ago
        Hermeticism and derivatives of Egyptian mystery schools make for some interesting reading, and can be approached through academic avenues of archaeological/anthropological studies rather than woo-woo books and blogs. I'm definitely not suggesting it as an alternative to using scientific methods.
        olavk 9y ago
        I find hermeticim fascinating, but I don't really see the connection. Where is hermeticism talking about genomes and neurons?
daveguy 9y ago
Agreed. That's like orders of magnitude orders of magnitude. Definitely surprising, although in one of those hindsight realizations -- c.elegans has a specific consistent function for each cell and each cell under normal development. If 300+ cells of a worm can be that well orchestrated, of course slightly more complex creatures could. Evolution is a series of slight successes. What if the cells of the brain have their own genome because each one of the billions of cells has a near specific specialized function. Could cellular function be that precise? Each micron of tissue the result of specific evolutionary pressures?
- lend000 9y ago
  > What if the cells of the brain have their own genome because each one of the billions of cells has a near specific specialized function. That's the opposite of my interpretation -- it goes to show that even in the face of inevitable statistical noise, biological systems are incredibly fault-tolerant and durable. And furthermore, a neuron is just a neuron. It's unlikely that the genomic differences in a genius's neurons are significant compared to the overall genetic average which gave rise to a certain structure, certain proteins being more common, etc.
- devrandomguy 9y ago
  An interesting hypothesis, but difficult to reconcile with the surprisingly successful history of hemispherectomy [1]. Unless, perhaps, many unique neurons still serve nearly identical functions, despite their differences? Perhaps their uniqueness is a defense against disease, rather than functional specialization? I don't mean "functions" in the sense of classic neuroscience, like specialized regions of the brain; I am using it as a very generic term, for lack of a better one. [1] https://en.wikipedia.org/wiki/Hemispherectomy https://en.wikipedia.org/wiki/Hemispherectomy
- kleer001 9y ago
  > Could cellular function be that precise? Each micron of tissue the result of specific evolutionary pressures? If that's what the data says. It's probably an emergent quality from a set of simple rules being iterated. You can do a lot with a very very little if you're procedural about it. z_(n+1)=z_n^2+C
mirimir 9y ago
I suspect that we'll find this wherever there's a process involving massive generation of somatic diversity, plus functional selection. The immune system. The nervous system. Where else might that be useful?
woutercx 9y ago
My own hypothesis is that maybe our memories are stored in DNA in our brain cells. This article made my hypothesis a little more likely... Also, read the article "Microsoft experiments with DNA storage: 1,000,000,000 TB in a gram" at Ars Technica. https://arstechnica.com/information-technology/2016/04/microsoft-experiments-with-dna-storage-1000000000-tb-in-a-gram/ https://arstechnica.com/information-technology/2016/04/micro...
- FeepingCreature 9y ago
  Does your memory seem like it's big enough to require that much storage...? Mine doesn't.
- PeterisP 9y ago
  You hypothesis physically implausible - for starters, the speed at which memories are made and recalled is much, much faster than the timescale in which "writing" and "reading" of DNA happens. While you can encode a lot of data in arbitrary arrangements of a molecule (just as you can encode a lot of data in e.g. arbitrary arrangements of magnetic polarity in a dense material) if you have the right tools to do that, our cells have different tools specialized to do different processing on DNA molecules. There's no evidence to suppose that these changes in DNA are somehow controllable by external factors as opposed to random variations, and there's no evidence to suppose that these changes in DNA are readable in any other way than the usual creation of proteins required for functioning of the cell.
rdmirza 9y ago
This doesn't necessarily change anything about computing neural nets. You need to view the genomic variation as representing the complexity of each neural unit: its connections (in and out), it's propensity to fire, and function it operates by. The genome is just the code representing this information. Basically, each node in a neural nets is unique akin to each neuron.

pishpash 9y ago

Not sure why this _should_ be surprising, seeing as how multicellular organisms began as cooperative colonies of individuals.

jboggan 9y ago
Maybe? It's certainly the dominant theory but I wouldn't ascribe real truth to it. There are certainly species today that operate this way but there's no way to prove they represent the origin of multicellularity. There's no reason to even believe it happened only once.
glubGlub 9y ago
multicellular organisms began as cooperative colonies of *CLONES*. ftfy

lend000 9y ago

It's a pretty fascinating result, and it almost seems obvious in hindsight -- a statistical result of entropy which has profound implications for anti-aging research. The biggest takeaway for me is that physically isolated genetic diseases and asymmetries which manifest during an organism's growth may not be contained whatsoever in the organism's zygotes / passed along to its offspring (not that this was an impossible result before, but I suspect there is a higher probability of genetic independence than previously thought.) I would love to see comparisons of the standard deviations of "healthful" individuals to less healthy individuals. I would imagine that some genomes are far better at protecting themselves than others.

stefantalpalaru 9y ago

> you could have a trillion unique variations of the genome It's not really as bad as it sounds. The vast majority of those small mutations must be in the non-coding and non-regulating zone, with no effects on the genome's functionality. As the article mentions[1], it's an interesting line of study, but let's not jump to conclusions. [1]: "[...] each neuron may harbor hundreds of somatic mutations. Given the long life span of neurons and their central role in neural circuits and behavior, somatic mosaicism represents a potential mechanism that may contribute to neuronal diversity and the etiology of numerous neuropsychiatric disorders." - http://science.sciencemag.org/content/356/6336/eaal1641 http://science.sciencemag.org/content/356/6336/eaal1641

jboggan 9y ago
One major trend over the past 20 years has also been the realization that "non-coding" regions tend to be anything but, their effects are subtle and still being discovered.
- patall 9y ago
  Nevertheless, it is long being observed that for example in cancer most mutations are passenger mutations. And this is true even more if they come from non-coding regions. Honestly, I am a bit surprised that you claim to have a bioinformatics background and are surprised about somatic variants. I mean, they are observed everywhere in NGS (and used on a daily basis for tracking pluripotent stem cell clonality and other things), there is not much surprising about it anymore.
  - jboggan 9y ago
    My unfinished PhD dissertation was about the topological differences in metabolic pathways expressed by various cancer cell lines in contrast to healthy tissue as a means of targeting metabolic "choke points" for future drugs - I'm not surprised about the existence of somatic variants but I am looking back and realizing how many of us were taking the uniformity of our systems for granted. Even when modeling the differences in a rapidly mutating cancer we always treated the variants as collections of discrete mutations that were uniform across the cluster. Then again this was ten years ago and you couldn't even think of sequencing enough lines to get at a cellular resolution. This really makes me want to pick that back up.

sjg007 9y ago

The more we learn, the less we know.

dwaltrip 9y ago
More like, the more we realize how little we actually knew before.
TheOtherHobbes 9y ago
The more we learn, the more our DNA knows.

anigbrowl 9y ago

Mystics have been talking about this sort of thing for ages. Perhaps you should look into some of those assertions to develop future investigative paradigms.

wyager 9y ago
One of the fundamental techniques used by most varieties of mysticism is to make proclamations vague enough that they can be plausibly associated with any fact that is discovered later on. This is how mystics trick gullible people into believing that they have hidden knowledge. The trick is that these proclamations can't be used to make useful predictions; they only fit the data in hindsight.
- anigbrowl 9y ago
  You might want to look past the Deepak chopra types into the older mystery schools that don't solicit people's attention.
  - cariaso 9y ago
    Such as?
    - vedant 9y ago
      Theravada Buddhism.
    - anigbrowl 9y ago
      Hermeticism and derivatives of Egyptian mystery schools make for some interesting reading, and can be approached through academic avenues of archaeological/anthropological studies rather than woo-woo books and blogs. I'm definitely not suggesting it as an alternative to using scientific methods.
      - olavk 9y ago
        I find hermeticim fascinating, but I don't really see the connection. Where is hermeticism talking about genomes and neurons?

daveguy 9y ago

Agreed. That's like orders of magnitude orders of magnitude. Definitely surprising, although in one of those hindsight realizations -- c.elegans has a specific consistent function for each cell and each cell under normal development. If 300+ cells of a worm can be that well orchestrated, of course slightly more complex creatures could. Evolution is a series of slight successes. What if the cells of the brain have their own genome because each one of the billions of cells has a near specific specialized function. Could cellular function be that precise? Each micron of tissue the result of specific evolutionary pressures?

lend000 9y ago
> What if the cells of the brain have their own genome because each one of the billions of cells has a near specific specialized function. That's the opposite of my interpretation -- it goes to show that even in the face of inevitable statistical noise, biological systems are incredibly fault-tolerant and durable. And furthermore, a neuron is just a neuron. It's unlikely that the genomic differences in a genius's neurons are significant compared to the overall genetic average which gave rise to a certain structure, certain proteins being more common, etc.
devrandomguy 9y ago
An interesting hypothesis, but difficult to reconcile with the surprisingly successful history of hemispherectomy [1]. Unless, perhaps, many unique neurons still serve nearly identical functions, despite their differences? Perhaps their uniqueness is a defense against disease, rather than functional specialization? I don't mean "functions" in the sense of classic neuroscience, like specialized regions of the brain; I am using it as a very generic term, for lack of a better one. [1] https://en.wikipedia.org/wiki/Hemispherectomy https://en.wikipedia.org/wiki/Hemispherectomy
kleer001 9y ago
> Could cellular function be that precise? Each micron of tissue the result of specific evolutionary pressures? If that's what the data says. It's probably an emergent quality from a set of simple rules being iterated. You can do a lot with a very very little if you're procedural about it. z_(n+1)=z_n^2+C

mirimir 9y ago

I suspect that we'll find this wherever there's a process involving massive generation of somatic diversity, plus functional selection. The immune system. The nervous system. Where else might that be useful?

woutercx 9y ago

My own hypothesis is that maybe our memories are stored in DNA in our brain cells. This article made my hypothesis a little more likely... Also, read the article "Microsoft experiments with DNA storage: 1,000,000,000 TB in a gram" at Ars Technica. https://arstechnica.com/information-technology/2016/04/microsoft-experiments-with-dna-storage-1000000000-tb-in-a-gram/ https://arstechnica.com/information-technology/2016/04/micro...

FeepingCreature 9y ago
Does your memory seem like it's big enough to require that much storage...? Mine doesn't.
PeterisP 9y ago
You hypothesis physically implausible - for starters, the speed at which memories are made and recalled is much, much faster than the timescale in which "writing" and "reading" of DNA happens. While you can encode a lot of data in arbitrary arrangements of a molecule (just as you can encode a lot of data in e.g. arbitrary arrangements of magnetic polarity in a dense material) if you have the right tools to do that, our cells have different tools specialized to do different processing on DNA molecules. There's no evidence to suppose that these changes in DNA are somehow controllable by external factors as opposed to random variations, and there's no evidence to suppose that these changes in DNA are readable in any other way than the usual creation of proteins required for functioning of the cell.

rdmirza 9y ago

This doesn't necessarily change anything about computing neural nets. You need to view the genomic variation as representing the complexity of each neural unit: its connections (in and out), it's propensity to fire, and function it operates by. The genome is just the code representing this information. Basically, each node in a neural nets is unique akin to each neuron.