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.
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?
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.
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/micro...
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?
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.
> 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
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.
No two cells are ever genetically identical. Within a common hyper-mutable region, tandem repeats, the mutation rate is 10^-3 to 10^-5. There are over 10^5 tandem repeats in the genome, and therefore at least one mutation is expected for every cell division. Many other types of hyper-mutable regions exist in the human genome.
In this research they only examine one form of genetic variation, SNPs. These findings only reflect a small proportion of the somatic variation present in the body.
There is no real surprise in these results, but the data may nevertheless be useful!
(while most here understands CPU RAM RAII DRY etc., you might want to mentions that SNP means "single nucleotide polymorphism", which are mutations where just a single base pair differs.)
"A primary cause of somatic mutations has to do with errors during the DNA replication that occurs when cells divide—neural progenitor cells undergo tens of billions of cell divisions during brain development, proliferating rapidly to produce the 80 billion neurons in a mature brain."
Certainly there must be tens of billions of cell divisions to create all the neurons, but each neural progenitor cell would only divide 30-40 times, right?
I'm not surprised that there are mutations, but the number of mutations is remarkable to me, and seems like yet another evolutionary check on brain size that I hadn't considered (energy use, difficulty of birth, and difficulty of childhood being the more obvious ones).
>"Certainly there must be tens of billions of cell divisions to create all the neurons, but each neural progenitor cell would only divide 30-40 times, right?"
Well, DNA is kind of Big Data. And everyone who worked with Big Data knows that there will always be all kinds of inconsistencies and errors.
Personally, I was always skeptical that all non-sex human cells share the same DNA, it's just statistically unbelievable that billions of cells each having billions of DNA pairs would have then equal. I expected something like 1% of cells to have mutations.
Now they say that it's 100% for neurons. Exact 100% number is also pretty sketchy from statistical standpoint.
Nobody ever said that all cells share 100% of DNA in the sense you're implying. It's obvious that DNA undergoes dynamic processes, some of which will result in lasting differences. The accumulation of errors is the basic mechanism for cancer, which has been recognised for decades.
But it was previously thought that such differences were detrimental to function (and health). There were some mechanisms for modifying cells' DNA, collectively known as "epigenetics", but these were reversible, at least in principle.
This adds another dimension of complexity, which biology already had plenty of. My favourite is the double- or triple-coding DNA: because DNA is read in triplets, there are three possible reading frames. Some organisms have evolved DNA that produces entirely different, but independently useful proteins on two or even all three reading frames of the same DNA. Talk about efficiency...
Look at it from the other end - if there are on average a 1000 difference between two neurons, and a difference can be encapsulated by a single bit you'd have 2^1000 variants - you'd expect to have to look at 2^500 neurons to find a duplicate. And a difference is probably more than one bit.
Now they say that it's 100% for neurons. Exact 100% number is also pretty sketchy from statistical standpoint.
What class of problem is searching for duplicates or uniqueness among a set of billions of items? If it is a tractable problem, what is the most effective algorithm?
Sometimes I wonder how so much complexity and co-dependency has evolved on earth in such little time. Most estimates I've read say that we're likely within an order of magnitude of 100 trillion generations deep from the universal common ancestor at this point. That sounds like a lot, but not really. If you took 30 four sided die, you'd have to roll them a million trillion times to have a good shot at getting any specific permutation.
How many 'die rolls' does it take to get a selective feature to emerge in an organism? If you do a google image search for 'camouflage bugs', you'll find some brain-bending examples. There's clearly a selective advantage for some of those 'configurations', but how many generations would it take for each genetic mutation required to make a lichen katydid or an orchid mantis to converge?
Wait, the headline says no two alike, while the body text seems to go no further than that every cell is potentially different. What is it? If the somatic mutation rate is >1/neuron, that's a real surprise to me, but if it's "there's plenty of mosaicism and it makes a real difference", then not.
the more closely you look, the more obvious it becomes that this is the rule rather than the exception. I would be somewhat surprised if children have functional mutations rampant between neurons, and I suspect that some fraction of this is artifactual. But I have no doubt (does anyone?) that some degree of somatic mosaicism is the rule. About the only cells that tend to hang around much longer than neurons are blood stem cells, and as soon as you look closely at those, it's all but unavoidable.
Isn't this old news? The reason is vaguely similar to the DNA modification that happens in the immune system: recognition of self. In this case, the goal is to avoid loopback connections. Nerve cells that touch themselves are bad. By DNA modification, the cells get different surface protein and are thus able to avoid connecting to themselves.
Neurons practically never die, so the DNA itself will not directly reflect what a decades old braincell stores, though some mutations might influence how or if at all a certain neuron stores something. But since these mutations are random they are closer to defects (the article draws a connection to psychiatric diseases) than features.
But DNA can also be methylated, which is something that also happens in neurons and might be involved with actual memory.
And if you ever want to digitize a brain, then you might have to grab the DNA of 100 billion neurons as well, and there straightforward mutations are easier than just a somewhat transient methyl group here and there.
I read a research paper a couple years ago making an argument that neurons were using DNA as a kind of Turing tape for information storage. Very interesting but I can't seem to find it now.
Every single microprocessor in every computer is unique in its own way (small errors in production). It doesn't mean we can't compute with them, nor that the variation is useful or relevant.
> It doesn't mean we can't compute with them, nor that the variation is useful or relevant.
This is pretty much my understanding of it as well.
We can expect that, even though we're now at the point of being able to appreciate the minute differences in sequence from cell to cell, almost all changes will have no significant effect on phenotype. However, in aggregate, on the scale of tissues, the could be some interesting effects? But I doubt it.
No meaningful parts (which encodes proteins and gene regulation) are different, however. Nature does not work that way.
Comparison of two genomes as two billions-bases-long strings is meaningless and yields nonsense due to waste and introns. Genome isn't a uniform string in the first place.
Nothing to see here, except hipster's self-praise and want for attention.
I was told in science classes that all of a person's cells shared the same DNA. Now I learn, nobody ever actually tested to see if that was true. This is why people don't trust you, science.
Last week when I was picking up my kids from school, I challenged another parent to confirm her bumper sticker's claim that the Earth is flat. Sure enough, she told me to my face that yes, the Earth is flat, that I've "been lied to," and that I should "look into it." I'm still reeling from that.
I happen to know that "religion" is at play in this case, not the critical analysis of conflicting information. Likewise, my uncle, who is a lifelong engineer on the space program (via contractors), still believes very zealously in all sorts of superstition. There's apparently a cottage industry of authors who try to reconcile biblical literalism with contemporary science. Alan Kay talks about this somewhere, how even scientists are prone to ridiculous and unsupportable beliefs.
Right now (and maybe forever?) we have a Zeitgeist where "skepticism" appears to be tied to popular tribal identities, including evangelical Christianity. Despite the above, though, I doubt that anti-science sentiments are actually very widespread. I think we're hearing a lot about it because industries (energy in particular) are using people's distrust of authority and institutions to muddy the waters, so to speak, in public narratives where they see the truth as a threat.
> I was told in science classes that all of a person's cells shared the same DNA. Now I learn, nobody ever actually tested to see if that was true.
Actually, we've known that was wrong for a very long time, but also a useful approximation of the truth. Which is why very low level science classes tend to include it.
It's kind of like Newtonian mechanics, which you were probably also taught in science classes, and is also not true.
Science has become a pawn in the cultural conflict that seems to go on in America these days; the classic battlefield of "evolution vs. creation" has expanded to a World War 1 - style trench warfare going through all parts of society, with various major battles around things like "vaccination vs. autism" flaring up all the time.
This will doubtless hurt science. While a neutral science can trivially correct old theories when new evidence shows up, ideologically entrenched science can't easily give up ground. Saying two neurons don't share DNA might be harmless as it touches no sensitive spot in society - who cares? But what if multiple vaccinations (i.e. significant stress for the body to fight a disease) for for young kids actually turned out to be problematic in some circumstances? This won't be pretty on social media.
People don't trust "science" because people are not taught logic , critical thinking and the idea behind the scientific principle. Instead, people do celebrity worship (even of scientists !!!) and follow abrasive personalities.
When I teach biology classes, I emphasize that what I am teaching is an approximation of a much more complicated reality. Simplification is a useful didactic strategy. Students will get more details later if they need them (i.e., in graduate school or reading the original papers).
Unfair. Up until just a few years ago, genome sequencing cost thousands or hundreds of millions of dollars or was impossible. How was anyone going to check? The statement is almost entirely true (a few thousand changes out of 3 billion basepairs), anyway.
If we waited until we were absolutely sure of something we wouldn't be saying much ever would we? Isn't the whole point of science to postulate things and then prove or disprove them? Advances can also take "proven" things and prove them wrong.
You have gotten enough contra for this as this has nothing to do with science but teaching (and has long been tested), but one misconception I have not seen addressed yet is the fact that although there are some differences between cells, those are minimal from a genome stand point (a few changed letters of 10^9 in total). If you have two books with the same text and one has ten commas more, randomly distributed through the book, you would probably also call them identical(or not even notice) although they are not.
As a further note, while we can sequence the genome of cell bulks since about 2004, sequencing of single cell sequencing came up in the last ten years (with an accuracy of about 99.99%, so many random mistakes add up to a much higher degree of variation as is observed here), so if you did not went to science class less than ten years ago (with a teacher trained in the same time frame), your argument does not really make sense.
Thats not a reflection on science, its a reflection on how complicated the world really is..
We are taught progressively better approximations of the state of the art in school because its impossible to go from 0 to grasping everything in a flash. The state of the art itself changes as science tests old assumptions, which is also limited by the kinds of experiments they can run and tools - like CRISPR is enabling scientists access to precisely mutate genes and run experiments that were not possible before.
Its silly to blame science because all of genetics can't be explained as simply and neatly in 5 minutes as you'd like it to be.
The entire point of science is that trust is not needed, since you should be able to verify the experiments for yourself.
Also, please don't confuse the conclusion in some paper with the scientific method. Authors apply the scientific method to a subject and produce results (data). What they conclude from these results -- acquired through empirical study -- is entirely subjective (and often wrong). But that's how we learn.
i always wondered how differentiated cells can have completely identical DNA and still know which proteins to fold based on their specialized function. different types of cells even look very different!
What? People trust science. If they don't they are morons. Of course sometimes things and long held truths are proven wrong or different from new discoveries but that does not at all hurt science, this is the process.
[+] [-] jboggan|8 years ago|reply
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.
[+] [-] daveguy|8 years ago|reply
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|8 years ago|reply
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.
[+] [-] woutercx|8 years ago|reply
[+] [-] sjg007|8 years ago|reply
[+] [-] mirimir|8 years ago|reply
[+] [-] rdmirza|8 years ago|reply
Basically, each node in a neural nets is unique akin to each neuron.
[+] [-] stefantalpalaru|8 years ago|reply
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
[+] [-] pishpash|8 years ago|reply
[+] [-] anigbrowl|8 years ago|reply
[+] [-] Real_S|8 years ago|reply
In this research they only examine one form of genetic variation, SNPs. These findings only reflect a small proportion of the somatic variation present in the body.
There is no real surprise in these results, but the data may nevertheless be useful!
[+] [-] zeotroph|8 years ago|reply
[+] [-] reubenswartz|8 years ago|reply
Certainly there must be tens of billions of cell divisions to create all the neurons, but each neural progenitor cell would only divide 30-40 times, right?
I'm not surprised that there are mutations, but the number of mutations is remarkable to me, and seems like yet another evolutionary check on brain size that I hadn't considered (energy use, difficulty of birth, and difficulty of childhood being the more obvious ones).
[+] [-] nonbel|8 years ago|reply
Surprisingly to most, this is not a mainstream opinion: https://www.ncbi.nlm.nih.gov/pubmed/25459141
I would guess the main reason is that it leads to major problems with the current model of cancer.
[+] [-] deepsun|8 years ago|reply
Personally, I was always skeptical that all non-sex human cells share the same DNA, it's just statistically unbelievable that billions of cells each having billions of DNA pairs would have then equal. I expected something like 1% of cells to have mutations.
Now they say that it's 100% for neurons. Exact 100% number is also pretty sketchy from statistical standpoint.
[+] [-] matt4077|8 years ago|reply
But it was previously thought that such differences were detrimental to function (and health). There were some mechanisms for modifying cells' DNA, collectively known as "epigenetics", but these were reversible, at least in principle.
This adds another dimension of complexity, which biology already had plenty of. My favourite is the double- or triple-coding DNA: because DNA is read in triplets, there are three possible reading frames. Some organisms have evolved DNA that produces entirely different, but independently useful proteins on two or even all three reading frames of the same DNA. Talk about efficiency...
[+] [-] barrkel|8 years ago|reply
[+] [-] canoebuilder|8 years ago|reply
What class of problem is searching for duplicates or uniqueness among a set of billions of items? If it is a tractable problem, what is the most effective algorithm?
[+] [-] jcims|8 years ago|reply
How many 'die rolls' does it take to get a selective feature to emerge in an organism? If you do a google image search for 'camouflage bugs', you'll find some brain-bending examples. There's clearly a selective advantage for some of those 'configurations', but how many generations would it take for each genetic mutation required to make a lichen katydid or an orchid mantis to converge?
[+] [-] abecedarius|8 years ago|reply
[+] [-] dang|8 years ago|reply
[+] [-] apathy|8 years ago|reply
the more closely you look, the more obvious it becomes that this is the rule rather than the exception. I would be somewhat surprised if children have functional mutations rampant between neurons, and I suspect that some fraction of this is artifactual. But I have no doubt (does anyone?) that some degree of somatic mosaicism is the rule. About the only cells that tend to hang around much longer than neurons are blood stem cells, and as soon as you look closely at those, it's all but unavoidable.
[+] [-] tropo|8 years ago|reply
[+] [-] failrate|8 years ago|reply
[+] [-] zeotroph|8 years ago|reply
But DNA can also be methylated, which is something that also happens in neurons and might be involved with actual memory.
And if you ever want to digitize a brain, then you might have to grab the DNA of 100 billion neurons as well, and there straightforward mutations are easier than just a somewhat transient methyl group here and there.
[+] [-] akyu|8 years ago|reply
[+] [-] barrkel|8 years ago|reply
[+] [-] hammock|8 years ago|reply
[+] [-] RangerScience|8 years ago|reply
http://science.sciencemag.org/content/356/6336/eaal1641/tab-...
Unfortunately, looks like you have to register ("free"?) and sign-in to download the full text.
Other papers linked in article:
http://www.cell.com/neuron/fulltext/S0896-6273(16)00097-0
http://www.cell.com/neuron/fulltext/S0896-6273(12)00273-5
http://science.sciencemag.org/content/350/6256/94/tab-pdf
[+] [-] skosuri|8 years ago|reply
[+] [-] dvt|8 years ago|reply
[+] [-] sndean|8 years ago|reply
This is pretty much my understanding of it as well.
We can expect that, even though we're now at the point of being able to appreciate the minute differences in sequence from cell to cell, almost all changes will have no significant effect on phenotype. However, in aggregate, on the scale of tissues, the could be some interesting effects? But I doubt it.
[+] [-] lngnmn|8 years ago|reply
Comparison of two genomes as two billions-bases-long strings is meaningless and yields nonsense due to waste and introns. Genome isn't a uniform string in the first place.
Nothing to see here, except hipster's self-praise and want for attention.
[+] [-] unknown|8 years ago|reply
[deleted]
[+] [-] danjoc|8 years ago|reply
[+] [-] gavinpc|8 years ago|reply
Funny... but I wish that were the case.
Last week when I was picking up my kids from school, I challenged another parent to confirm her bumper sticker's claim that the Earth is flat. Sure enough, she told me to my face that yes, the Earth is flat, that I've "been lied to," and that I should "look into it." I'm still reeling from that.
I happen to know that "religion" is at play in this case, not the critical analysis of conflicting information. Likewise, my uncle, who is a lifelong engineer on the space program (via contractors), still believes very zealously in all sorts of superstition. There's apparently a cottage industry of authors who try to reconcile biblical literalism with contemporary science. Alan Kay talks about this somewhere, how even scientists are prone to ridiculous and unsupportable beliefs.
Right now (and maybe forever?) we have a Zeitgeist where "skepticism" appears to be tied to popular tribal identities, including evangelical Christianity. Despite the above, though, I doubt that anti-science sentiments are actually very widespread. I think we're hearing a lot about it because industries (energy in particular) are using people's distrust of authority and institutions to muddy the waters, so to speak, in public narratives where they see the truth as a threat.
[+] [-] dragonwriter|8 years ago|reply
Actually, we've known that was wrong for a very long time, but also a useful approximation of the truth. Which is why very low level science classes tend to include it.
It's kind of like Newtonian mechanics, which you were probably also taught in science classes, and is also not true.
[+] [-] UweSchmidt|8 years ago|reply
Science has become a pawn in the cultural conflict that seems to go on in America these days; the classic battlefield of "evolution vs. creation" has expanded to a World War 1 - style trench warfare going through all parts of society, with various major battles around things like "vaccination vs. autism" flaring up all the time.
This will doubtless hurt science. While a neutral science can trivially correct old theories when new evidence shows up, ideologically entrenched science can't easily give up ground. Saying two neurons don't share DNA might be harmless as it touches no sensitive spot in society - who cares? But what if multiple vaccinations (i.e. significant stress for the body to fight a disease) for for young kids actually turned out to be problematic in some circumstances? This won't be pretty on social media.
[+] [-] vowelless|8 years ago|reply
[+] [-] biomcgary|8 years ago|reply
[+] [-] gwern|8 years ago|reply
[+] [-] markcerqueira|8 years ago|reply
[+] [-] patall|8 years ago|reply
As a further note, while we can sequence the genome of cell bulks since about 2004, sequencing of single cell sequencing came up in the last ten years (with an accuracy of about 99.99%, so many random mistakes add up to a much higher degree of variation as is observed here), so if you did not went to science class less than ten years ago (with a teacher trained in the same time frame), your argument does not really make sense.
[+] [-] zaptheimpaler|8 years ago|reply
We are taught progressively better approximations of the state of the art in school because its impossible to go from 0 to grasping everything in a flash. The state of the art itself changes as science tests old assumptions, which is also limited by the kinds of experiments they can run and tools - like CRISPR is enabling scientists access to precisely mutate genes and run experiments that were not possible before.
Its silly to blame science because all of genetics can't be explained as simply and neatly in 5 minutes as you'd like it to be.
[+] [-] fao_|8 years ago|reply
And instead they go with anecdotal shit like "holy water", "homeopathy", "christian 'science'", etc. which are even more untested.
[+] [-] runeks|8 years ago|reply
Also, please don't confuse the conclusion in some paper with the scientific method. Authors apply the scientific method to a subject and produce results (data). What they conclude from these results -- acquired through empirical study -- is entirely subjective (and often wrong). But that's how we learn.
[+] [-] leeoniya|8 years ago|reply
[+] [-] unknown|8 years ago|reply
[deleted]
[+] [-] snackai|8 years ago|reply
[+] [-] unknown|8 years ago|reply
[deleted]