11 ms·

Every neuron potentially has a different genome than those it's connected to

177 points by molecule 9y ago

danjoc 9y ago
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.
- markcerqueira 9y ago
  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.
  - coldtea 9y ago
    >If we waited until we were absolutely sure of something we wouldn't be saying much ever would we? Parent ask for those things to merely be tested. Not to have absolutely certain conclusions from those tests.
  - pbhjpbhj 9y ago
    >we wouldn't be saying much ever would we? // We could say plenty within the standard scientific framework of presenting hypotheses, testing, promoting to theory. Indeed if you're a scientist that follows a falsificationist methodology for the progress of scientific understanding then all science - all knowledge, for realists - is within that framework. >Advances can also take "proven" things and prove them wrong. // No, because proven means something is true, if it's proven that the claim was wrong then it was not proven in the first place. In _science_ things are held as theories. If they're not yet falsified, they get stronger the more they're tested and not found lacking. The only "truths" are our assumptions/axioms, claims for scientific truth beyond that are scientism.
- leeoniya 9y ago
  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!
  - marcosdumay 9y ago
    Ok, but this article does not explain that.
  - charlieflowers 9y ago
    I'm no expert but I have heard this explained. You can explain it without needing cells to have different DNA. Differentiated cells express different genes from the same genome.
  - khedoros1 9y ago
    I think that a one-word answer would be "epigenetics". Sections of genes are turned on and off by various chemical processes, so that the genes that are actively transcribed into proteins can change without the underlying DNA changing. There was a brief mention of it at the bottom of the article.
  - roywiggins 9y ago
    Differentiation. https://en.wikipedia.org/wiki/Cellular_differentiation https://en.wikipedia.org/wiki/Cellular_differentiation
  - matt4077 9y ago
    Epigenetics, as has been pointed out. But also just the very basic mechanisms of hormones and other signalling and regulating molecules. DNA is just the code. Cells also keep 'state', mostly through the specific molecules in the cytosol.
- fao_ 9y ago
  > This is why people don't trust you, science. And instead they go with anecdotal shit like "holy water", "homeopathy", "christian 'science'", etc. which are even more untested.
  - dragonwriter 9y ago
    Or, in many cases, tested and conclusively demonstrated not to be real.
- biomcgary 9y ago
  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).
- snackai 9y ago
  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.
  - dragonwriter 9y ago
    > People trust science. Very large numbers do not. > If they don't they are morons. Perhaps, but that doesn't mean they don't exist.
- gavinpc 9y ago
  > This is why people don't trust you, science. 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.
  - UweSchmidt 9y ago
    As you said, superstitions didn't prevent your uncle from building rockets. I propose to 'allow' personal beliefs and tribal identities and keep science out of the line of fire as much as possible. It's unfortunate when religion influences real world politics, likewise it's unfortunate that atheist preachers use science as a platform and create an us-vs-them mentality. Also, quite a bit of that half-serious scepticism is actually critical thinking; an experiment in researching topics, finding additional angles to complex issues and expressing dissenting opinions which was not possible before the internet. So let's say the moon landing was fake, just for fun. Let's look at the fotos, look for clues or contradictions in old publications. Let's say you're ill and in pain, and none of the doctors could help or give relief. It's easy to see the appeal of finding your own truth, no?
  - ralfd 9y ago
    Sure that was not said in an ironic way? Flat earth stickers surely have to be satirical.
- vowelless 9y ago
  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.
  - coldtea 9y ago
    >People don't trust "science" because people are not taught logic, critical thinking and the idea behind the scientific principle. Well, science is not the idea of "logic, critical thinking and the scientific principle" -- it's its realization in practice. And from private interests to careerism and ego, that practice is quite far from the idea.
    - vowelless 9y ago
      I think we are saying the same thing. You say science is the realization of logic and critical thought. I'm saying "people" are uneducated about logic and critical thought and hence will clearly not understand "science".
      - beagle3 9y ago
        I don't think you are saying the same thing. You say "people don't trust science because their education is lacking". Other guy says "people don't trust science because science is often perverted to promote a specific agenda". Neither of you is wrong, but if I understand correctly you aren't saying the same thing.
      - coldtea 9y ago
        >You say science is the realization of logic and critical thought The far from perfect, and often illogical and uncritical realization of logic and critical thought.
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- dragonwriter 9y ago
  > 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.
  - nikofeyn 9y ago
    newtonian mechanics is perfectly true in certain contexts.
    - omginternets 9y ago
      >perfectly true Stricto-sensu it's not true. Newtonian mechanics constitute a model, and all models have error-terms. As the saying goes, "All models are wrong; some models are useful".
  - danjoc 9y ago
    >useful approximation of the truth This must be fantastic material for trolling... "What Clapper said in front of Congress was a useful approximation of the truth." You almost got me. Well played.
- UweSchmidt 9y ago
  That's not why people don't trust science. 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.
  - joshjje 9y ago
    What do people who dont trust science trust instead? Not the religious nuts who would prefer to pray away an illness than get treatment, but the rest, lol.
    - simplify 9y ago
      Follower of Christ here. The short answer is, you can't trust anything. Science is neutral and good because, if true, you can reproduce and see for yourself. The problem is, you can't trust the reporting. I see science-related reports the same way I see political reports – bias with an incentive to lie. If I were well-versed enough to read the white papers, I would probably trust it a little more. But even then you can't be certain unless you perform the experiment yourself; it's not uncommon for scientists to leave out inconvenient data to get the result they want. Such is the state of this world – you can't truly know a fact for a fact unless you actually see it for yourself. And even then there's room for doubt :)
      - joshjje 9y ago
        Thats certainly better than trusting just to faith to solve things and understandable. I would say about the same. Its an interesting philosophical problem, what we know, and how we know it. I guess instead of black and white trust or not trust I would rephrase and question peoples distrust of highly likely things.
- gwern 9y ago
  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.
  - pbhjpbhj 9y ago
    >How was anyone going to check? // ... that is why one shouldn't trust the current science establishment, writ large, IMO. If you ascribe to a falsificationist/Popperian scientific method as most claim to do in the scientific establishment then what you should have been claiming is that "our best theory, as yet unfalsified, is that all cells of the human body have the same DNA". It is in no way contingent on the ability of anyone to check, because scientific statements [within the aforementioned philosophical frameworks] can not be confirmed to be true. That's as strong as it gets, that's the most that "science" can say; but instead of keeping within the epistemological limits of scientific enquiry scientists want to go further [arguably they long for certainty with a sort of religious fervour], so they say things like "all human cells share the same DNA" and print it in text books, and repeat it year after year to school kids and anyone else listening. Then, when it turns out that it's wrong that is the point where people don't trust "science", and quite rightly so IMO. The story now is "science was wrong" whilst in fact it was the scientist who refused to keep to the limits of what science can offer with regards to certainty that were wrong. I think you can argue the pushing of facts to be blindly accepted(!) as a methodology for teaching of science, but I don't find that line of argument compelling; it's also something that most scientists will rail against when done outside of the scientific establishment. [Sorry, but still smarting from high-school chemistry "well actually all that stuff we told you about atoms being like solar-systems was a huge lie, s- p- d- and f- orbitals is where it's at", only then to be told 2 years later "oh, that was all a huge lie, electrons aren't confined in that way, they don't even orbit".] >The statement is almost entirely true // Lol, are you a politician, this is what's also known as "false". The statement that "all of a person's cells [share] the same DNA" (by danjoc) has been demonstrably false for years, _THAT_ is science. I'm surprised to see this sort of defence of anti-scientific thinking from you [you don't know me I just know your work]. The little bits where a statement that appeared a priori to be true yet isn't, they are the interesting bits, they're the bits where scientific curiosity is focussed, they're usually the important bits. "It's nearly right" is anathema to scientific progress.
- runeks 9y ago
  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.
- patall 9y ago
  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.
- zaptheimpaler 9y ago
  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.
failrate 9y ago
I wonder if this is involved in storing information in the brain.
- hammock 9y ago
  Thought the same. Or computation, or any other sort of functional benefit...
- barrkel 9y ago
  Initial randomization of neural network weights?
- zeotroph 9y ago
  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.
- akyu 9y ago
  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.
jboggan 9y ago
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.
deepsun 9y ago
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.
- barrkel 9y ago
  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.
- canoebuilder 9y ago
  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?
- matt4077 9y ago
  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...
Real_S 9y ago
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!
- zeotroph 9y ago
  (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.)
abecedarius 9y ago
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.
- dang 9y ago
  Good catch. We've changed the title above to a representative phrase from (I think) the paragraph you're referring to.
  - abecedarius 9y ago
    OTOH Real_S comments that the rate is indeed >1. So huh, I learned something.
reubenswartz 9y ago
"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).
- nonbel 9y ago
  >"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?" Surprisingly to most, this is not a mainstream opinion: https://www.ncbi.nlm.nih.gov/pubmed/25459141 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.
  - reubenswartz 9y ago
    Thanks for the link. Very interesting stuff. Also worth noting that there's a difference between mutation and cancer, although of course they're related. Just as mice and people get cancer at similar rates, so do elephants, which have many more cell divisions, but have more elaborate anticancer mechanisms (presumably because elephants lacking them died of cancer).
    - nonbel 9y ago
      If you give humans 2^53 divisions (as in that paper) and elephants have ~100x the mass of humans, as a rough estimate they would require 2^60 divisions. So about 7 more divisions per stem cell to live as long as the usual human (they usually don't live that long).
      - 9y ago
skosuri 9y ago
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.
- sndean 9y ago
  > 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.
- dvt 9y ago
  This is an incredibly reductive analogy. The whole point of the article is that the neuronal variation does seem to be relevant.
  - skosuri 9y ago
    It seems to exist. Not clear there is a lot of evidence it's relevant. If you sequence a tissue that has cancer or some other disease that causes increased cell division, you will see more somatic variation. Not sure why this is particularly surprising or interesting. It's been known for a while now. If somatic variation was important for brain development or function (like it is in the adaptive immune system), that indeed would be super surprising, but that's not what I'm seeing here.
    - mirimir 9y ago
      A key aspect of CNS development is massive overproduction of neurons, and then selection for useful ones. The idea that somatic variation plays a role there is not novel. https://scholar.google.com/scholar?q=development+somatic+variation+neuron https://scholar.google.com/scholar?q=development+somatic+var...
tropo 9y ago
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.
lngnmn 9y ago
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.
jcims 9y ago
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?
- simooooo 9y ago
  I don't think dice are a good comparison, as each roll is a new "state", knowing nothing about the previous. Vs. evolution which has kind of a feedback loop which influences future output.
- runeks 9y ago
  Why do you assume that progress only happens at the interface between generations? If that were the case, human beings would be at a huge disadvantage, given that we wait ~20 years or so before reproducing. The longer we wait before reproducing, the more intelligent the decision to reproduce will be -- which is what determines the genome of the resulting offspring.
- kahoon 9y ago
  > 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? If you pose the question like that with the posteriori knowledge in mind, then yes, these configurations are highly improbable. I think another question that could be asked is: How many generations would it take for some mutations to produce some camouflage effect in some of the millions of existing species? Surely some mutations that produce camouflage effects will happen.
apathy 9y ago
https://www.nature.com/articles/ncomms12484 https://www.nature.com/articles/ncomms12484 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.
- apathy 9y ago
  God damn it, that Science paper is piss weak even for a Science paper. It's yet another consortium advertisement. Meanwhile mapping of somatic mutations in blood progenitors has been happening for a decade.
  - patall 9y ago
    This exactly. Somatic variants are one of the most common things around. I always wonder why HN will almost never upvote a general informatics research article instead of a good review and with other fields of research it is the other way around where a review would be much better suited.
deleted 9y ago
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RangerScience 9y ago
Main paper: http://science.sciencemag.org/content/356/6336/eaal1641/tab-pdf 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(16)00097-0 http://www.cell.com/neuron/fulltext/S0896-6273(12)00273-5 http://www.cell.com/neuron/fulltext/S0896-6273(12)00273-5 http://science.sciencemag.org/content/350/6256/94/tab-pdf http://science.sciencemag.org/content/350/6256/94/tab-pdf

177 points by molecule 9y ago

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.

markcerqueira 9y ago
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.
- coldtea 9y ago
  >If we waited until we were absolutely sure of something we wouldn't be saying much ever would we? Parent ask for those things to merely be tested. Not to have absolutely certain conclusions from those tests.
- pbhjpbhj 9y ago
  >we wouldn't be saying much ever would we? // We could say plenty within the standard scientific framework of presenting hypotheses, testing, promoting to theory. Indeed if you're a scientist that follows a falsificationist methodology for the progress of scientific understanding then all science - all knowledge, for realists - is within that framework. >Advances can also take "proven" things and prove them wrong. // No, because proven means something is true, if it's proven that the claim was wrong then it was not proven in the first place. In _science_ things are held as theories. If they're not yet falsified, they get stronger the more they're tested and not found lacking. The only "truths" are our assumptions/axioms, claims for scientific truth beyond that are scientism.
leeoniya 9y ago
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!
- marcosdumay 9y ago
  Ok, but this article does not explain that.
- charlieflowers 9y ago
  I'm no expert but I have heard this explained. You can explain it without needing cells to have different DNA. Differentiated cells express different genes from the same genome.
- khedoros1 9y ago
  I think that a one-word answer would be "epigenetics". Sections of genes are turned on and off by various chemical processes, so that the genes that are actively transcribed into proteins can change without the underlying DNA changing. There was a brief mention of it at the bottom of the article.
- roywiggins 9y ago
  Differentiation. https://en.wikipedia.org/wiki/Cellular_differentiation https://en.wikipedia.org/wiki/Cellular_differentiation
- matt4077 9y ago
  Epigenetics, as has been pointed out. But also just the very basic mechanisms of hormones and other signalling and regulating molecules. DNA is just the code. Cells also keep 'state', mostly through the specific molecules in the cytosol.
fao_ 9y ago
> This is why people don't trust you, science. And instead they go with anecdotal shit like "holy water", "homeopathy", "christian 'science'", etc. which are even more untested.
- dragonwriter 9y ago
  Or, in many cases, tested and conclusively demonstrated not to be real.
biomcgary 9y ago
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).
snackai 9y ago
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.
- dragonwriter 9y ago
  > People trust science. Very large numbers do not. > If they don't they are morons. Perhaps, but that doesn't mean they don't exist.
gavinpc 9y ago
> This is why people don't trust you, science. 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.
- UweSchmidt 9y ago
  As you said, superstitions didn't prevent your uncle from building rockets. I propose to 'allow' personal beliefs and tribal identities and keep science out of the line of fire as much as possible. It's unfortunate when religion influences real world politics, likewise it's unfortunate that atheist preachers use science as a platform and create an us-vs-them mentality. Also, quite a bit of that half-serious scepticism is actually critical thinking; an experiment in researching topics, finding additional angles to complex issues and expressing dissenting opinions which was not possible before the internet. So let's say the moon landing was fake, just for fun. Let's look at the fotos, look for clues or contradictions in old publications. Let's say you're ill and in pain, and none of the doctors could help or give relief. It's easy to see the appeal of finding your own truth, no?
- ralfd 9y ago
  Sure that was not said in an ironic way? Flat earth stickers surely have to be satirical.
vowelless 9y ago
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.
- coldtea 9y ago
  >People don't trust "science" because people are not taught logic, critical thinking and the idea behind the scientific principle. Well, science is not the idea of "logic, critical thinking and the scientific principle" -- it's its realization in practice. And from private interests to careerism and ego, that practice is quite far from the idea.
  - vowelless 9y ago
    I think we are saying the same thing. You say science is the realization of logic and critical thought. I'm saying "people" are uneducated about logic and critical thought and hence will clearly not understand "science".
    - beagle3 9y ago
      I don't think you are saying the same thing. You say "people don't trust science because their education is lacking". Other guy says "people don't trust science because science is often perverted to promote a specific agenda". Neither of you is wrong, but if I understand correctly you aren't saying the same thing.
    - coldtea 9y ago
      >You say science is the realization of logic and critical thought The far from perfect, and often illogical and uncritical realization of logic and critical thought.
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dragonwriter 9y ago
> 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.
- nikofeyn 9y ago
  newtonian mechanics is perfectly true in certain contexts.
  - omginternets 9y ago
    >perfectly true Stricto-sensu it's not true. Newtonian mechanics constitute a model, and all models have error-terms. As the saying goes, "All models are wrong; some models are useful".
- danjoc 9y ago
  >useful approximation of the truth This must be fantastic material for trolling... "What Clapper said in front of Congress was a useful approximation of the truth." You almost got me. Well played.
UweSchmidt 9y ago
That's not why people don't trust science. 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.
- joshjje 9y ago
  What do people who dont trust science trust instead? Not the religious nuts who would prefer to pray away an illness than get treatment, but the rest, lol.
  - simplify 9y ago
    Follower of Christ here. The short answer is, you can't trust anything. Science is neutral and good because, if true, you can reproduce and see for yourself. The problem is, you can't trust the reporting. I see science-related reports the same way I see political reports – bias with an incentive to lie. If I were well-versed enough to read the white papers, I would probably trust it a little more. But even then you can't be certain unless you perform the experiment yourself; it's not uncommon for scientists to leave out inconvenient data to get the result they want. Such is the state of this world – you can't truly know a fact for a fact unless you actually see it for yourself. And even then there's room for doubt :)
    - joshjje 9y ago
      Thats certainly better than trusting just to faith to solve things and understandable. I would say about the same. Its an interesting philosophical problem, what we know, and how we know it. I guess instead of black and white trust or not trust I would rephrase and question peoples distrust of highly likely things.
gwern 9y ago
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.
- pbhjpbhj 9y ago
  >How was anyone going to check? // ... that is why one shouldn't trust the current science establishment, writ large, IMO. If you ascribe to a falsificationist/Popperian scientific method as most claim to do in the scientific establishment then what you should have been claiming is that "our best theory, as yet unfalsified, is that all cells of the human body have the same DNA". It is in no way contingent on the ability of anyone to check, because scientific statements [within the aforementioned philosophical frameworks] can not be confirmed to be true. That's as strong as it gets, that's the most that "science" can say; but instead of keeping within the epistemological limits of scientific enquiry scientists want to go further [arguably they long for certainty with a sort of religious fervour], so they say things like "all human cells share the same DNA" and print it in text books, and repeat it year after year to school kids and anyone else listening. Then, when it turns out that it's wrong that is the point where people don't trust "science", and quite rightly so IMO. The story now is "science was wrong" whilst in fact it was the scientist who refused to keep to the limits of what science can offer with regards to certainty that were wrong. I think you can argue the pushing of facts to be blindly accepted(!) as a methodology for teaching of science, but I don't find that line of argument compelling; it's also something that most scientists will rail against when done outside of the scientific establishment. [Sorry, but still smarting from high-school chemistry "well actually all that stuff we told you about atoms being like solar-systems was a huge lie, s- p- d- and f- orbitals is where it's at", only then to be told 2 years later "oh, that was all a huge lie, electrons aren't confined in that way, they don't even orbit".] >The statement is almost entirely true // Lol, are you a politician, this is what's also known as "false". The statement that "all of a person's cells [share] the same DNA" (by danjoc) has been demonstrably false for years, _THAT_ is science. I'm surprised to see this sort of defence of anti-scientific thinking from you [you don't know me I just know your work]. The little bits where a statement that appeared a priori to be true yet isn't, they are the interesting bits, they're the bits where scientific curiosity is focussed, they're usually the important bits. "It's nearly right" is anathema to scientific progress.
runeks 9y ago
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.
patall 9y ago
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.
zaptheimpaler 9y ago
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.

failrate 9y ago

I wonder if this is involved in storing information in the brain.

hammock 9y ago
Thought the same. Or computation, or any other sort of functional benefit...
barrkel 9y ago
Initial randomization of neural network weights?
zeotroph 9y ago
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.
akyu 9y ago
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.

jboggan 9y ago

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.

deepsun 9y ago

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.

barrkel 9y ago
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.
canoebuilder 9y ago
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?
matt4077 9y ago
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...

Real_S 9y ago

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!

zeotroph 9y ago
(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.)

abecedarius 9y ago

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.

dang 9y ago
Good catch. We've changed the title above to a representative phrase from (I think) the paragraph you're referring to.
- abecedarius 9y ago
  OTOH Real_S comments that the rate is indeed >1. So huh, I learned something.

reubenswartz 9y ago

"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).

nonbel 9y ago
>"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?" Surprisingly to most, this is not a mainstream opinion: https://www.ncbi.nlm.nih.gov/pubmed/25459141 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.
- reubenswartz 9y ago
  Thanks for the link. Very interesting stuff. Also worth noting that there's a difference between mutation and cancer, although of course they're related. Just as mice and people get cancer at similar rates, so do elephants, which have many more cell divisions, but have more elaborate anticancer mechanisms (presumably because elephants lacking them died of cancer).
  - nonbel 9y ago
    If you give humans 2^53 divisions (as in that paper) and elephants have ~100x the mass of humans, as a rough estimate they would require 2^60 divisions. So about 7 more divisions per stem cell to live as long as the usual human (they usually don't live that long).
    - 9y ago

skosuri 9y ago

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.

sndean 9y ago
> 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.
dvt 9y ago
This is an incredibly reductive analogy. The whole point of the article is that the neuronal variation does seem to be relevant.
- skosuri 9y ago
  It seems to exist. Not clear there is a lot of evidence it's relevant. If you sequence a tissue that has cancer or some other disease that causes increased cell division, you will see more somatic variation. Not sure why this is particularly surprising or interesting. It's been known for a while now. If somatic variation was important for brain development or function (like it is in the adaptive immune system), that indeed would be super surprising, but that's not what I'm seeing here.
  - mirimir 9y ago
    A key aspect of CNS development is massive overproduction of neurons, and then selection for useful ones. The idea that somatic variation plays a role there is not novel. https://scholar.google.com/scholar?q=development+somatic+variation+neuron https://scholar.google.com/scholar?q=development+somatic+var...

tropo 9y ago

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.

lngnmn 9y ago

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.

jcims 9y ago

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?

simooooo 9y ago
I don't think dice are a good comparison, as each roll is a new "state", knowing nothing about the previous. Vs. evolution which has kind of a feedback loop which influences future output.
runeks 9y ago
Why do you assume that progress only happens at the interface between generations? If that were the case, human beings would be at a huge disadvantage, given that we wait ~20 years or so before reproducing. The longer we wait before reproducing, the more intelligent the decision to reproduce will be -- which is what determines the genome of the resulting offspring.
kahoon 9y ago
> 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? If you pose the question like that with the posteriori knowledge in mind, then yes, these configurations are highly improbable. I think another question that could be asked is: How many generations would it take for some mutations to produce some camouflage effect in some of the millions of existing species? Surely some mutations that produce camouflage effects will happen.

apathy 9y ago

https://www.nature.com/articles/ncomms12484 https://www.nature.com/articles/ncomms12484 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.

apathy 9y ago
God damn it, that Science paper is piss weak even for a Science paper. It's yet another consortium advertisement. Meanwhile mapping of somatic mutations in blood progenitors has been happening for a decade.
- patall 9y ago
  This exactly. Somatic variants are one of the most common things around. I always wonder why HN will almost never upvote a general informatics research article instead of a good review and with other fields of research it is the other way around where a review would be much better suited.

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RangerScience 9y ago

Main paper: http://science.sciencemag.org/content/356/6336/eaal1641/tab-pdf 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(16)00097-0 http://www.cell.com/neuron/fulltext/S0896-6273(12)00273-5 http://www.cell.com/neuron/fulltext/S0896-6273(12)00273-5 http://science.sciencemag.org/content/350/6256/94/tab-pdf http://science.sciencemag.org/content/350/6256/94/tab-pdf