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.
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?
> In another parallel with the immune system, cadherin-related neuronal receptors (CNRs) are diversified synaptic proteins. The CNR genes belong to protocadherin (Pcdh) gene clusters. Genomic organizations of CNR/Pcdh genes are similar to that of the Ig and TCR genes. Somatic mutations in and combinatorial gene regulation of CNR/Pcdh transcripts during neurogenesis have been reported.
So as with evolution, more-or-less random variation generates diversity in the developing nervous system. And then there's selection.
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.
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.
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.
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.
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.
Basically, each node in a neural nets is unique akin to each neuron.
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, it's an interesting line of study, but let's not jump to conclusions.
: "[...] 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
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.
I'm saying that people should keep using the scientific method to formalize and test their hypotheses, but that esoteric traditions offer some interesting and under-explored paradigms within which to hypothesize. I'm being deliberately vague here because I don't want to bias you.
Note that this doesn't (nor should it) prevent actual, hypothesis-driven scientific inquiry. It just means the original idea came from elsewhere. If you look back at the history of scientific discovery, this happens quite often.
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!
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).
Surprisingly to most, this is not a mainstream opinion:
I would guess the main reason is that it leads to major problems with the current model of cancer.
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).
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.
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...
About the second paragraph: well, it was not really thought that differences are always detrimental to health, and there is quite a number of variant prioritization tools out there that try to find those variants that are causal compared to all the silent/no-effect mutations (mostly for comparing humans but also somatic).
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?
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?
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.
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.
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.
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.
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.
Unfortunately, looks like you have to register ("free"?) and sign-in to download the full text.
Other papers linked in article:
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.
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.
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.
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?
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.
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.
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".
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.
This is a trivial argument. The benefits of vaccination is both individual and that a large population of immunised individuals The idea of herd-immunity is a large percentage of the population is immunised the chances of disease spreading is minimised. 
Vaccinations are effective because individuals taking vaccinations develop immunity and if they come into contact with antigens again, anti-bodies are produced to fight. This is important for infants, who if exposed to an antigen, the time taken and effectiveness of response is weak. 
Hope you didn't miss my point though. Say you discover data that leads you to suggest a different vaccination procedure. That is difficult to communicate in an ideologically entrenched environment, don't you think?
Look how the parent post expressed discomfort already in the face of harmless new information relating to neurons.
There are plenty of examples of how accepted treatment is hard to shake. Take for example ^stomach ulcers^. Barry Marshall conducted self experiments to prove the H. pylori theory. The initial work started in '82. Marshall/Warren won the Nobel prize in 2005  for this work. It changed the way stomach ulcers were understood and the treatment.
I don't believe you, please show me some peer reviewed science instead of waiving around some ^hokey-pokey^ rubbery belief.
It seems you were making the argument that even if autism was linked to vaccines, the benefit would outweigh the cost. Now you are attacking me on a different point (that I didn't make)
Interesting article on role of social media. Obviously you are a hard core, a non-fence sitter, so I'll ignore you.
Vaccines are also a classic flamewar topic that, unless there's something genuinely new to be said, are off-topic here: https://news.ycombinator.com/newsguidelines.html.
Yes you're write Dang. Incivility vs factual evidence. Maybe I should be more tactful.
Facts not superstition, reducibility through empiricism. Rational thought instead emotion. Ideas like this were fought and won during ^the Enlightenment^ some 200 to 250 years ago. 
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 :)
Here's a thought experiment. The government has assisted in pushing the idea of "eggs are bad for you" for decades. In effect, many people truly believe that "eggs are bad for you" is a fact. If you, being slightly more knowledgable in the subject, tell one of those people that this is a load of bollox, and have a paper to back it up... would you actually convince them? You'd be one voice against many; a rebel against history. If you did managed to convince them, would it be due to raw truth, or due to the effectiveness of your rhetoric?
Though most things are at least a little subjective, there is always lets say a confidence value or percentage everyone could apply to some bit of knowledge, and while those may vary significantly across the population, some things could just objectively be said to be more likely than another. I dont think much of anything is 100% true, but 99%? Sure.
Im like, 99.99999% sure that this laptop is real and is about to run out of power, but I could be wrong.
The "truths" I was referring to are things we can't verify ourselves (due to practicality or lack of knowledge), yet are commonly believed or taken for granted. Some examples:
- World maps
- Authorship (of music, books, etc.)
- Photos (see #bowwowchallenge for a good laugh)
- The immutability of physics :)
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.
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".
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.
The far from perfect, and often illogical and uncritical realization of logic and critical thought.
... 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.
Actually, in most cases it isn't the scientists themselves, it is the PR department, or the journalists that are simply looking for a story
You obviously don't, as you would then know that I am very comfortable with approximations and continuums of belief. 'All of a person's cells share the same DNA' is far more true than its negation 'all of a person's cells do not share the same DNA'.
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.
Parent ask for those things to merely be tested. Not to have absolutely certain conclusions from those tests.
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.
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.
And instead they go with anecdotal shit like "holy water", "homeopathy", "christian 'science'", etc. which are even more untested.
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.
There was a brief mention of it at the bottom of the article.
Very large numbers do not.
> If they don't they are morons.
Perhaps, but that doesn't mean they don't exist.