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

177 pointsby moleculeabout 8 years ago

13 comments

jbogganabout 8 years 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.<p>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.<p>That&#x27;s been the main lesson from the modern era of sequencing, genomics, and bioinformatics - we haven&#x27;t learned nearly as much as we have unlearned.
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Real_Sabout 8 years 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.<p>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.<p>There is no real surprise in these results, but the data may nevertheless be useful!
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reubenswartzabout 8 years ago
&quot;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.&quot;<p>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?<p>I&#x27;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&#x27;t considered (energy use, difficulty of birth, and difficulty of childhood being the more obvious ones).
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deepsunabout 8 years 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.<p>Personally, I was always skeptical that all non-sex human cells share the same DNA, it&#x27;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.<p>Now they say that it&#x27;s 100% for neurons. Exact 100% number is also pretty sketchy from statistical standpoint.
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jcimsabout 8 years ago
Sometimes I wonder how so much complexity and co-dependency has evolved on earth in such little time. Most estimates I&#x27;ve read say that we&#x27;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&#x27;d have to roll them a million trillion times to have a good shot at getting any specific permutation.<p>How many &#x27;die rolls&#x27; does it take to get a selective feature to emerge in an organism? If you do a google image search for &#x27;camouflage bugs&#x27;, you&#x27;ll find some brain-bending examples. There&#x27;s clearly a selective advantage for some of those &#x27;configurations&#x27;, but how many generations would it take for each genetic mutation required to make a lichen katydid or an orchid mantis to converge?
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abecedariusabout 8 years 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 &gt;1&#x2F;neuron, that&#x27;s a real surprise to me, but if it&#x27;s &quot;there&#x27;s plenty of mosaicism and it makes a real difference&quot;, then not.
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apathyabout 8 years ago
<a href="https:&#x2F;&#x2F;www.nature.com&#x2F;articles&#x2F;ncomms12484" rel="nofollow">https:&#x2F;&#x2F;www.nature.com&#x2F;articles&#x2F;ncomms12484</a><p>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&#x27;s all but unavoidable.
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tropoabout 8 years ago
Isn&#x27;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.
failrateabout 8 years ago
I wonder if this is involved in storing information in the brain.
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RangerScienceabout 8 years ago
Main paper:<p><a href="http:&#x2F;&#x2F;science.sciencemag.org&#x2F;content&#x2F;356&#x2F;6336&#x2F;eaal1641&#x2F;tab-pdf" rel="nofollow">http:&#x2F;&#x2F;science.sciencemag.org&#x2F;content&#x2F;356&#x2F;6336&#x2F;eaal1641&#x2F;tab-...</a><p>Unfortunately, looks like you have to register (&quot;free&quot;?) and sign-in to download the full text.<p>Other papers linked in article:<p><a href="http:&#x2F;&#x2F;www.cell.com&#x2F;neuron&#x2F;fulltext&#x2F;S0896-6273(16)00097-0" rel="nofollow">http:&#x2F;&#x2F;www.cell.com&#x2F;neuron&#x2F;fulltext&#x2F;S0896-6273(16)00097-0</a><p><a href="http:&#x2F;&#x2F;www.cell.com&#x2F;neuron&#x2F;fulltext&#x2F;S0896-6273(12)00273-5" rel="nofollow">http:&#x2F;&#x2F;www.cell.com&#x2F;neuron&#x2F;fulltext&#x2F;S0896-6273(12)00273-5</a><p><a href="http:&#x2F;&#x2F;science.sciencemag.org&#x2F;content&#x2F;350&#x2F;6256&#x2F;94&#x2F;tab-pdf" rel="nofollow">http:&#x2F;&#x2F;science.sciencemag.org&#x2F;content&#x2F;350&#x2F;6256&#x2F;94&#x2F;tab-pdf</a>
skosuriabout 8 years ago
Every single microprocessor in every computer is unique in its own way (small errors in production). It doesn&#x27;t mean we can&#x27;t compute with them, nor that the variation is useful or relevant.
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lngnmnabout 8 years ago
No meaningful parts (which encodes proteins and gene regulation) are different, however. Nature does not work that way.<p>Comparison of two genomes as two billions-bases-long strings is meaningless and yields nonsense due to waste and introns. Genome isn&#x27;t a uniform string in the first place.<p>Nothing to see here, except hipster&#x27;s self-praise and want for attention.
danjocabout 8 years ago
I was told in science classes that all of a person&#x27;s cells shared the same DNA. Now I learn, nobody ever actually tested to see if that was true. This is why people don&#x27;t trust you, science.
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