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Comment by jboggan | Hacker News Reader

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.

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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?

> What if the cells of the brain have their own genome because each one of the billions of cells has a near specific specialized function.

That's the opposite of my interpretation -- it goes to show that even in the face of inevitable statistical noise, biological systems are incredibly fault-tolerant and durable. And furthermore, a neuron is just a neuron. It's unlikely that the genomic differences in a genius's neurons are significant compared to the overall genetic average which gave rise to a certain structure, certain proteins being more common, etc.

An interesting hypothesis, but difficult to reconcile with the surprisingly successful history of hemispherectomy [1]. Unless, perhaps, many unique neurons still serve nearly identical functions, despite their differences? Perhaps their uniqueness is a defense against disease, rather than functional specialization?

I don't mean "functions" in the sense of classic neuroscience, like specialized regions of the brain; I am using it as a very generic term, for lack of a better one.

[1] https://en.wikipedia.org/wiki/Hemispherectomy

> Could cellular function be that precise? Each micron of tissue the result of specific evolutionary pressures?

If that's what the data says.

It's probably an emergent quality from a set of simple rules being iterated. You can do a lot with a very very little if you're procedural about it.

z_(n+1)=z_n^2+C

I suspect that it's much like the immune system. For example, antibody diversity is "generated by DNA rearrangements during B-cell development".[0] And:[1]

> 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.

0) https://www.ncbi.nlm.nih.gov/books/NBK27140/

1) https://www.ncbi.nlm.nih.gov/pubmed/12558794

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...

Does your memory seem like it's big enough to require that much storage...?

Mine doesn't.

You hypothesis physically implausible - for starters, the speed at which memories are made and recalled is much, much faster than the timescale in which "writing" and "reading" of DNA happens.

While you can encode a lot of data in arbitrary arrangements of a molecule (just as you can encode a lot of data in e.g. arbitrary arrangements of magnetic polarity in a dense material) if you have the right tools to do that, our cells have different tools specialized to do different processing on DNA molecules. There's no evidence to suppose that these changes in DNA are somehow controllable by external factors as opposed to random variations, and there's no evidence to suppose that these changes in DNA are readable in any other way than the usual creation of proteins required for functioning of the cell.

The more we learn, the less we know.

More like, the more we realize how little we actually knew before.

The more we learn, the more our DNA knows.

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

One major trend over the past 20 years has also been the realization that "non-coding" regions tend to be anything but, their effects are subtle and still being discovered.

Nevertheless, it is long being observed that for example in cancer most mutations are passenger mutations. And this is true even more if they come from non-coding regions.

Honestly, I am a bit surprised that you claim to have a bioinformatics background and are surprised about somatic variants. I mean, they are observed everywhere in NGS (and used on a daily basis for tracking pluripotent stem cell clonality and other things), there is not much surprising about it anymore.

My unfinished PhD dissertation was about the topological differences in metabolic pathways expressed by various cancer cell lines in contrast to healthy tissue as a means of targeting metabolic "choke points" for future drugs - I'm not surprised about the existence of somatic variants but I am looking back and realizing how many of us were taking the uniformity of our systems for granted. Even when modeling the differences in a rapidly mutating cancer we always treated the variants as collections of discrete mutations that were uniform across the cluster. Then again this was ten years ago and you couldn't even think of sequencing enough lines to get at a cellular resolution. This really makes me want to pick that back up.

This is an argued area, but I think most people would agree that LTRs, which make up the bulk of non coding regions, have effectively zero effect on functional selection. There are many regions which are non-coding which appear to be under selection and play functional roles, but (and this belief only changed after looking into the problem in some detail) most of the LTR regions have no effect.

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

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.

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.

One of the fundamental techniques used by most varieties of mysticism is to make proclamations vague enough that they can be plausibly associated with any fact that is discovered later on. This is how mystics trick gullible people into believing that they have hidden knowledge. The trick is that these proclamations can't be used to make useful predictions; they only fit the data in hindsight.

You might want to look past the Deepak chopra types into the older mystery schools that don't solicit people's attention.

Such as?

Theravada Buddhism.

Hermeticism and derivatives of Egyptian mystery schools make for some interesting reading, and can be approached through academic avenues of archaeological/anthropological studies rather than woo-woo books and blogs. I'm definitely not suggesting it as an alternative to using scientific methods.

I find hermeticim fascinating, but I don't really see the connection. Where is hermeticism talking about genomes and neurons?

If I direct you to particular texts or ideas, then not only would I be falling into the trap of saying 'you should check out this spiritual technology, dude,' you'd be missing out on the exploratory and imaginative process that necessarily precedes discovery and innovation.

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.

I think you are being deliberately vague because you haven't anything except handwaving.

Once the mystics show some reproducible data it might make sense to listen what they have to say.

I'm not much of a mystic myself, but there is something to be said for seeking inspiration from non-scientific sources.

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.

Mysticism isn't trying to be a better science, any more than a guttering candle is trying to be a better laser pointer.

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