Theory Suggests That All Genes Affect Every Complex Trait • Hacker News Board

Re: Theory Suggests That All Genes Affect Every Complex Trait

#41

Post by xyhopguy » Wed, Jun 20, 2018, 10:13 PM UTC

speby wrote: post #38

ancorevard wrote: post #26

Two things: 1. The theory of "junk DNA" of which the authors received Nobel Price is increasingly looking like...well...junk. 2. The recent discovery of Epigenetics adds a whole other dimension for understanding traits and genetics. Lots of biological science needs to be rewritten/updated in the years to come.

#2 is perhaps one of the most confounding recent areas of research that really starts complicating the study of DNA and how changes to it map to an organism's outcome in the real world over time and in different environments. As new studies emerge on identical twins/triplets/etc., it has become clear that even identical DNA does not at all have 100% clone of the person, even if they do in fact share the same DNA. Ran…

Eh I disagree. It's been known for a while that you need something other than just DNA to get the heterogeneity of cellular phenotypes. Remember that your Iris and toenails have the same DNA, yet wildly different gene expression profiles. Without cellular memory that would be impossible and we would all still be single celled organisms :)

Re: Theory Suggests That All Genes Affect Every Complex Trait

#42

Post by civilitty » Wed, Jun 20, 2018, 10:13 PM UTC

jds375 wrote: post #17

madhadron wrote: post #10

There's a couple of things that are slowly changing in the thinking of biologists related to this: 1. Genes are not loci. The "one gene = one protein" dogma of molecular biology (expanded: "one trait selectable in breeding experiments = one compact locus of the chromosome") was a priori wrong, but it's taken us decades to undo the damage. We were led astray because there are traits that do map to a single locus, or s…

Very interesting comment, thanks! Could you elaborate on what you mean by ‘evolution doesn’t abstract’? I did not totally understand what the example given had to do with abstraction

I think it's easier to understand if you rephrase it as "evolution doesn't encapsulate." Just because a bunch of smaller proteins fold into a bigger quaternary protein structure doesn't mean that those smaller proteins become "private" members of the new protein "class". Any chemical binding sites that are still exposed on the surface of the complex protein will still be chemically active and affected by evolutionary pressure. Even if you have a protein A made up of B, C, and D that all evolved together to metabolize fructose, an exposed binding site from protein C on A can still effect some completely unrelated biochemistry. At the same time, protein C could also be a critical component of a new protein E.

If the evolutionary pressures on E (or C individually) are greater than on A, C could evolve completely out from under A to the point where A is no longer functional or foldable. As such, evolution can't "rely" on abstractions like "protein C" because their "source code" can be changed nonlocally and their function is dependent on very local conditions like temperature, pH, and surrounding molecules. Abstracting away g(h(i(x))) as f(x) in Mathematica is pointless when your packet sniffer can arbitrarily change the meaning of "h(x)" to "nop".

Re: Theory Suggests That All Genes Affect Every Complex Trait

#43

Post by api » Wed, Jun 20, 2018, 10:14 PM UTC

deegles wrote: post #39

api wrote: post #4

Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer.

I wonder if years from now we'll look back at the "selfish gene" the way we look at Freudian ideas about psychology.

Definitely. I am generally unimpressed by Dawkins.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#44

Post by api » Wed, Jun 20, 2018, 10:16 PM UTC

aphextron wrote: post #13

api wrote: post #4

Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer.

>Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer. I'm really glad that this mental model I've built up seems to reflect reality. The idea of neatly editing specific genes to produce a desired resu…

Its not magic. Its just something we don't have good mental models for understanding since it doesn't resemble the things we usually engineer. I always give the following rough analogy:

"Imagine a programming language where every single instruction simultaneously executes and simultaneously alters the inputs of all other instructions to varying degrees."

Complex artificial neural networks and data flow models are closer to gene regulatory networks and the genotype->ribotype->phenotype causal flow but are still oversimplifications.

It is sometimes possible to hack individual genes to fix really glaring problems reducible to one or a few key mutations like sickle cell anemia. Those things are the low hanging fruit of genetic engineering. Beyond that it gets harder. Trying to do things like boost life span or median IQ will be exponentially harder and will require new cognitive paradigms IMHO.

Its too bad nobody studies this stuff anymore. There was a ton of really great research into complex systems and emergent behaviors in the 90s and 2000s and then it went out of vogue for some reason.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#45

Post by orasis » Wed, Jun 20, 2018, 10:21 PM UTC

If you look at how random projections work in machine learning or error correcting codes this makes perfect sense. The information is distributed across all bits.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#46

Post by bookofjoe » Wed, Jun 20, 2018, 10:22 PM UTC

politician wrote: post #35

bookofjoe wrote: post #21

Earlier quoted context omitted.

"We describe our first patient treated with lentiviral vector–mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells."

"We describe our first patient treated with into . ."

Or you could simply say "We performed a chemistry...":-)

Re: Theory Suggests That All Genes Affect Every Complex Trait

#47

Post by perl4ever » Wed, Jun 20, 2018, 10:27 PM UTC

aphextron wrote: post #13

api wrote: post #4

Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer.

>Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer. I'm really glad that this mental model I've built up seems to reflect reality. The idea of neatly editing specific genes to produce a desired resu…

Is it really magic or is the genetic code just defining something much more like a CPU or OS than an application program?

If you took a bug report and did a statistical analysis of what transistors contributed to the bug, in most cases it would tell you "pretty much all of them". In very rare cases, it would tell you there were specific broken transistors. Similar for OS instructions. Because it's just the wrong level to be analyzing problems with the ultimate behavior of a system that's mostly functional. 99.9999% of the time, you don't have a compiler bug or an OS bug or a hardware bug, because if you did, everything would be dead.

My kneejerk reaction* is that genes are like transistors or OS instructions and not like application program instructions, and it really shouldn't be surprising or mysterious if they don't correspond to specific behaviors. It's just a different level of abstraction.

*having not studied biology and genetics, and just assuming living organisms have to be like computers.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#48

Post by saalweachter » Wed, Jun 20, 2018, 10:43 PM UTC

perl4ever wrote: post #47

aphextron wrote: post #13

Earlier quoted context omitted.

>Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer. I'm really glad that this mental model I've built up seems to reflect reality. The idea of neatly editing specific genes to produce a desired resu…

Is it really magic or is the genetic code just defining something much more like a CPU or OS than an application program? If you took a bug report and did a statistical analysis of what transistors contributed to the bug, in most cases it would tell you "pretty much all of them". In very rare cases, it would tell you there were specific broken transistors. Similar for OS instructions. Because it's just the wrong leve…

The closest analogy in technology would be the Internet, IMO.

A CPU or a single computer is still a fairly homogeneous, consistent creation. Sure, it has a lot of transistors, but it's just the same pattern over and over.

Think about the Internet: many of the billions of things on the internet are similar enough to be called the same, but many of them are ... a little not. This computer is Intel, this is AMD. This one runs Microsoft, this one Ubuntu. This one Ubuntu 15.07 with a 5.3.2.2 Linux kernel, that one with a 5.3.7.1 kernel. This part uses IPv4, that IPv6. This HTML on this site is a little nonstandard, that one relies on an expired SSL certificate.

The body, and modifying it, is a lot like the Internet. You set up 1.1.1.1 as a DNS server and accidentally partition the Internet.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#49

Post by jds375 » Wed, Jun 20, 2018, 10:47 PM UTC

civilitty wrote: post #42

jds375 wrote: post #17

Earlier quoted context omitted.

Very interesting comment, thanks! Could you elaborate on what you mean by ‘evolution doesn’t abstract’? I did not totally understand what the example given had to do with abstraction

I think it's easier to understand if you rephrase it as "evolution doesn't encapsulate." Just because a bunch of smaller proteins fold into a bigger quaternary protein structure doesn't mean that those smaller proteins become "private" members of the new protein "class". Any chemical binding sites that are still exposed on the surface of the complex protein will still be chemically active and affected by evolutionary…

Great explanation (even though you're not OP), makes sense now!

Re: Theory Suggests That All Genes Affect Every Complex Trait

#50

Post by [deleted] » Wed, Jun 20, 2018, 11:17 PM UTC

madhadron wrote: post #10

There's a couple of things that are slowly changing in the thinking of biologists related to this: 1. Genes are not loci. The "one gene = one protein" dogma of molecular biology (expanded: "one trait selectable in breeding experiments = one compact locus of the chromosome") was a priori wrong, but it's taken us decades to undo the damage. We were led astray because there are traits that do map to a single locus, or s…

[deleted]