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

Re: Theory Suggests That All Genes Affect Every Complex Trait

#111

Post by resource0x » Thu, Jun 21, 2018, 3:41 PM UTC

dkural wrote: post #110

resource0x wrote: post #67

Earlier quoted context omitted.

Quote: Male mice grow ovaries instead of testes if they are missing a small region of DNA that doesn't contain any genes, finds a new paper published in Science. Source: https://www.crick.ac.uk/news/science-news/2018/06/14/non-cod... EDIT: I think the finding is significant enough to warrant a separate discussion. Submitted a link: https://news.ycombinator.com/item?id=17361545

The press release is misleading - no one is claiming 98% of the DNA is "junk", contrary to what the press release claims with no evidence. Regulatory regions around genes are understood be crucial to gene function and taught in undergraduate education. Usually people claim that mobile elements + repetitive regions constitute the "junk" region, which is about 40% of the genome. Also, there are dozens of studies showin…

Not sure what you mean. Dawkins in 2009: “Leaving pseudogenes aside, it is a remarkable fact that the greater part (95 percent in the case of humans) of the genome might as well not be there, for all the difference it makes.”

The quote is all over the internet. E.g., see http://egnorance.blogspot.com/2013/02/richard-dawkins-on-jun...

Re: Theory Suggests That All Genes Affect Every Complex Trait

#112

Post by nonbel » Thu, Jun 21, 2018, 4:09 PM UTC

polski-g wrote: post #84

nonbel wrote: post #75

Of course, to me this is obvious: "everything correlates with everything else". Wait until we start seeing the results of the hyped up "gene editing" studies where they follow up for a few years and look at more than one/few outcomes at a time...

Don't even need that. Later this year BGI will allow you to submit zygotes and they'll provide a 23andme compatible report. And you can plug that in to dnaland and find out which zygote you should select for the most intelligent offspring.

Well that is almost surely fake. This is like a list of companies whose stocks should be shorted in (at what age is intelligence determined? 5 years?) as the lawsuits come rolling in.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#113

Post by dkural » Thu, Jun 21, 2018, 4:52 PM UTC

resource0x wrote: post #111

dkural wrote: post #110

Earlier quoted context omitted.

The press release is misleading - no one is claiming 98% of the DNA is "junk", contrary to what the press release claims with no evidence. Regulatory regions around genes are understood be crucial to gene function and taught in undergraduate education. Usually people claim that mobile elements + repetitive regions constitute the "junk" region, which is about 40% of the genome. Also, there are dozens of studies showin…

Not sure what you mean. Dawkins in 2009: “Leaving pseudogenes aside, it is a remarkable fact that the greater part (95 percent in the case of humans) of the genome might as well not be there, for all the difference it makes.” The quote is all over the internet. E.g., see http://egnorance.blogspot.com/2013/02/richard-dawkins-on-jun...

Huh! I've learned something.

Honestly, I have a PhD, doing human genomics, and to me Dawkins is a popular science writer. I don't know anyone in the field of genomics who is an actual working scientist who believes in the 95% number.

Note that the Encode Project defines functional as being transcribed, which is not a widely accepted definition of functional. The whole idea of "function" itself brings a lot of subjective notions into play.

As I said in the parent, I also think "junk dna" is a terrible term. What I prefer stating is, in agreement with Ohno/Kimura's theory of neutral selection, the vast majority of our genome is not under positive or negative selection - i.e. mutations occurring there are neither detrimental, nor helpful, for fitness.

If you look at allele ratios of variants across the genome, the vast majority show evidence of neutral drift.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#114

Post by ismail » Thu, Jun 21, 2018, 6:08 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…

“Distributes representation... there is no answer. It's certainly a trait of the sentence“

Thanks for this. Came here to post a comment and saw this Very similar view, with a different term.

Another way to define this is:

1. The higher level object/thing has traits/properties that the parts do not have

2. Understanding each part does not necessarily = understanding these traits

3. The parts are interdependent

4. The traits/properties of the higher level is determined by the interaction of the parts

... which is the definition of a system.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#115

Post by Ngunyan » Thu, Jun 21, 2018, 7:52 PM UTC

ismail wrote: post #114

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…

“Distributes representation... there is no answer. It's certainly a trait of the sentence“ Thanks for this. Came here to post a comment and saw this Very similar view, with a different term. Another way to define this is: 1. The higher level object/thing has traits/properties that the parts do not have 2. Understanding each part does not necessarily = understanding these traits 3. The parts are interdependent 4. The…

I think this is called an emergent property.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#116

Post by resource0x » Thu, Jun 21, 2018, 10:46 PM UTC

dkural wrote: post #113

resource0x wrote: post #111

Earlier quoted context omitted.

Not sure what you mean. Dawkins in 2009: “Leaving pseudogenes aside, it is a remarkable fact that the greater part (95 percent in the case of humans) of the genome might as well not be there, for all the difference it makes.” The quote is all over the internet. E.g., see http://egnorance.blogspot.com/2013/02/richard-dawkins-on-jun...

Huh! I've learned something. Honestly, I have a PhD, doing human genomics, and to me Dawkins is a popular science writer. I don't know anyone in the field of genomics who is an actual working scientist who believes in the 95% number. Note that the Encode Project defines functional as being transcribed, which is not a widely accepted definition of functional. The whole idea of "function" itself brings a lot of subject…

For fairness sake, quote from the same post (Dawkins changed his mind by 2012):

"So you can think of the protein-coding genes as being sort of the toolbox of subroutines which is pretty much common to all mammals -- mice and men have the same number, roughly speaking, of protein-coding genes and that's always been a bit of a blow to self-esteem of humanity. But the point is that that was just the subroutines that are called into being; the program that's calling them into action is the rest [of the genome] which had previously been written off as junk."

This makes sense to me (as a programmer :). But I wonder if someone managed to figure out the language in which the "caller" code is written. How does it say: call subroutine at position X, then if (condition), call subroutine at position Y, etc... I was not able to find any info on this.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#117

Post by foobarian » Thu, Jun 21, 2018, 11:37 PM UTC

kristianov wrote: post #96

foobarian wrote: post #62

Earlier quoted context omitted.

Reminds me of our corporate codebase after 10 years of A/B testing

Still growing strong I assume:)

We decided we had enough so we rewrote it! Well, most of it, there were some abandoned servlets that brought in enough money that we kept the old codebase running as well. :)

Re: Theory Suggests That All Genes Affect Every Complex Trait

#118

Post by chiefalchemist » Fri, Jun 22, 2018, 12:29 AM UTC

themodelplumber wrote: post #88

chiefalchemist wrote: post #78

Earlier quoted context omitted.

> "It makes intuitive sense if I think of traits as one outcome of a system." Put another way, if you were building something and you wanted it to survive, would you want a flexible multifaceted system, and not a dogma-esque checklist of X, Y and Z.

That's a great way to put it. You'd want a system that would instinctively re-implement patterns as a way of protecting itself, as well. I've noticed lately that if you take business process development, personal productivity, value-creation philosophy, socio-political framework-building (e.g. development of democracy) and combine that sort of thing with the traditional "software OR firmware OR hardware" definition o…

The humans sub-systems compliment each other and at the same time feels like backups of each other. The hardware of genes get adjusted by the software of epigenetics.

And who knows what we have yet to find. But it's making more and more sense in a why didn't we see this sooner sorta way.

Re: Theory Suggests That All Genes Affect Every Complex Trait

#119

Post by dkural » Fri, Jun 22, 2018, 1:58 AM UTC

resource0x wrote: post #116

dkural wrote: post #113

Earlier quoted context omitted.

Huh! I've learned something. Honestly, I have a PhD, doing human genomics, and to me Dawkins is a popular science writer. I don't know anyone in the field of genomics who is an actual working scientist who believes in the 95% number. Note that the Encode Project defines functional as being transcribed, which is not a widely accepted definition of functional. The whole idea of "function" itself brings a lot of subject…

For fairness sake, quote from the same post (Dawkins changed his mind by 2012): "So you can think of the protein-coding genes as being sort of the toolbox of subroutines which is pretty much common to all mammals -- mice and men have the same number, roughly speaking, of protein-coding genes and that's always been a bit of a blow to self-esteem of humanity. But the point is that that was just the subroutines that are…

That's a great question! As you know, DNA -> RNA -> Protein where the first arrow is transcription (polymerase) & the second one translation.

Genes are transcribed by a polymerase, and a couple of factors determine if the polymerase can be "recruited" there. Here are a couple of those factors:

1) Is the site accessible? That part of the genome needs to be "open chromatin" for it to be transcribed. Next question of course is what makes some chromatin open some closed..

2) Histone signals: DNA spools around wheel-like things called histones. Histones get marked in a variety of ways to indicate "status" of that part of the genome. Some of them are pro-transcription.

3) Polymerase is usually recruited there by DNA-binding proteins called "transcription factors". These proteins bind to the regulatory / "promoter" region upstream of a protein-coding gene. There are over a thousand different transcription factors, each with a specific "motif" they recognize.

The global state is detected in various ways (receptors on the cellular mebrane etc.), which triggers these transcription factors, which then go bind DNA near the genes, to activate a new subroutine.

Here's a paper: http://www.pnas.org/content/107/20/9186 Title: "Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks"

Re: Theory Suggests That All Genes Affect Every Complex Trait

#120

Post by resource0x » Fri, Jun 22, 2018, 7:07 PM UTC

dkural wrote: post #119

resource0x wrote: post #116

Earlier quoted context omitted.

For fairness sake, quote from the same post (Dawkins changed his mind by 2012): "So you can think of the protein-coding genes as being sort of the toolbox of subroutines which is pretty much common to all mammals -- mice and men have the same number, roughly speaking, of protein-coding genes and that's always been a bit of a blow to self-esteem of humanity. But the point is that that was just the subroutines that are…

That's a great question! As you know, DNA -> RNA -> Protein where the first arrow is transcription (polymerase) & the second one translation. Genes are transcribed by a polymerase, and a couple of factors determine if the polymerase can be "recruited" there. Here are a couple of those factors: 1) Is the site accessible? That part of the genome needs to be "open chromatin" for it to be transcribed. Next question of co…

Thank you, the article is fascinating indeed. But your explanation is not very accessible for a layman. I will tell you the questions a typical programmer will be asking: Main question: suppose we have to build a heart from scratch. It has certain shape, at every point inside it, there's a specific type of cell (they are all certainly different). E.g., there's a complicated network of blood vessels inside, and what not. There's a process that builds the heart. Question: who tells this process that at point (x,y,z), it should add a cell of type T, and connect it to neighbors in a certain way? Is it something like cellular automation, where the property of cell at (x,y) is determined by properties of neighbors only? All neighbors? And how this function is calculated? And what is the CODE for calculation? Where is it stored? And where something that was formerly called "JUNK", and now looks like a master program, fits into this picture?

To explain it to a programmer, it's better to avoid the terminology and specifics, but focus only on functional relations - e.g. type of cell at point (x,y) is a FUNCTION of types (or something) of cells (x-1,y), (x+1, y) and maybe something else. I can't find it anywhere.

BTW, I am not a believer in cellular automation stuff a la Wolfram, just trying to frame the question in a way I could understand.

(just in case you don't want to reply here, my fake email address is in my profile)