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Re:Theory Suggests That All Genes Affect Every Complex Trait by ancorevard on Wednesday June 20, 2018 @05:30PM (#17359971)
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.

Re:Theory Suggests That All Genes Affect Every Complex Trait by speby on Wednesday June 20, 2018 @06:02PM (#17360219)
#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. Ranging from things like height differences, leg lengths, intelligence levels, and a host of other characteristics, "identical" DNA does not mean physically identical creatures that look and behave exactly the same, even if they are far more similar than different.

Re:Theory Suggests That All Genes Affect Every Complex Trait by xyhopguy on Wednesday June 20, 2018 @06:13PM (#17360310)
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 by adrianN on Thursday June 21, 2018 @01:11AM (#17362314)
I think the interesting discovery has been that epigenetic traits can be inherited to some degree.
Re:Theory Suggests That All Genes Affect Every Complex Trait by NegativeLatency on Thursday June 21, 2018 @01:25AM (#17362353)
Neo-Neo-Lamarckism ;)
Re:Theory Suggests That All Genes Affect Every Complex Trait by thaumasiotes on Wednesday June 20, 2018 @08:11PM (#17361043)
> 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. Ranging from things like height differences, leg lengths, intelligence levels, and a host of other characteristics

New studies weren't needed; this has been known forever. From The Blank Slate:

> Even genetically homogeneous strains of flies, mice, and worms, raised in monotonously controlled laboratories, can differ from one another. A fruit fly may have more or fewer bristles under one wing than its bottlemates. One mouse may have three times as many oocytes (cells destined to become eggs) as her genetically identical sister reared in the same lab. One roundworm may live three times as long as its virtual clone in the next dish. The biologist Steven Austad commented on the roundworms' lifespans: "Astonishingly, the degree of variability they exhibit in longevity is not much less than that of a genetically mixed population of humans, who eat a variety of diets, attend to or abuse their health, and are subject to all the vagaries of circumstance -- car crashes, tainted beef, enraged postal workers -- of modern industrialized life." And a roundworm is composed of only 959 cells!

Re:Theory Suggests That All Genes Affect Every Complex Trait by dkural on Wednesday June 20, 2018 @08:51PM (#17361195)
The article above has nothing to do with Junk DNA. "All genes" is still about 1.5% of the genome. I think Junk DNA is a bad term for the parts of the genome that describe it. In human-engineered physical systems, we are used to all or most of the parts having a purpose of some kind, even if it is an aesthetic purpose.

The genome is more like source code that evolved over millions of commits, and has code from way back when, for different use cases. It also has "injected code" ie ancient viral DNA, and other weird artifacts that's not relevant to the functioning code base of today. Sure, it is useful from a meta-evolutionary perspective, those parts can be refashioned for another use... but so can real-world "junk" :)

Re:Theory Suggests That All Genes Affect Every Complex Trait by resource0x on Wednesday June 20, 2018 @09:03PM (#17361240)
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

Re:Theory Suggests That All Genes Affect Every Complex Trait by dkural on Thursday June 21, 2018 @10:42AM (#17365579)
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 showing you can survive with large chunks of it missing. Each human in fact has thousands of such structural variations.
Re:Theory Suggests That All Genes Affect Every Complex Trait by resource0x on Thursday June 21, 2018 @11:41AM (#17366148)
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 by dkural on Thursday June 21, 2018 @12:52PM (#17366871)
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 by resource0x on Thursday June 21, 2018 @06:46PM (#17369872)
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 by dkural on Thursday June 21, 2018 @09:58PM (#17370706)
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 by resource0x on Friday June 22, 2018 @03:07PM (#17376519)
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)

Re:Theory Suggests That All Genes Affect Every Complex Trait by dkural on Friday June 22, 2018 @04:39PM (#17377154)
While this is not my specialty, the field of "evo-devo" and developmental biology is the field trying to answer those questions. Honestly, we still know very little about how the genome results in morphology.

It is a lot more like a cellular automaton than anything else. From minute gradient differences inside the fertilized egg, recursively structure spreads out in very much a cellular automata like fashion. Cells respond to the bio-mechanical stress around them and to the signals they bathe in, to decide cellular fate, and in turn release new signals..

It's a very different paradigm of computation than the one we think of. Each cell is like a docker instance, containing the full source code. Perhaps these links explain a bit:

https://www.youtube.com/watch?v=RQ6vkDr_Dec https://www.youtube.com/watch?v=3mCgHK-X6lE https://www.youtube.com/watch?v=EaZOdrU1Du0

Re:Theory Suggests That All Genes Affect Every Complex Trait by resource0x on Monday June 25, 2018 @08:44PM (#17397101)
Analog computer switching to digital mode, and back to analog, and back to digital, etc... ? Something is extremely fishy here. Looks like highly intelligent series of operations, much beyond whatever we can imagine.
Re:Theory Suggests That All Genes Affect Every Complex Trait by ravinizme on Thursday June 21, 2018 @12:36AM (#17362199)
The coding part of the genes are 1.5% of the genomes.it is called the Exome.(32 millions) But when looking at all genes (including UTR, pseudogenes) from a basepair prespective It's closer to 40% of the genome.(1.2 billion bases)
Re:Theory Suggests That All Genes Affect Every Complex Trait by tejtm on Thursday June 21, 2018 @02:28AM (#17362624)
for No. 1 I will reuse a comment from a couple of years ago.

The term junk was intended to convey something apparently worth keeping (perhaps in the attic), as opposed to garbage, which is thrown away.

[0]https://news.ycombinator.com/item?id=1316152