Evolving Gene-Regulatory Networks

From the first paper cited:

" Because GRN topology is encoded directly in cis -regulatory sequence at its nodes, evolutionary changes in this sequence have great potency to alter developmental GRN structure and function. But there are many kinds of cis -regulatory change that affect function in different ways, ranging from loss of function, to quantitative change in function, to qualitative gain of function resulting in redeployment of gene expression."
So, what brings on "evolutionary changes in GRN cis-regulatory sequences?"
From the second paper cited:

“There are similarities between the developmental networks that build organ systems, called gene regulatory networks (GRNs), and the cellular networks that control behavior. One link is explicit: the development of the brain and specific neuronal subpopulations are encoded in the genome by GRNs.”
So, it would seem that altering GRN sequences could potentially also have an immediate effect on social behaviors?
From the third paper cited:

“Throughout evolution, regulatory networks need to expand and adapt to accommodate novel genes and gene functions. However, the molecular details explaining how gene networks evolve remain largely unknown. Recent studies demonstrate that changes in transcription factors contribute to the evolution of regulatory networks. In particular, duplication of transcription factors followed by specific mutations in their DNA-binding or interaction domains propels the divergence and emergence of new networks. The innate promiscuity and modularity of regulatory networks contributes to their evolvability: duplicated promiscuous regulators and their target promoters can acquire mutations that lead to gradual increases in specificity, allowing neofunctionalization or subfunctionalization.”
So, what kinds of things can effect GRN “adaptation” or "evolvability?"
From a fourth paper:

“The rewiring of gene regulatory networks can generate phenotypic novelty. It remains an open question, however, how the large number of connections needed to form a novel network arise over evolutionary time. Here, we address this question using the network controlled by the fungal transcription regulator Ndt80. This conserved protein has undergone a dramatic switch in function—from an ancestral role regulating sporulation to a derived role regulating biofilm formation. This switch in function corresponded to a large-scale rewiring of the genes regulated by Ndt80. However, we demonstrate that the Ndt80-target gene connections were undergoing extensive rewiring prior to the switch in Ndt80’s regulatory function. We propose that extensive drift in the Ndt80 regulon allowed for the exploration of alternative network structures without a loss of ancestral function, thereby facilitating the formation of a network with a new function.”
So, when a protein switches function, novel things happen. What leads to such changes in protein function? A slightly altered folding pattern might, for example.
These are just the first few footfalls down a path headed through, yes, fantastical territory, but which are at least analogous to known scientific findings, to the best of my knowledge. Obviously, I’m not going to be mistaken for a careful scientist by saying so, and please excuse my almost certain ignorance of what even seems possible, scientifically.


Again with the analogies:
A fifth paper:

(Psychoactive, hallucinogenic effects of ingested substances) " For centuries, Central American cultures considered Psilocybe mushrooms to be divine and used them for spiritual purposes. More recently, they have been called magic mushrooms and used for their hallucinogenic effects. These mushroom drugs may soon also be in use as pharmaceuticals that treat the existential anxiety of advanced-stage cancer patients, depression, and nicotine addiction. Their effects stem from tryptamines, which are chemical derivatives of the amino acid L-tryptophan and structural relatives of the neurotransmitters serotonin and melatonin. Among these, psilocybin is the primary chemical mushroom component. Psilocybin is an inactive precursor that is rapidly activated when consumed: splitting off a phosphate group results in the actual active ingredient, psilocin."
From an article:
“During their study, Hoffmeister and coworkers sequenced the genomes of two mushroom species to identify the genes that govern fungal enzymatic production of psilocybin. They further used engineered bacteria and fungi to confirm the gene activity and exact order of synthetic steps. This process includes a newly discovered enzyme that decarboxylates tryptophan, an enzyme that adds a hydroxyl group, an enzyme that catalyzes phosphorylation, and an enzyme that mediates two sequential amine methylation steps. With that knowledge in hand, the team designed a one-pot reaction using three of the enzymes to prepare psilocybin from 4-hydroxy-L-tryptophan.”

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What’s more fantastical about that than what is fantastical about regular biology?

You do realize that proteins adopt radically different conformations in response to routine physiological changes, don’t you? Say, with every beat of your heart?

Change in function doesn’t equate to repeated change in conformation performing the same repeated function, does it?

That’s not what your references are talking about. What leads to changes in the functions of these particular proteins is just a change in cis-regulatory sequences, not in the proteins.

I’m not seeing what you’re excited about here. You don’t seem to say.

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Working towards a full-orbed theory of the “Fall,” a theological idea that had real world consequences. While a willful, spiritual act, it nevertheless had physical, real world components.
" So, it would seem that altering GRN sequences could potentially also have an immediate effect on social behaviors?"
I have had resistance from others even attempting to go down this path --much less calling out that such a path is explorable.

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I can see why. It’s crazy. First, it demands a genetic Adam and Eve. Second, it demands the God produces simultaneous somatic and germline mutations. Third, it demands that the changes have effect on brain structure immediately in full-grown individuals, when what is described in your papers is changes in gene regulation during development. Fourth, these changes in behavior, if we stick to the story, would have been a result of the serpent’s persuasion, not anything God did.

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And why would it happen anyway? Someone eats an apple, and then some sort of supernatural force beams out in all directions and into the genomes of different organisms and cause mutations? Why? What a weird thing to believe.

Somehow this magical force that emanates out from two people eating an apple penetrates through everything unobstructed by miles and miles of rocks, water, and air, goes through layers of organic molecules in some organism’s cells, and then this force somehow magically knows it’s met a carbon atom that’s part of a DNA molecule in a still living cell, and decides to cause a mutation, and knows what the effect of it will be? And it went for a gene regulatory element because… that’s clearly what supernatural forces in magical apples do?

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If you guys had the slightest clue, I might even learn from what you have to say.
As it is, you’re more intent on mocking what you don’t understand, than in attempting to understand the reasonable inferences here. Go hound some other poster, please.
By no means does it require a genetic Adam and Eve. Nor an apple. :o)

Your “reasonable inferences” are based on misunderstandings of the papers you use for support. Was that not clear?

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Was I not clear that I’m not attempting to do what you think I am?

I don’t think you have a clear notion of what you’re attempting to do or of the requirements of such a thing or of what your supposed supporting literature actually says.

That’s quite obvious to me, because you are prone to think of me that way.
Shoe on the other foot.
Could the kinds of changes I’m considering lead an adult brain to (relatively) suddenly begin to interpret their environment in an unfamiliar way? I’m contemplating the kinds of changes that would lead to heritable mood alteration, due to GRN changes that get passed on.
I’m not from the camp that thinks Adam and Eve’s sin permanently marred all of God’s good creation; just their lasting perception of it.
I don’t really have to stretch very far to note that psychoactive substances can already accomplish this, at least temporarily, if not permanently once a habit is formed.
But, I’m thinking of something perhaps more lasting and heritable.
It’s nowhere near as outlandish a notion as some might prefer.

No. And it isn’t clear what kind of changes you think you’re talking about. Do you refer to simultaneous, identical mutations in every single cell of the adult brain? Or what?

That’s your misunderstanding. And that’s because you don’t understand what your notion is or much about biology.

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Seriously, dude… just shut it.
No, I’m not thinking of simultaneous mutations in every cell of an adult human’s brain or body.
Brain physiology depends on any number of coordinated variables working in concert. Very few unusual chemicals pass through the brain barrier, but the few that do can have a profound effect, systemwide, if plentiful enough. If the hypothetical change envisioned simultaneously affects the GRN in new sperm produced by the male, you can have a heritable pathway brought on by a single conscious act.
An analogy, but not at all exactly what I’m proposing, is the gaining of syphilis, which works slowly but surely.

How is it different?

Please explain the point you seem to be trying to make using G proteins and G protein-coupled receptors, which would IMO be one of the few mechanisms that @Guy_Coe could even consider trying to fit in this case.

What is the mechanism by which you propose a conscious act causing mutations? What is the mechanism by which all a male’s sperm inherit those mutations? How are any of the papers you have cited relevant to this fantasy?


How about just explaining it using repetitious muscle contractions? That requires repeated change in conformation, and doesn’t involve performing a novel function.

I am exploring the topic of novelly-introduced enzymes in relation to this topic. The paper I cited were meant as analogies, not precise mechanisms. But in that vein, it seems as though even you can conceive of a mechanism which makes this something other than a mere fantasy. Thanks for at least trying to understand my purpose.