u/Ill_Impact6838

James, Onsi, Stadler and Truman- comedy of errors-part 2

Hello everyone,we are covering James Tour's video titled - Evolution vs design

In last part , I covered on the topic signal network and how they were whining that such a complicated system of embryo formation in fruitfly couldn't have evolved naturally .

In second part , I am going to talk about their second point, TADs ( Topologically Associated Domains)

Here are the exact points regarding TADs (Topologically Associating Domains) they talk about

  1. TADs refer to groupings of chromatin—the complex of DNA and protein—that are bunched together and closer in three-dimensional space,in compact shape.

  2. Transcription factors need to find specific DNA sequences to regulate genes. TADs help solve this search problem by organizing the genome, preventing the "tangled mess" that would otherwise hinder the movement of biological machinery like RNA polymerase.

  3. Research, such as the paper by Dota et al., suggests that "intersegmental jumping" across 3D-proximal segments within TADs significantly speeds up the search process for transcription factors compared to simple diffusion.

  4. Optimal Compaction: Theoretical models suggest an optimal compaction parameter (gamma) for these domains, around 0.7. Empirical measurements of approximately 8,000 human TADs show that they align closely with this theoretical optimum, rather than being too collapsed or too open.

5)Evolutionary Dilemma: The panel noted that the formation of TADs requires specific code (a 19-nucleotide sequence), the CTCF protein, and cohesin rings driven by ATP hydrolysis. They argue that this system presents a challenge for undirected evolutionary theories because intermediate, less-optimized states might have been energetically costly or non-functional, offering no survival advantage until the system is nearly perfect. The speakers suggested that TADs are a hallmark of eukaryotic genomes and were likely a necessary evolutionary or design solution to manage the vastly larger genomes of eukaryotic cells.

My argument -

I found it strange. They are looking at complex TADs of mammals which require cohesin and ctcf proteins interaction. They said ( mainly Truman) that this system is irreducibly complex.

The things in actuality , are much different from what they are saying. Many eukaryotes lack the ctcf - cohesin based TADs. So it's reducible . Like nematodes completely deleted their ctcf gene ,they rely on different mechanism of tad formation. Only basal nematodes like Trichinella spiralis have ctcf.

Insects also lack cohesin- ctcf based TADs network as in higher vetebrates. Platyhelminthes also completely lack the ctcf gene ,like more derived nematodes. They are still surviving . Yeasts completely lacks TADs . Plants have TADs but not like that in higher vetebrates. Jellyfish and sponges also lack the vetebrates level cohesin -ctcf mediated TADs organisation.

They are shocked . Why? Bcoz how is it possible for TADs to spread throughout the genome ?

Well it's easy . Start from simple- cohesin is much older than ctcf. Ctcf gene evolved in common ancestor of bilateria. Over time it acquired mutations in its n terminal region ( front part) which acted as binding site for cohesin,hence helping in formation of TADs.

Ctcf binding sites in genome mainly exist in non coding regions of dna . In few exceptions,they can exist in coding regions. Initially in primitive genome only few such binding sites for ctcf protein could have existed. Then n terminal mutations in the gene made the affinity for this protein increase towards cohesin and form partial tad networks ( not complete) But the most important events in the evolution of so many binding sites for ctcf occured due to retrotransposons which carried ctcf binding sites by copy and paste mechanisms. Those organisms in which ctcf disrupted genes by copy and paste mechanisms were removed from the gene pool. Only those survived whose genes and regulatory elements weren't affected by this retrotranspositions. Also they spread by wgd events. Hence more cohesin ctcf interaction leading to more TADs formation.

Here are links of retrotransposition part

https://www.sciencedirect.com/science/article/pii/S0092867411015078

https://www.nature.com/articles/s41467-020-15520-5

Now creationist might ask ,how did not fully cohesin -ctcf tad genome could exist ? At one time in the past there weren't enough ctcf binding sites ,hence limited compaction of dna.

Nope ,other mechanisms of compaction of dna existed. It's just another extra mechanism that organisms benefitted from.

Finally , Truman says evolutionary novelty is a story . You require lots of energy ,dna ,proteins and finally a long time after over generations mutations fine tune a protein .Intermediate steps are detrimental.

This is laughable. Each step will be beneficial. If a gene gets duplicated,let's suppose ,how much energy is required to maintain it? Negligible. A huge amount of atp is required to maintain membrane transporters and other things. Am I correct ?

And James Tour as usual says that junk dna have functions

What do you all think of Truman ? Any more extra information on TADs ??

Btw ,can someone pls tell me that whether primitive systems require the same compaction parameters value as talked about here?

Waiting for all of your response.

reddit.com
u/Ill_Impact6838 — 12 hours ago

James,Onsi,Stadler and Truman - comedy of errors- part 1

Part 1

Hello there , yesterday I posted about a guy named Onsi Fakhouri. Recently he has been coming to Tour's channel along with Stadler and Truman complaining about different things like origin of life and evolution based topics

I am here referencing a video on James Tour's channel titled - Evolution vs design.

I am making a part wise post of the video. They talked about a lot of points.

So I am breaking each point into distinct parts to keep my post short and simple.

Ok ,let's go -

Topic- Fruit Fly Embryo Development & Signaling Networks

Onsi says the following points-

Precise Positional Information (3:52 - 4:14): The embryo successfully differentiates cells based on location along an axis with 1% resolution. He argues that such high-level accuracy is remarkable and essential for the embryo to develop correctly.

Sophisticated Signaling Networks (4:26 - 6:00): This resolution is achieved through a complex, multi-layered processing system involving maternal inputs and four "gap genes." He emphasizes that this is a highly engineered system designed to filter noise and maintain precision.

Quantitative Optimality (10:13 - 13:25): Drawing on the work of physicist Bill Bialek ( a biophysicist) and colleagues, they note that the gene regulatory network is tuned to an optimal state. Modeling suggests that the system requires exactly four genes to hit the 1% resolution target—three are insufficient, and five are unnecessary "overkill."This overkill statement is Onsi's.

The "Knobs" (10:20 - 10:34, 13:42 - 14:14): As explained by him ( Fakhouri) , the model assigns two specific parameters to each of these interaction paths. He says that when you aggregate these variables across the entire regulatory graph defined in the model, you arrive at approximately 56 adjustable "knobs" or parameters.

Physics-Based Modeling (10:20 - 10:34, 13:42 - 14:14): These parameters were identified by Bill Bialek and colleagues as they attempted to build a predictive, quantitative model that could account for how the embryo achieves its 1% positional resolution. The complexity of having to tune all 56 variables simultaneously is a key point in the speakers' argument regarding the difficulty of this system arising through purely undirected evolutionary processes.

The Problem of Evolutionary Tuning (13:42 - 14:14, 58:47 - 59:18): Onsi and his arguments are that with 56 different parameters ("knobs") to adjust, the complexity is so vast that it is mathematically implausible for random mutations and natural selection to have fine-tuned the system to this optimal state without a directed, purposeful cause.

He also says these - Because there are hundreds of nuclei floating in the exact same fluid, they are all competing for the same maternal signaling proteins (like Bicoid). He argues that trying to pass an accurate, uncorrupted chemical message through a chaotic, crowded soup of 100+ nuclei without it getting distorted or lost in molecular noise is mathematically implausible. He uses the "Every Nucleus Knows Its Place" Claim: He points out that despite this chaos, each individual nucleus reads the local concentration of proteins so precisely that it "knows" its exact position along the body axis within a 1% margin of error. He argues that this level of coordinate-mapping across hundreds of independent points simultaneously requires an upfront, engineered communication network.

I was like wth? Why did they pick up a modern gene regulatory network?

Also Truman's words

The Knowledge Problem (14:26 - 15:22): He argues that a random process, such as mutation, lacks the "foresight" to know in advance that specific genes are required for a regulatory network, meaning it must simultaneously avoid disrupting thousands of other genes while attempting to build the correct ones.

And yes ,these are direct words of Truman

What do you all think about this? And Onsi ? He is in a nutshell saying that the entire network is too complicated to have evolved. It's designed. Same old creationist rhetoric. So many parameters. Mutate a gene , and boom something bad is going to happen . Irreducible complexity.

Wanna hear all about your words. Edit - https://www.pnas.org/doi/10.1073/pnas.2402925121 It seems like onsi is talking about this paper.

reddit.com
u/Ill_Impact6838 — 3 days ago

A question for everyone.

Hi there , I have been seeing james tour bringing a new guy named Onsi Fakhouri who is claims to be a phd , astronomer and is Pivotal’s Senior Vice President of Cloud R&D since a few days ,to talk about topics on evolution and debunk it . Any opinions on this guy ?

James tour also recently posted a video yesterday with him ,Stadler and Truman Evolution vs Intelligence.

reddit.com
u/Ill_Impact6838 — 4 days ago