Only a few scientist have understood the passive role of DNA

As a gene-centric view of evolution, the modern synthesis has got causality in biology wrong

https://inference-review.com/article/evolution-in-revolution

Excerpt: "In discussing cell division, he points out that the genome is entirely passive. It is the cell that does the dividing. DNA is as much acted upon as acting. If so, the conventional framework of biological theory is misleading. “What is still a mystery,” Davies writes,
is the biological equivalent of the supervisory unit that determines when instructions need to switch to become passive data. There is no obvious component in a cell, no special organelle that serves as “the strategic planner” to tell the cell how to regard DNA (as software or hardware) moment by moment. The decision to replicate … is not localized in one place."



https://denisnoble.com/wp-content/uploads/2019/11/The-Dance-Sourcebook-1.pdf

Excerpts: "DNA is a completely passive molecule until it is activated by the organism to enable RNAs to be produced that in turn form templates for the production of proteins. DNA cannot even be transmitted faithfully until massively corrected by the organism. It is not therefore the ‘immortal replicator’. "

" One of the consequences of the relativistic view is that genes, defined as DNA sequences, cease to be represented as active causes. They are templates and are passive causes, used when needed to make more proteins or RNAs."

https://nautil.us/its-the-end-of-the-gene-as-we-know-it-7885/

Excerpt: "The modern synthesis has got causality in biology wrong … DNA on its own does absolutely nothing until activated by the rest of the system … DNA is not a cause in an active sense. I think it is better described as a passive data base which is used by the organism to enable it to make the proteins that it requires."

https://www.huffpost.com/entry/replace-the-modern-sythes_b_5284211

Excerpt: "The second reason is a much more conceptual issue. I think that as a gene-centric view of evolution, the modern synthesis has got causality in biology wrong. Genes, after all, if they're defined as DNA sequences, are purely passive. DNA on its own does absolutely nothing until activated by the rest of the system through transcription factors, markers of one kind or another, interactions with the proteins. So on its own, DNA is not a cause in an active sense. I think it is better described as a passive data base which is used by the organism to enable it to make the proteins that it requires."

My comment: Denis Noble is one those clever scientists who has understood the causality in biology; DNA is better described as a passive data base. It has no control over cellular mechanisms. DNA doesn't control life. DNA is not your destiny. DNA doesn't encode proteins, RNA does. DNA doesn't dictate phenotypes. I realized these facts after reading a few interesting articles about epigenetics, like this one:

https://www.genengnews.com/topics/omics/removing-epigenetic-post-it-notes-returns-stem-cells-to-unprimed-state/

Excerpt: "A drug originally intended to treat leukemia has an unexpected power. It can reverse stem cell development, converting primed pluripotent stem cells to naïve pluripotent stem cells. The drug, called MM-401, effectively removes epigenetic markers from histones, depriving the cell’s DNA-reading machinery of indications of where to start reading. Stripped of its accumulated “Post-it notes,” the DNA instruction manual is like new. It lacks any indications that any sections should receive any special attention."

Butterfly metamorphosis is a nightmare for the theory of evolution

The same DNA is in all four life cycles - DNA doesn't dictate phenotypes

https://darwinthenandnow.com/archives/1645/butterfly-nightmare/

Excerpts: "Why is the evolution industry silent on butterfly metamorphosis?

The answer is simple. Identifying a natural process for metamorphosis escapes a logical or, more importantly, a scientific explanation. The same DNA is in all four life cycles; the egg, the caterpillar (larva), the cocoon (pupa), and the adult butterfly. Metamorphosis, to the theory of Evolution, is a spectacular scientific enigma."

"Genetics determines the phenotype; it was thought. Francis Frick, British molecular biologist, biophysicist, and neuroscientist, called this the gene-centric theory of evolution, the “central dogma of molecular biology.” In theory, the form of a species, the phenotype, is determined by genetics (DNA), the genotype. The butterfly, however, defies Frick’s central dogma theory. During metamorphosis, the same genetics (DNA) produces different phenotypes. The evidence is clear: DNA does not exclusively control life. Evidence from the butterfly undermines the once-popular central dogma theory of evolution, the foundation of the Modern Synthesis (20th century) theory of evolution."

"This gene-phenotype butterfly nightmare, more amazingly, is ubiquitous throughout nature. As Italian geneticist, Giuseppe Sermonti, points out – “Examples of highly divergent forms possessing the same DNA are so conspicuous and so numerous that the marvel is that they have attracted so little attention.”"

Epigenetics

"The same DNA in different life-forms is called “genomic equivalence,” meaning that the control of the cell is beyond the DNA, or “epigenetic.” From a more comprehensive perspective, Brian Goodwin, a Canadian developmental biologist and principal founder of theoretical biology, argues –
“While genes are responsible for determining which molecules an organism can produce, the molecular composition of organisms does not, in general, determine their form.”"

About the mechanisms

https://www.frontiersin.org/articles/10.3389/fevo.2021.646281/full

"Epigenetics can explain the phenotypic diversity of insect larvae, pupae, and adults sharing a common genome because such mechanisms globally modulate gene expression rather than altering the DNA sequence (Belles, 2017; Glastad et al., 2019).

There are three major epigenetic mechanisms, one of which is the expression of microRNAs. These short, non-coding RNAs (18–24 bp) operate at the post-transcriptional level to inhibit the translation of specific mRNAs by base-pairing with the untranslated regions or occasionally the coding region (Asgari, 2013; Hussain and Asgari, 2014). Individual microRNAs can regulate the expression of single genes or hundreds of genes. The role of microRNAs in the regulation of complete metamorphosis in holometabolous insects is well-established (Belles, 2017; Ylla et al., 2017). The first microRNAs that are differentially expressed during lepidopteran metamorphosis have been identified in the greater wax moth Galleria mellonella (Mukherjee and Vilcinskas, 2014).

The two other principal epigenetic mechanisms regulate transcriptional initiation. The first is the acetylation and deacetylation of histones by enzymes with opposing activities, thus controlling the ability of transcription factors to access chromatin and initiate gene expression. The addition of acetyl groups to histones is mediated by histone acetyltransferases (HATs), which enhance access to DNA by loosening the chromatin, whereas the removal of acetyl groups by histone deacetylases (HDACs) has the opposite effect and therefore causes gene silencing (Marks et al., 2003). We have previously shown that histone acetylation/deacetylation modulates gene expression during the complete metamorphosis of G. mellonella (Mukherjee et al., 2012). The involvement of both histone modification and microRNAs in this process provides evidence for cross-talk between different epigenetic mechanisms (Mukherjee and Vilcinskas, 2014).

The final major epigenetic mechanism is DNA methylation (Glastad et al., 2019). The addition of a methyl group to a cytosine residue in the dinucleotide sequence CpG results in the formation of 5-methylcytosine, which retains the base-pairing specificity of the unmodified nucleoside but influences its interactions with regulatory proteins. The transfer of methyl groups to DNA is mediated by evolutionarily-conserved enzymes collectively known as DNA methyltransferases (DNMTs). These can be divided further into maintenance methyltransferases (DNMT1), which complete the symmetrical methylation marks on newly-replicated DNA by recognizing the hemimethylated sequences inherited from each parent, and de novo methyltransferases (DNMT3), which establish new methylation marks on unmethylated DNA (Bestor, 2000; Klose and Bird, 2006)."

My comment: Butterfly (insect) metamorphosis is a nightmare for gene centric evolutionary theorists and also for those who claim that DNA dictates organismal traits and charactersistics (phenotype). Butterfly metamorphosis clearly points out that DNA is just passive form of information and it does nothing without epigenetic control and regulation. Don't get lost, my friends.

Australian dragons' gender determined by epigenetic differences

Reptiles' sex is determined by the shape of chromosomes

https://phys.org/news/2022-01-australian-dragons-gender-epigenetic-differences-1.html?fbclid=IwAR2Ew-NbGn-iyHiRa5GMwO4IW2yhoM36Vo0QoZNJ7UH2eUGMSiu5I7A24pc

Excerpts: "Published today in PNAS, the study showed dragon lizards are determined to be male or female by epigenetic rather than genetic differences—that is, changes in the gene's chromosomal neighborhood rather than the gene itself."

"Professor Graves said the research team were astounded by the discovery.

"We looked at the genes of the sex chromosomes in both sexes, and could find no DNA sequence that distinguished them from each other. We couldn't understand why they weren't acting in the same way," Professor Graves said.

"It was particularly odd, because the two sex chromosomes look quite different under the microscope. The female-specific (W) chromosome has lots of highly repetitive (junk) DNA that stains brightly.

"Our breakthrough was the realization that this repetitive DNA might distort the W chromosome so that the sex gene was read incorrectly," Professor Graves said.
"So rather than sex being determined by the base sequence of a sex gene—like in humans, and every other animal we know about—in the dragon lizard it was about the gene's kinky chromosomal 'neighborhood.'""

""We would never have discovered this unique way of doing genetic sex determination if we'd just looked at humans, mice and zebrafish! Peculiar species like dragon lizards can provide new information about genes and gene regulation," Professor Graves said."

https://www.pnas.org/content/119/4/e2116475119

"We propose that altered configuration of the repeat-laden W chromosome affects the conformation of the primary transcript to generate more diverse and potentially inhibitory W-borne isoforms that suppress testis determination. This is a mechanism for vertebrate sex determination, in which epigenetic control regulates the action of a gene present on both sex chromosomes."

My comment: Researchers are surprised again. Genetic determinism just got long nails in the coffin. DNA doesn't determine organismal traits or characteristics. Could blind evolution develop a mechanism in which 3D shape of chromosomes affects sex determination? Certainly not. This discovery also contradicts with evolutionary ideas concerning assumed evolutionary steps from fish to amphibians to reptiles etc. But from the point of view of design, this kind of dynamic feature is very useful for reptiles in challenging environments. Evolution never happened.

RNA-editing is the most significant reason why DNA doesn't determine organismal traits and characteristics

DNA doesn't directly predict amino acid composition of the resulting gene products

http://www.columbia.edu/cu/biology/courses/w3034/Dan/readings/RNAediting-maas.pdf

Excerpts: "It was generally believed that the DNA-encoded, exonic sequence information stored in the genome directly predicts the amino acid composition of the resulting gene products. However, this view had to be modified following the discovery of RNA editing, a process that enables a cell to recode genomic information in a systematic and regulated manner, selectively changing the readout of a gene at single nucleotide positions within the primary RNA transcript."

"...the other type of RNA editing, which is characterized by base substitution, in pre-mRNAs of higher eukaryotes. Here the open reading frame is altered, yielding a protein with one or more changes in its amino acid sequence. Substitution RNA editing was detected in many mitochondrial RNAs of higher plants with mostly cytidine-to-uridine (C-to-U) or U-to-C changes. A recent systematic analysis of Arabidopsis mitochondrial genes revealed that 8% of all containing codons are edited documenting the widespread occurrence of C-to-U editing in higher plants. Table 1 lists the different types of RNA editing and some of their characteristics. In mammals, RNA editing is mainly represented by C-to-U and adenosine-to-inosine (which functions as guanosine) (Ato-I) conversions generating single amino acid changes in the resulting protein. This often has significant consequences for protein function. Among mRNAs that were found to undergo editing, the best-characterized examples are apolipoprotein B (apoB) transcripts (C-to-U change) and messages for neuronal glutamate and serotonin receptor subunits (A-to-I changes). Since the initial discovery of mRNA editing in mammals(6,7) more than a decade ago this process of posttranscriptional modification is now recognized as an important mechanism for generating molecular diversity."

Table 1. Different forms of RNA editing

"One gene many proteins

Eukaryotic organisms use several mechanisms to increase the number of functionally different proteins produced from a single gene. This includes alternative splicing of the exons, use of different promoters, translational frameshifting or posttranslational modification. As an additional level of variation, RNA editing allows for the expression of several protein variants at the same time, depending on the number and combination of modifications introduced into individual mRNAs."

RNA editing is regulated by complex epigenetic mechanisms

https://www.cell.com/molecular-cell/pdf/S1097-2765(17)30934-6.pdf

Excerpt: "N6 -methyladenosine (m6 A) and adenosine-to-inosine (A-to-I) editing are two of the most abundant RNA modifications, both at adenosines. Yet, the interaction of these two types of adenosine modifications is largely unknown. Here we show a global A-to-I difference between m6 A-positive and m6 A-negative RNA populations. Both the presence and extent of A-to-I sites in m6 A-negative RNA transcripts suggest a negative correlation between m6 A and A-to-I. Suppression of m6 A-catalyzing enzymes results in global A-to-I RNA editing changes. Further depletion of m6 A modification increases the association of m6 A-depleted transcripts with adenosine deaminase acting on RNA (ADAR) enzymes, resulting in upregulated A-to-I editing on the same m6 A-depleted transcripts. Collectively, the effect of m6 A on A-to-I suggests a previously underappreciated interplay between two distinct and abundant RNA modifications, highlighting a complex epitranscriptomic landscape."

Summary and conclusions:

• DNA-encoded, exonic sequence information stored in the genome doesn't directly predict the amino acid composition of the resulting gene products.
• RNA editing is now recognized as an important mechanism for generating molecular and proteomic diversity.
• Several epigenetic factors and mechanisms control and regulate RNA editing procedures.
• DNA sequencing made by analyzing cDNA strands should be questioned. Most of old research investigating DNA alterations is no longer valid.
• DNA is passive information and it has no predictive role over organismal traits and characteristics.
• These kind of complex regulatory mechanisms point to Intelligent Design and Creation.

Nutrition regulates the ability of flight within stick insects

An example of how epigenetic switching works

https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-021-05600-0

Excerpts: "A gene enrichment analysis for differentially expressed genes, including those obtained from winged vs wingless and flight vs flightless genes comparisons, revealed that carbohydrate metabolic process-related genes were highly expressed in the winged stick insect group. We also found that the expression of the mitochondrial enolase superfamily member 1 transcript was significantly higher in the winged stick insect group than in the wingless stick insect group. Our findings could indicate that carbohydrate metabolic processes are related to the evolutionary process through which stick insects gain the ability of flight."

"In this study, we compared the nutrient metabolic systems of flight-winged, flightless-winged and flightless-wingless stick insect groups using our midgut transcriptome data and those from public database and found the expression of transcripts related to the production of energy in carbohydrate metabolic processes in the winged stick insect groups."

"We estimate that different host plants would affect the expression profile of transcripts involved in the carbohydrate metabolic process in the insect midgut because the amount of nutrients depends on the condition and development of their host plants."

"We extracted genes with transcript per million (TPM) values higher than 2-fold for the subsequent gene set enrichment analyses. The examination of the differentially expressed genes in the flight and winged stick insects showed that the expression of 427 unique genes was elevated in the flight group, whereas the expression of 2636 unique genes was downregulated in the flight group."

"It is known that the flight fuel differs depending on the type of insect. The transition from rest to flight in many insects is accompanied by a 100-fold increase in the metabolic rate. Therefore, sufficient enzymatic activity is needed for the production of energy in flight. Short-distance-travel insects use carbohydrates as their main energy source. The preferred energy source of long-distance-travel insects is carbohydrates, and these insects then change their energy source from carbohydrates to lipids. In most insects, carbohydrates are used as the main energy source because carbohydrates are hydrophilic substances and move faster than lipids into insect bodies. Therefore, our findings might point to some gene expression bias in stick insects with evolutionary flight ability."

My comment: This is a typical example of an epigenetic mechanism that helps organisms adapt to changing environment. These adaptive changes have nothing to do with random mutations and they never result in any kind of evolution. These kind of mechanisms point to Intelligent Design and Creation. Don't get lost, my friends.