The fifth nucleotide (M-Cytosine) defeats Francis Crick's "Central Dogma"

-


Methylated cytosine is sometimes called the "5th nucleotide" because it is a modified form of the DNA base cytosine (C) that has a methyl group added to the 5th carbon atom of the cytosine ring. This modification, known as 5-methylcytosine (5mC), plays a critical role in epigenetics, the study of how gene expression is regulated without changes to the underlying DNA sequence.

5mC is one of the most abundant epigenetic modifications in eukaryotic genomes, and it is involved in a wide range of cellular processes among them being transposable elements (TEs), gBGC and AT mutational bias all major factors in genetic regulation and change for NonDarwinian adaptations. They are all natural cellular mechanisms as opposed to natural selection which is derivative of whole populations.

Epigenetic methylated cytosine can affect TEs, gBGC (GC-biased gene conversion) and AT mutational bias in a number of ways.

  • TEs (transposable elements) are mobile DNA elements that can move around within the genome. They can be either active or inactive, and their activity is often regulated by DNA methylation. Methylation of cytosines in TE promoters can repress their expression, while methylation of cytosines within TE bodies can promote their silencing. This can lead to new genes and adaptation without Darwin.

  • gBGC (GC-biased gene conversion) is a recombination associated process that tends to increase the GC content of recombining DNA over time. It is thought to be one of the major forces shaping the GC content in eukaryotes, particularly in mammals.

  • AT mutational bias is a phenomenon in which mutations from G/C to A/T are more common than mutations from A/T to G/C. This is thought to be due to the fact that methylated cytosines are more likely to deaminate, resulting in a transition mutation to thymine.

Overall, epigenetic methylated cytosine can have a significant impact on TEs, gBGC, and AT mutational bias. These effects can be complex and vary depending on the specific context. However, it is clear that DNA methylation plays an important role in shaping the mutational landscape of the genome.

The term "5th nucleotide" is not commonly used in scientific literature, but it is sometimes used in popular science articles and books. It is a useful way to describe 5mC because it emphasizes its importance as an epigenetic regulator of gene expression.

Additional information:

  • 5mC is generated by enzymes called DNA methyltransferases (DNMTs).

  • 5mC can be removed by enzymes called DNA demethylases.

  • 5mC patterns are dynamic and can change in response to environmental factors and developmental cues.

  • Disruptions to normal 5mC patterns have been linked to a variety of diseases, including cancer.

The "Central Dogma" of molecular biology is a theory stating that genetic information flows only in one direction, from DNA, to RNA, to protein, or RNA directly to protein. It was first proposed by Francis Crick in 1958, and has since become one of the most fundamental concepts in biology. The name "Central Dogma" was used to "poke the bear" with the catholic church.

The central dogma can be summarized in the following steps:


  1. DNA replication: DNA makes a copy of itself, so that each daughter cell inherits a complete copy of the genome.

  2. Transcription: DNA is transcribed into RNA. This process occurs in the nucleus of the cell, and involves the production of a messenger RNA (mRNA) molecule.

  3. Translation: mRNA is translated into protein. This process occurs in the cytoplasm of the cell, and involves the ribosomes.

The central dogma is a general principle, and there are some exceptions. For example, some viruses can use reverse transcriptase to transcribe RNA back into DNA. However, the central dogma remains a foundational concept in biology, and it helps us to understand how our genes are expressed and how proteins are made.

Crick combined the Central Dogma with NeoDarwinism to make a 50 year central axiom of evolution. Mainly mutations occur during DNA replication changing the proteins. If they are more fit, natural selection "fixes" that mutation.


However epigenetic methylation of cytosine bypasses the central dogma. It allows proteins to change the information in the DNA at the Cytosine, a direct violation of the one way flow of information from DNA > RNA > protein. 

Here are some other examples of how methylated cytosine can bypass the central dogma:

  • RNA editing: In some cases, methylated cytosine can be edited to thymine in RNA molecules. This is done by a class of enzymes called demethylating adenosine deaminase (ADAR) enzymes. ADAR enzymes can convert methylated cytosine (5mC) to uracil (U), which is then processed by the cell to thymine (T). This process of RNA editing can bypass the central dogma because it allows methylated cytosine to be translated into proteins even if it is not transcribed into mRNA.

For example, ADAR enzymes are used to edit the mRNA for the serotonin receptor 2C (5-HT2C) gene. Methylation of the 5-HT2C gene promoter can silence gene expression, but RNA editing can convert methylated cytosine to thymine, which allows the gene to be transcribed and translated.

  • Transposable element silencing: Transposable elements are mobile pieces of DNA that can insert themselves into new locations in the genome. Some transposable elements can be silenced by methylation. This silencing can prevent the transposable elements from being transcribed into RNA and translated into proteins. By silencing transposable elements, methylation can bypass the central dogma because it can prevent the expression of genes that are encoded by transposable elements.

For example, the Alu family of transposable elements is silenced by methylation in many cells. This silencing helps to prevent the Alu elements from disrupting important genes.

  • Epigenetic regulation: Epigenetic regulation is the process of controlling gene expression without changing the underlying DNA sequence. Methylated cytosine can be used to create repressive chromatin marks, which can prevent transcription factors from binding to DNA and initiating transcription. This means that methylated cytosine can be used to silence genes without changing the DNA sequence. By silencing genes, methylation can bypass the central dogma because it can prevent the expression of genes even if they are transcribed into mRNA.

For example, methylation of the promoter region of a gene can prevent transcription factors from binding to DNA and initiating transcription. This can silence the gene even if the DNA sequence is unchanged.


Methylation is a powerful epigenetic mechanism that can regulate gene expression in a variety of ways. By bypassing the central dogma, methylation can influence the expression of genes that are involved in many different cellular processes, including development, differentiation, and NonDarwinian rapid adaptation.

To conclude the "fifth" nucleotide, epigenetically Methylated cytosine defeats the 50 year reign of one of the most important axioms of evolution, the Central Dogma.

Comments

Post a Comment

Popular posts from this blog

No, the EES is not just a add on to Neo-Darwinism aka the Modern Synthesis

-
Image
" The summary of the state of affairs on the 150th anniversary of the Origin is somewhat shocking: in the post-genomic era, all major tenets of the Modern Synthesis fthe theory of evolution) are, if not outright overturned replaced by a new and incomparably more complex vision of the key aspects of evolution (EES). So, not to mince words , the Modern Synthesis is gone" -Eugene Koonin, an evolutionary biologist (Cited by over 270,000 evolutionary scientists.) The Extended Evolutionary Synthesis (EES) represents a significant departure from the traditional neo-Darwinian framework, also known as the Modern Synthesis . While both theories aim to explain evolutionary change, they differ fundamentally in their underlying mechanisms and the roles they assign to various biological processes. A crucial point of divergence lies in the interpretation and application of the term " evolutionary ," particularly concerning the incorporation of epigenetic mechanisms....
Read more

Is the random mutational model of evolution on its way out?

-
Image
While the random mutational model of evolution has long been a cornerstone of evolutionary biology, the Extended Evolutionary Synthesis (EES) and the study of epigenetics are challenging its core assumptions. The Random Mutational Model and Its Limitations The traditional view of evolution, often called the Modern Synthesis or neo-Darwinism , emphasizes random genetic mutations as the primary source of variation. Natural selection then acts upon this variation, favoring individuals with advantageous traits. This model has been successful in explaining some evolutionary phenomena, but it also has limitations: It struggles to explain complex adaptations: The idea that complex features like the eye or the immune system arose solely through random mutations seems statistically improbable. It overlooks the role of the environment: The traditional model treats the environment as a selective force, but it doesn't fully consider how organisms can actively respond to and s...
Read more

ERVs and Common Descent: A Reassessment in Light of Recent Findings

-
Image
Endogenous retroviruses (ERVs) have long been considered strong evidence for the common descent of humans and chimpanzees. These remnants of ancient viral infections, embedded in the genomes of both species, were once thought to be non-functional "junk DNA." The premise was that the shared presence of these seemingly random insertions in corresponding genomic locations could best be explained by a shared evolutionary history. However, recent research, such as the "Switching Sides" article published in May 2021, has challenged this assumption by demonstrating that ERVs play a functional role in the development of the human embryo and immune system. This discovery raises questions about the validity of using ERVs as primary evidence for common descent. The Traditional Argument for Common Descent The traditional argument for common descent based on ERVs rests on the following points: Random Insertion: Retroviral insertions are thought to occur randomly in...
Read more