Central Dogma – Definition, Replication, Transcription, Translation

What is the central dogma of molecular biology?

DNA is the full genetic information that determines the nature and function that an animal has. Proteins are made by the genetic code contained in DNA. Conversion of DNA encoded data to RNA is necessary to make proteins. So, in the majority of cells, genetic information is transferred from – DNA to RNA, and then to protein. The transfer of information is controlled by three different processes that help in the transfer of genetic information as well as its transformation into a different form:

1. Replication: A double-stranded nucleic acid is duplicated in order to create identical copies. This process preserves gene information.
2. Transcription: A DNA segment which is a gene transscribed and read to form a one-stranded segment of the RNA. The RNA is transferred from the nucleus to the celluloid.
3. Translation: The sequence of RNA transforms into amino acids in the process of forming the protein. In the process of translation the ribosome is able to read 3 bases (a codon) at each interval from the sequence of RNA, and transforms them into an amino acid.

The flow of information can be unidirectional, and indefinitely.

This is the most straightforward method of how is the Central Dogma of Molecular Biology is explained.

In the larger scheme, the fundamental doctrine that is molecular biological research provides the explanation of the transmission of genetic information in the biological system. It was first articulated in the work of Francis Crick in 1958, in the form of “Once the ‘information’ is passed into proteins, it is impossible to return to the protein. In further detail, the transfer details from nucleic acids to nucleic acids or from protein to nucleic acid might be possible, but the transfer of information from protein to protein or from nucleic acid to protein is not possible.”

What is the ‘Central Dogma’?

The Central Dogma is the method by which DNA’s instructions transform into a functional product. It was first suggested in the year 1958 by Francis Crick, discoverer of DNA’s structure.

• The principal tenet of molecular biology is the transfer of genetic information through DNA into RNA to create a functional product called which is a protein.
• The main dogma is that DNA has the necessary information to create the proteins we use and that RNA acts as the messenger that delivers these details into the ribosome.
• The ribosomes function as factories within the cell, where information is ‘translated into a functional product.
• The process through which DNA instructions are transformed into a functional product is known as gene expression.
• Expression of genes is achieved through two major steps – transcription as well as translatio.
• In transcription, the information contained in the DNA of all cells is converted into tiny portable messages in RNA.
• In translation, the messages are transferred from the point where the DNA is located in the cell nucleus to ribosomes from where they are read and translated into specific proteins.
• The central dogma says that the structure of information that occurs the most frequently in cells is:
  • With existing DNA, you can make the new DNA (DNA replication)
  • From DNA to create new transcripts of RNA (transcription)
  • From RNA to create the new protein (translation).

• Reverse transcription involves an exchange of information between RNA in order to create new DNA. This is the case with retroviruses, like HIV. It is the process through which genetic information derived from DNA is put together to form new DNA.

The Dogmas

The Dogmas provide a framework for understanding the transfer of sequence information between DNA, RNA, and protein, which are all information-carrying biopolymers. There are a total of nine conceivable direct transfers of information that can occur between these molecules.

The Dogmas classify these transfers into three groups of three:

A. Three general transfers:

1. DNA replication: This process involves the copying of DNA to produce an identical DNA molecule. It is the mechanism by which genetic information is faithfully transmitted during cell division.
2. Transcription: This transfer involves the synthesis of RNA using a DNA template. The enzyme RNA polymerase binds to a specific region of DNA and catalyzes the formation of an RNA molecule with a complementary sequence.
3. Translation: This transfer refers to the synthesis of proteins using the information encoded in mRNA. Ribosomes read the mRNA sequence and link amino acids together in a specific order to form a functional protein.

These general transfers are believed to occur normally in most cells and form the basis of the traditional understanding of the central dogma.

B. Three special transfers:

1. RNA replication: This transfer involves the copying of RNA from an existing RNA molecule. It was discovered by Howard Temin in 1970, who reported the existence of an enzyme called “RNA-dependent DNA polymerase” or reverse transcriptase. This enzyme can synthesize DNA using an RNA template.
2. Reverse transcription: This transfer occurs when DNA is synthesized using an RNA template. It is facilitated by the reverse transcriptase enzyme. This process was also reported by Howard Temin and David Baltimore in 1970 in certain RNA tumor viruses.
3. Protein synthesis without mRNA: This transfer refers to the synthesis of proteins directly from a DNA template without the involvement of mRNA. It challenges the traditional understanding of the central dogma, suggesting that the flow of information can be from RNA to DNA. This concept is known as “central dogma reverse” or teminism.

These special transfers, although known to occur, are not typical in most cells. They are observed under specific conditions, such as in certain viruses or in laboratory settings.

C. Three unknown transfers:

1. Protein copying from a protein: This transfer describes the hypothetical process of copying a protein to produce another protein. However, this transfer is not thought to naturally occur.
2. RNA synthesis using the primary structure of a protein as a template: This transfer suggests the synthesis of RNA using the sequence of amino acids in a protein as a template. Again, this transfer is not believed to naturally occur.
3. DNA synthesis using the primary structure of a protein as a template: This transfer speculates the synthesis of DNA using the sequence of amino acids in a protein as a template. Similarly, this transfer is not considered to naturally occur.

The unknown transfers represent hypothetical scenarios that have not been observed in nature or extensively studied.

Overall, the Dogmas provide a conceptual framework for understanding the flow of genetic information, but it’s important to note that the central dogma reverse and the unknown transfers are exceptions or hypothetical cases that deviate from the traditional understanding of information flow in molecular biology.

Central Dogma Steps – DNA to Protein

The process of DNA to protein, also known as the central dogma, involves several sequential steps. Here is a step-by-step breakdown of the central dogma, including the additional step of RNA processing or splicing:

1. Transcription: The first step in the central dogma is transcription. In this process, the genetic information stored in the DNA is copied into a molecule called messenger RNA (mRNA). The DNA double-strand unwinds, and an enzyme called RNA polymerase synthesizes an mRNA molecule that is complementary to one of the DNA strands. The mRNA molecule contains the same genetic information as the DNA but with uracil (U) replacing thymine (T).
2. Splicing: In eukaryotic cells, an additional step called splicing occurs after transcription. The primary transcript, or pre-mRNA, undergoes splicing to remove non-coding sequences called introns. The remaining coding sequences, known as exons, are spliced together to form mature mRNA. This process ensures that only the relevant coding sequences are retained in the mRNA.
3. Translation: The next step is translation, which occurs in the ribosomes. The mature mRNA, produced in the nucleus, is transported to the cytoplasm where it attaches to a ribosome. The ribosome reads the mRNA sequence in sets of three nucleotides called codons. The start codon AUG (coding for methionine) marks the beginning of the protein-coding region. Transfer RNA (tRNA) molecules, carrying specific amino acids, bind to the codons on the mRNA through complementary base pairing.
4. Initiation: The ribosome, along with initiation factors, recruits the appropriate tRNA carrying the first amino acid to the start codon on the mRNA. This initiation complex positions the tRNA in the ribosome, allowing protein synthesis to begin.
5. Elongation: During the elongation phase, the ribosome moves along the mRNA molecule, reading the codons one by one. Each codon specifies a particular amino acid, and the corresponding tRNA molecule carrying that amino acid binds to the codon. Peptide bonds form between adjacent amino acids, resulting in a growing polypeptide chain.
6. Termination: The translation process continues until a stop codon (UAA, UAG, or UGA) is encountered on the mRNA. When the ribosome reaches a stop codon, a release factor binds to the ribosome, and the newly synthesized protein is released.
7. Replication: The final step of the central dogma is replication, which involves the faithful duplication of the DNA molecule. Replication occurs during cell division and ensures the transmission of genetic information from parents to offspring. Enzymes called DNA polymerases unwind the double-stranded DNA helix and synthesize two new strands using each of the original strands as a template. The resulting two identical DNA molecules contain all the genetic information from the parental DNA strand.

Overall, the central dogma describes the flow of genetic information from DNA to RNA (transcription) and from RNA to protein (translation), with an additional step of RNA processing or splicing in eukaryotic cells. The process of replication ensures the faithful transmission of genetic information from one generation to the next.

Exceptions to the Central Dogma

While the central dogma of molecular biology provides a general framework for the flow of genetic information, there are exceptions to this principle. These exceptions challenge the straightforward sequence of DNA to RNA to protein. Here are some notable exceptions to the central dogma:

1. Retroviruses: Retroviruses, such as HIV, have an RNA genome and replicate by transcribing their RNA into DNA using a unique enzyme called reverse transcriptase. This reverse transcription step allows the retroviral RNA to be integrated into the host cell’s DNA. The process involves the conversion of RNA to DNA, which deviates from the central dogma. The information flow in retroviruses is RNA → DNA → RNA → protein.
2. RNA Viruses: Some viruses have RNA genomes and can directly utilize their RNA to produce proteins without the need for DNA intermediates. RNA viruses, like influenza virus or SARS-CoV-2, bypass the DNA replication step and synthesize proteins directly from their RNA genome. In these cases, the information flow is RNA → protein, which is contrary to the central dogma.
3. Prions: Prions are unique infectious agents composed solely of proteins. They can cause diseases like Creutzfeldt-Jakob disease and mad cow disease. Prions do not involve the transfer of genetic information from DNA or RNA; instead, they induce a conformational change in normal proteins, causing them to adopt an abnormal shape. This altered protein structure can lead to the misfolding of other normal proteins, resulting in disease progression. Prions follow a Protein → Protein information flow, which is distinct from the central dogma.

These exceptions highlight the complexity and diversity of biological systems, demonstrating that the flow of genetic information is not always strictly governed by the central dogma. Retroviruses, RNA viruses, and prions have unique mechanisms that involve unconventional pathways for the expression and transmission of genetic information. Understanding these exceptions expands our knowledge of molecular biology and the intricate ways in which genetic information can be processed and utilized in different organisms and infectious agents.

General transfers of biological sequential information

The general transfers of biological sequential information, as suggested by the Dogmas, encompass the processes of DNA replication, transcription, and translation.

1. DNA Replication: DNA replication is a crucial step in the central dogma as it ensures the transfer of genetic material to progeny cells. The process involves the replication of DNA to create an identical copy. A group of proteins called the replisome carries out this replication. The replisome includes components such as helicase, which unwinds the DNA, and DNA polymerase enzymes that synthesize new DNA strands based on the existing template strands. DNA replication primarily occurs during the S phase of the cell cycle.
2. Transcription: Transcription is the process by which genetic information stored in a section of DNA is replicated into a newly assembled molecule of messenger RNA (mRNA). Enzymes, including RNA polymerase and transcription factors, facilitate this process. In eukaryotic cells, the primary transcript is known as pre-mRNA, which undergoes additional processing steps such as the addition of a 5′ cap, a poly-A tail, and splicing to become mature mRNA. Alternative splicing can increase protein diversity from a single mRNA molecule.
3. Translation: Translation is the process where the information encoded in mRNA is utilized to synthesize proteins. In prokaryotic cells, transcription and translation can be linked, while in eukaryotic cells, the mRNA transcribed in the nucleus must be transported to the cytoplasm, where ribosomes bind to it. Ribosomes read the mRNA codons, and transfer RNA (tRNA) molecules carrying specific amino acids bind to the codons through their anticodons. The ribosome catalyzes the formation of peptide bonds between the amino acids, resulting in the synthesis of a polypeptide chain. The nascent polypeptide may undergo further processing, including folding, post-translational modifications, and association with other proteins or cofactors to form the mature protein.

These general transfers of biological sequential information—DNA replication, transcription, and translation—are believed to occur under normal conditions in most cells and constitute the core processes of the central dogma.

In contrast, the special transfers described by the Dogmas include RNA replication, reverse transcription (transfer of information from RNA to DNA), and direct translation from DNA to protein. These special transfers are observed in specific cases such as certain viruses (RNA replication, reverse transcription) or in experimental settings (direct translation from DNA to protein) and deviate from the typical flow of information in the central dogma.

Lastly, the unknown transfers, which are not thought to naturally occur, involve the hypothetical processes of protein copying from a protein, RNA synthesis using the primary structure of a protein as a template, and DNA synthesis using the primary structure of a protein as a template. These transfers have not been extensively studied or observed in biological systems.

Overall, the general transfers outlined by the Dogmas provide a comprehensive understanding of the flow of biological information from DNA to RNA to protein, forming the foundation of molecular biology and genetics.

Special transfers of biological sequential information

Special transfers of biological sequential information, as described by the Dogmas, involve unique processes that deviate from the typical flow of information in the central dogma. These special transfers include reverse transcription, RNA replication, and direct translation from DNA to protein.

1. Reverse Transcription: Reverse transcription is the process in which genetic information is transferred from RNA to DNA, contrary to the usual direction of transcription. This transfer occurs in certain organisms, such as retroviruses like HIV, as well as in eukaryotes during retrotransposon activity and telomere synthesis. Reverse transcription is facilitated by enzymes called reverse transcriptases, which catalyze the synthesis of DNA from an RNA template.
2. RNA Replication: RNA replication involves the copying of one RNA molecule to produce another RNA molecule. This process is observed in many viruses, where RNA-dependent RNA polymerases are responsible for copying RNA to generate new RNA strands. Interestingly, RNA-dependent RNA polymerases are also found in various eukaryotes, where they play a role in RNA silencing.
3. RNA Editing: RNA editing refers to the alteration of an RNA sequence through the action of protein complexes and guide RNA molecules. It can be seen as a transfer of information from one RNA molecule to another, leading to changes in the RNA sequence. RNA editing is a significant process that contributes to the diversity of gene expression and protein variants.
4. Direct Translation from DNA to Protein: In certain experimental conditions, direct translation from DNA to protein has been demonstrated in a cell-free system. Extracts from E. coli containing ribosomes, but without intact cells, were capable of synthesizing proteins from single-stranded DNA templates isolated from other organisms. This process occurred with the assistance of ribosomes and was enhanced by the presence of neomycin. However, it was unclear whether this mechanism of translation corresponded specifically to the genetic code, as further studies were required to determine the fidelity and specificity of this translation process.

These special transfers of biological sequential information showcase exceptional cases in molecular biology where the transfer of information occurs in non-traditional directions or in unique circumstances. They provide valuable insights into the versatility and adaptability of biological systems, expanding our understanding of the complexity of genetic information transfer.

Is the Central Dogma of Biology Unidirectional?

The Central Dogma of Biology is often described as unidirectional, emphasizing the flow of biological information from DNA to RNA and then to protein. However, this interpretation overlooks certain information transfers, such as DNA replication. To provide a more accurate understanding, it is important to refer back to Francis Crick’s original articulation of the Central Dogma in 1957.

According to Crick, the Central Dogma states that information transfers occur exclusively from nucleic acid (DNA and RNA) to either nucleic acid or protein. In other words, information flows from DNA to RNA through transcription and from RNA to protein through translation. This unidirectional flow covers the fundamental transfers of genetic information within living systems.

Crick’s version of the Central Dogma includes the conventional transfers that are widely accepted in molecular biology, such as transcription, translation, and DNA replication. These processes represent the primary routes of information flow in biological systems.

Additionally, Crick’s Central Dogma acknowledges the existence of a few “special transfers” that deviate from the unidirectional flow. These special transfers include reverse transcription, where genetic information is transferred from RNA to DNA, and RNA replication, which involves the copying of one RNA molecule to produce another. These special transfers represent exceptions to the typical flow described by the Central Dogma.

By recognizing Crick’s original formulation, we gain a more comprehensive understanding of the Central Dogma of Biology. It encompasses the essential transfers of genetic information while acknowledging the existence of certain special transfers that challenge the unidirectional nature of the flow. This nuanced perspective allows for a more accurate representation of the diverse processes involved in molecular biology.

Significance of the Central Dogma of Molecular Biology

The Central Dogma of Molecular Biology is a fundamental principle that describes the flow of genetic information within a biological system. It outlines the process by which genetic information is stored, replicated, and expressed in living organisms. The central dogma is composed of three major steps: DNA replication, transcription, and translation.

1. DNA Replication: This step involves the faithful duplication of the genetic material, DNA (deoxyribonucleic acid). During DNA replication, the two strands of the DNA molecule unwind, and each strand serves as a template for the synthesis of a complementary strand. This process ensures that genetic information is accurately passed on to daughter cells during cell division.
2. Transcription: Transcription is the process by which genetic information stored in DNA is converted into a complementary RNA (ribonucleic acid) molecule. RNA is synthesized based on the template provided by DNA. The enzyme RNA polymerase binds to a specific region of DNA called the promoter and catalyzes the synthesis of an RNA molecule with a complementary sequence to the DNA template. The newly synthesized RNA molecule, known as messenger RNA (mRNA), carries the genetic information from DNA to the site of protein synthesis.
3. Translation: Translation is the process by which the information encoded in mRNA is used to synthesize proteins. It takes place in cellular structures called ribosomes. Transfer RNA (tRNA) molecules carry specific amino acids to the ribosomes, where they bind to the corresponding codons on the mRNA molecule through base-pairing rules. As the ribosome moves along the mRNA molecule, amino acids are joined together in a specific order to form a polypeptide chain. The chain folds into a functional protein, which carries out various biological functions in the cell.

The significance of the Central Dogma of Molecular Biology lies in its role as a guiding principle for understanding the flow of genetic information and the fundamental processes that underpin life. It provides a conceptual framework for studying genetics, molecular biology, and the mechanisms of inheritance. The central dogma helps scientists investigate genetic diseases, gene regulation, evolution, and the development of new therapeutic approaches. Furthermore, it has been instrumental in the development of biotechnology and genetic engineering, enabling scientists to manipulate genetic information for various applications, such as producing recombinant proteins, designing genetically modified organisms, and gene therapy.

Central Dogma of Molecular Biology Cheat Sheet

FAQ

References

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