The Central Dogma of Molecular Biology is the foundational concept that describes the flow of genetic information within a biological system. This idea was first articulated by physicist and molecular biologist Francis Crick, one of the co-discoverers of the DNA double helix structure, in a 1958 paper and later restated in 1970. It proposes that information stored in deoxyribonucleic acid (DNA) is transferred to ribonucleic acid (RNA), and then used to construct proteins. This sequence—DNA to RNA to protein—explains how the code ultimately directs the function and structure of the entire cell. The core principle of the dogma is that once information has been incorporated into a protein, it cannot flow back to a nucleic acid.
Transcription: DNA to Messenger RNA
The first step in expressing a gene involves converting the DNA sequence into a complementary messenger RNA (mRNA) molecule in a process called transcription. This conversion is facilitated by the enzyme RNA Polymerase, which initiates the process by binding to a specific DNA sequence called a promoter. The double-stranded DNA helix unwinds and separates temporarily, exposing the nucleotide bases of the gene sequence.
RNA Polymerase uses one DNA strand, designated as the template strand, to synthesize a new RNA molecule. It reads the template strand in the 3′ to 5′ direction and builds the RNA transcript by adding new ribonucleotides in the 5′ to 3′ direction. The enzyme follows a strict base-pairing rule: adenine (A) on the DNA template is matched with uracil (U) in the RNA, and guanine (G) is matched with cytosine (C). This process continues until the polymerase encounters a termination signal, releasing the newly synthesized mRNA strand.
Translation: From RNA Code to Protein
Following transcription, the messenger RNA (mRNA) molecule travels to the cytoplasm, where its nucleotide code is translated into a specific sequence of amino acids to build a protein. This operation occurs on ribosomes, which are composed of ribosomal RNA (rRNA) and various proteins. The mRNA sequence is read in sequential sets of three bases, each triplet referred to as a codon, which specifies a single amino acid.
The decoding requires the assistance of transfer RNA (tRNA) molecules, which act as molecular adaptors. Each type of tRNA is linked to a specific amino acid at one end and carries a complementary three-base sequence, called an anticodon, at the other. When a ribosome binds to the mRNA, it moves along the strand, sequentially matching the mRNA codon to the corresponding tRNA anticodon. For instance, the start codon AUG initiates the polypeptide chain by being recognized by a tRNA carrying methionine.
As the ribosome moves, it aligns the incoming tRNA molecules, facilitating the formation of a peptide bond between the growing amino acid chain and the newly delivered amino acid. The ribosome possesses three binding sites, which ensure the tRNAs and mRNA are correctly positioned for chain elongation. This cycle repeats until the ribosome encounters one of the three stop codons (UAA, UAG, or UGA), signaling the release of the completed polypeptide chain.
The Biological Significance of the Central Dogma
The defined flow of genetic information is fundamental because it establishes a clear, hierarchical structure for how heritable information is expressed in every living cell. This structure ensures that the original genetic instructions stored in the DNA remain protected and stable, acting as a master archival copy. By separating the archival DNA from the temporary, working copies of RNA and the final protein product, the cell can precisely control which genes are active at any given moment.
The dogma provides a reliable, universal mechanism for the expression of genotype into phenotype, ensuring that the traits encoded in the DNA are faithfully translated into functional molecules. This uniform process across bacteria, plants, and animals underscores the deep evolutionary unity of life on Earth.
Revisions and Exceptions to the Original Idea
While the Central Dogma accurately describes the main route of information flow, subsequent discoveries revealed mechanisms that deviate from the strict DNA-to-RNA-to-protein pathway.
Reverse Transcription
One notable exception is reverse transcription, a process where genetic information flows backward from RNA to DNA. Certain viruses, known as retroviruses, including the human immunodeficiency virus (HIV), utilize an enzyme called reverse transcriptase to convert their RNA genome into a DNA copy, which then integrates into the host cell’s genome.
Prions
Another significant deviation involves prions, which are infectious proteins that transmit information through protein conformation rather than nucleic acid sequences. Prions cause neurodegenerative diseases by inducing a normal, non-infectious form of a protein to misfold into the pathogenic, disease-causing structure. This process represents a form of protein-only inheritance, where the pathogenic protein’s shape dictates the structure of other proteins, effectively transferring information without the involvement of DNA or RNA.