The central dogma of molecular biology is the hypothesis that the main flow of information in cells is from DNA to RNA to proteins.
The main forms of information flow are (according to the central dogma and current research):
- DNA Replication: Information of parent DNA is passed on to child DNA.
- Transcription: DNA information is passed on to RNA as input into protein synthesis.
- Translation: RNA information is passed on to proteins.
The central dogma recognises that in rarer cases information may flow from RNA to DNA (for example HIV) and from parent RNA to child RNA (a common form of viral replication).
The central dogma hypothesises that other transfers (notably protein to protein, protein to RNA and protein to DNA) do not exist.
The dogma (suggested by Francis Crick in 1958) is now considered an over-simplification, but the concept still stands in the majority of situations.
The sequence of nucleotides in DNA forms a genetic code (or triplet code). This code can be read by the cell to synthesise proteins.
Each set of three bases in a DNA sequence (called a codon) codes for a single amino acid. The identity of the amino acid depends on the sequence of bases.
The base sequence G-G-A codes for the amino acid glycine.
The order of these triplets in a gene codes for an order of amino acids. This is used to create a polypeptide chain. From this, a protein is made.
All mRNA strands begin with start codons and end with stop codons.
The first codon of an mRNA strand is always the start codon.
The start codon is usually AUG and it codes for the amino acid methionine. In eukaryotes, methionine is always the first amino acid in the polypeptide chain.
Out of the 64 codons, three do not code for any amino acids. These are the stop codons. The stop codons signal the end of the mRNA strand, where the translation into protein ends.
UAG, UAA and UGA are the stop codons.
Start and stop codons are found in the DNA strands from which mRNA is transcribed. They are found at the beginning and end of the templates from which mRNA is transcribed. In DNA, thymine is used instead of uracil.
There are several unifying properties of the genetic code.
The code is degenerate: several different codons correspond to the same amino acid.
The sequences GCC and GCA both code for alanine. Leucine is coded for by six different codons.
The combinations of bases that make up the codons are non-random. Codons that code for the same amino acid usually differ by just a single base.
The code is degenerate, or redundant, but it is never ambiguous. One codon can never specify two amino acids.
The code is universal. Apart from a few exceptions, the codons for amino acids are the same in all organisms.
The code is non-overlapping and continuous. The codons are read in discrete groups of three, as shown in the diagram below.
UAGUUCGGAAAG is read UAG UUC GGA AAG, not UAG AGU GUU UUC etc.
During translation, the nucleotide sequences on mRNA are used to form a polypeptide chain.
Translation has three stages: initiation, elongation and termination. These names are also used in transcription for analogous phases.
Three types of RNA are involved in translation:
|mRNA||Carries the instructions (coded in the base sequence) for the amino acid sequence.|
|tRNA||Delivers the amino acids needed to build the protein.|
|rRNA||Ribosomal RNA and proteins form the ribosome. Ribosomes catalyse the formation of peptide bonds between amino acids|
tRNA is a relatively small nucleic acid. It is only 70-90 nucleotides long. Every tRNA molecule represents an amino acid using a region called the anti-codon. The anti-codon is complementary to the codon found on mRNA and is three bases out of the total 70 to 90 of the molecule.
The tRNA molecule carries the amino acid that the mRNA codon represents to the polypeptide chain. This amino acid is then added to the growing chain.
The first stage of translation is initiation.
Initiation begins when the small ribosomal subunit and the mRNA strand bind.
The first tRNA molecule is called the initiator tRNA. It always carries the amino acid methionine, so all polypeptides begin with this amino acid.
This is because the start codon on mRNA is always AUG.
The large ribosomal subunit can then bind to the mRNA strand. This completes initiation.
The ribosome holds the mRNA in place during elongation. It catalyses the formation of peptide bonds between neighbouring amino acids.
Polypeptide chains form during the elongation stage of translation. This is analogous to elongation in transcription.
Once the initiator tRNA and the ribosome have bound to the mRNA, a second tRNA molecule can bind to the next codon on the mRNA.
Only two tRNA molecules can bind to the ribosome-mRNA complex at one time. These tRNA molecules carry amino acids.
The ribosome causes peptide bonds to form between these amino acids, and so the chain grows.
Once the peptide bond is formed, the initiator tRNA separates from the ribosome. The ribosome moves towards the 3' end of the mRNA.
This process is repeated for the remaining codons. Another tRNA molecule binds with the next codon and adds another amino acid. The previous tRNA is then released.
Translation ends in termination. At this stage, the ribosome reaches the stop codon at the end of the mRNA coding sequence.
tRNA cannot bind to the stop codon because stop codons do not code for amino acids. Once the ribosome reaches the stop codon, translation ends.
The ribosomal subunits then break apart, releasing the polypeptide chain.
The new polypeptide may combine with other polypeptides or split into smaller fragments before becoming a functional protein.
It is possible for many ribosomes to bind to an mRNA chain along its length and simultaneously produce proteins.
The ribosome is a complex of ribosomal RNA (rRNA) and protein. It is essential for translation.
The ribosome holds the mRNA in place and catalyses the formation of peptide bonds between neighbouring amino acids on the elongating polypeptide chain.
The ribosome is made up of two subunits: the large and the small ribosomal subunits.
The small ribosomal subunit holds the mRNA strand in place, while the large ribosomal subunit forms the peptide bonds between the amino acids.
The ribosome has three tRNA binding sites: the E, P and A sites.
- The growing polypeptide chain is held in place by tRNA at the P site.
- The A site is where the next amino acid is delivered to the chain by tRNA.
- The E site is the exit site for tRNA that has given its amino acid to the polypeptide chain.
Firstly, the initiator tRNA enters the P site and the A site is vacant. Then a second tRNA carrying the next amino acid enters the A site.
The ribosome catalyses the bonding of this amino acid to the first, and the imitator tRNA is released from the P site.
Now the second molecule of tRNA moves from the A site to the empty P site and the next tRNA molecule enters the A site.
This process continues, and moves the ribosome towards the 3' end of the mRNA. When a stop codon is reached, the process ends.
Translation produces a chain of amino acids often referred to as a polypeptide. This polypeptide usually needs to be modified before becoming a functional protein.
The polypeptides may combine with others or split into smaller fragments before becoming functional proteins.
Some polypeptides have other molecules added to them, or they may be folded into different shapes.
The functions of proteins are strongly correlated to their shape, so these modifications are vital in the production of enzymes.
There are three main types of RNA, each of which serves a different role in protein synthesis.
- mRNA (messenger RNA) acts like a 'blueprint'. It is complementary to the sequence on a section of DNA. It carries the information about the sequence of amino acids required to build a particular polypeptide.
tRNA (transfer RNA) is a clover-shaped RNA molecule. It transfers amino acids to their positions in the polypeptide chain based on the mRNA code.
- rRNA (ribosomal RNA) is present in ribosomes and aids the synthesis of proteins. The ribosome is where mRNA and tRNA meet. The ribosome catalyses the addition of amino acids to the polypeptide chain.
RNA is involved in protein synthesis through the transcription (copying) of genes on DNA to mRNA and translation (conversion) of the transcribed mRNA into a polypeptide.