The codon that starts polypeptide synthesis is usually AUG, which codes for methionine. See how start codons differ in bacteria and eukaryotes.
The codon that starts polypeptide synthesis is called the start codon, and in most organisms it is AUG. AUG specifies the amino acid methionine and marks the exact point where the ribosome begins translating a messenger RNA. A few bacteria and mitochondria use alternative start codons, but AUG remains the standard signal across life.
Getting the start codon right matters because it sets the reading frame for the entire polypeptide chain. A one-base error at the start changes every codon that follows.
What a Start Codon Actually Does
A codon is a three-nucleotide sequence in RNA that specifies one amino acid or a stop signal. The start codon is the triplet that recruits the ribosome and the initiator transfer RNA to the beginning of the coding sequence.
Without a start codon, translation cannot begin in the right place. The start codon and the codons that stop polypeptide synthesis, called stop codons, mark the boundaries of the region that will be translated into protein.
The Standard Start Codon: AUG
AUG is the near-universal start codon in eukaryotes, archaea, and most bacteria. It encodes methionine, so the first amino acid added to a new chain is methionine, or formylmethionine in bacteria.
The initiator tRNA that reads AUG is different from the tRNA that inserts methionine in the middle of a growing chain. In eukaryotes, the small ribosomal subunit binds the 5' cap of the mRNA and scans until it reaches the first AUG in a good context, known as the Kozak sequence. Bacteria instead use a Shine-Dalgarno sequence to position the ribosome just upstream of the start codon.
If you have ever looked up what is the function of the ribosome in polypeptide synthesis, this is the step where it matters most. The ribosome places the start codon in its P site, pairs it with the initiator tRNA, and then begins linking amino acids together.
Alternative Start Codons in Bacteria and Organelles
Not every polypeptide begins with AUG. In bacteria, GUG, UUG, and occasionally AUU can serve as start codons, although AUG is still the most common choice. The context around the codon and the available initiation factors determine which one is used.
Mitochondria use a reduced genetic code and their own translation machinery. Human mitochondria can start translation at AUA and AUU in addition to AUG. Archaea mostly use AUG but sometimes accept GUG or UUG.
| System | Common start codons | First amino acid | Notes |
|---|---|---|---|
| Eukaryotic cytoplasm | AUG | Methionine | Scans from the 5' cap; Kozak context matters |
| Bacteria (for example, E. coli) | AUG, GUG, UUG, AUU | Formylmethionine | Shine-Dalgarno sequence positions the ribosome |
| Archaea | AUG, sometimes GUG or UUG | Methionine | Initiation machinery resembles eukaryotes |
| Human mitochondria | AUG, AUA, AUU | Formylmethionine | Uses a variant genetic code |
Comparing these systems explains why "start codon" is not always a synonym for AUG. The same table shows that the first amino acid can also differ between organisms.
Reading Frame and Direction of Translation
The start codon establishes the first triplet, and the ribosome then moves one codon at a time toward the 3' end of the mRNA. This is the polypeptide synthesis direction: messenger RNA is read 5' to 3', and the chain is built from the N-terminus to the C-terminus.
The ribosome adds each new amino acid to the C-terminal end of the growing chain. Because the mRNA template is read in only one direction, the order of amino acids is fixed by the order of codons.
Students often ask why is transcription necessary for polypeptide synthesis, and the answer is straightforward: ribosomes read RNA, not DNA. Transcription copies a gene into messenger RNA, and that RNA carries the start codon the ribosome needs.
Start Codon vs. Stop Codons
Translation ends at one of three stop codons: UAA, UAG, or UGA. These triplets do not encode amino acids. Instead, they recruit release factors that detach the finished chain from the ribosome.
- AUG — start codon; adds methionine
- UAA, UAG, UGA — stop codons; no amino acid added
A start codon and a stop codon together define an open reading frame. Mutations in the start codon can stop translation from beginning at the correct site, and some mutations cause the ribosome to skip the first AUG and start farther downstream.
Polypeptide Synthesis vs. Protein Synthesis
The difference between polypeptide synthesis vs protein synthesis comes down to what happens after translation. Polypeptide synthesis is the ribosome-catalyzed assembly of amino acids into a chain. Protein synthesis includes that step plus folding, chemical modification, and sometimes assembly into larger complexes.
A newly made polypeptide is not yet a working protein. Chaperones help it fold, enzymes may attach sugars or phosphate groups, and targeting signals can send it to a specific part of the cell.
Why the Start Codon Matters in Research and Medicine
Start codons are a focus in molecular biology, genetics, and drug development. Scientists engineer start codons to control where a protein begins, and they study alternative start codons to understand disease-causing mutations.
Changes in a start codon can shorten a protein, alter its function, or prevent it from being made at all. Anyone with questions about a specific genetic variant or treatment should consult a healthcare professional.
Frequently Asked Questions
What is the start codon for polypeptide synthesis?
AUG is the standard start codon in eukaryotes and most bacteria, and it codes for methionine. In bacteria, GUG and UUG can also start translation, and human mitochondria use a few additional options. AUG is the dominant start signal, but it is not the only one.
Do all organisms use AUG as a start codon?
No. Most organisms use AUG for the majority of their genes, but bacteria frequently use GUG or UUG and occasionally AUU. Mitochondria have their own variant genetic code and can begin translation at AUA or AUU as well. So AUG is the most common start codon, not a universal one.
What happens if a start codon is mutated?
If the AUG is changed, the ribosome may fail to start translation at that site and instead begin at a downstream AUG. That often produces a shorter or altered polypeptide. The effect depends on the gene, and some changes cause disease while others have little impact.
This page provides educational research information and does not replace medical advice, diagnosis, or treatment.