Genetic code
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Reading File
Reading File
Reading File
Reading File
Reading File
Here is a thorough overview of the genetic code, synthesized from multiple authoritative medical textbooks (Harper's Illustrated Biochemistry 32nd Ed., Thompson & Thompson Genetics and Genomics, and Emery's Elements of Medical Genetics and Genomics):
The Genetic Code
What It Is
The genetic code is the set of rules by which nucleotide triplets (codons) in mRNA are translated into amino acids during protein synthesis. It is the molecular "dictionary" that links the language of nucleic acids to the language of proteins.
Why Triplets?
- DNA has 4 nitrogenous bases (A, T, C, G / A, U, C, G in RNA)
- A 1-base code could encode only 4 amino acids
- A 2-base code allows only 4² = 16 combinations - not enough for 20 amino acids
- A 3-base (triplet) code allows 4³ = 64 combinations - more than enough for all 20 amino acids
Each three-nucleotide sequence on mRNA is called a codon.
The 64 Codons
| Codon Type | Number | Function |
|---|---|---|
| Sense codons | 61 | Code for the 20 amino acids |
| Stop (nonsense) codons | 3 | UAA, UAG, UGA - signal chain termination |
- Start codon: AUG (methionine) - initiates translation; also encodes internal methionines
- Most amino acids are encoded by multiple codons (see table below)
- Leucine and Arginine have the most codons: 6 each
- Methionine and Tryptophan have only 1 codon each - the least degenerate
The Genetic Code Table (Mammalian mRNA, read 5'→3')
| U | C | A | G | ||
|---|---|---|---|---|---|
| U | Phe, Phe, Leu, Leu | Ser, Ser, Ser, Ser | Tyr, Tyr, Stop, Stop | Cys, Cys, Stop, Trp | U,C,A,G |
| C | Leu, Leu, Leu, Leu | Pro, Pro, Pro, Pro | His, His, Gln, Gln | Arg, Arg, Arg, Arg | U,C,A,G |
| A | Ile, Ile, Ile, Met | Thr, Thr, Thr, Thr | Asn, Asn, Lys, Lys | Ser, Ser, Arg, Arg | U,C,A,G |
| G | Val, Val, Val, Val | Ala, Ala, Ala, Ala | Asp, Asp, Glu, Glu | Gly, Gly, Gly, Gly | U,C,A,G |
(First nucleotide = row, Second nucleotide = column, Third nucleotide = U/C/A/G within each cell)
Key Properties of the Genetic Code
As summarized in Harper's (Table 37-2), the genetic code has five defining features:
1. Degenerate (Redundant)
- Most of the 20 amino acids are specified by more than one codon
- The degeneracy is mainly at the third (wobble) position of the codon
- Example: all four codons beginning with GC (GCU, GCC, GCA, GCG) code for Alanine
- This provides a buffer against point mutations - a base change at the third position often still codes for the same amino acid
2. Unambiguous
- Each codon specifies one and only one amino acid (or stop signal)
- The code is degenerate but not ambiguous: given a codon → only one amino acid; given an amino acid → possibly multiple codons
3. Non-overlapping
- Codons are read sequentially without overlap - each nucleotide belongs to exactly one codon
- Reading proceeds strictly in triplets from a defined start point
4. Not Punctuated (Commaless)
- There are no "spacer" nucleotides between codons
- Once translation begins at AUG, the ribosome reads continuously, triplet by triplet, until it reaches a stop codon
- This means a single nucleotide insertion or deletion (frameshift) throws the entire reading frame off
5. Universal
- Virtually all living organisms - bacteria, plants, fungi, animals - use the same genetic code
- This is strong evidence for common ancestry of all life
- Notable exceptions: mitochondrial genomes use a slightly different code (e.g., in mammalian mitochondria, UGA codes for Trp instead of Stop; AUA codes for Met; AGA and AGG are stop codons instead of Arg)
The Wobble Hypothesis
The degeneracy at the third codon position is explained by Crick's Wobble Hypothesis:
- The tRNA anticodon pairs with the mRNA codon in antiparallel fashion
- Pairing at the first two positions of the codon is strict (Watson-Crick rules)
- At the third (3') position of the codon (= "wobble position"), non-standard base pairing is allowed
- Result: one tRNA can recognize more than one codon (differing only at the third base)
- This is why only ~30 cytoplasmic tRNA species suffice to read all 61 sense codons
tRNA - The Adaptor Molecule
- Each tRNA carries a specific anticodon (trinucleotide sequence complementary to a codon)
- Each tRNA is "charged" (aminoacylated) with its corresponding amino acid by aminoacyl-tRNA synthetases (at least 20 specific enzymes, one per amino acid)
- A given codon → recognized by exactly one tRNA species → delivers one specific amino acid
- tRNA molecules are 70-100 nucleotides long and share similar 3D structure
The Reading Frame
- Translation always begins at AUG (start codon), defining the reading frame
- The reading frame is the specific partition of the mRNA sequence into successive, non-overlapping triplets
- A frameshift mutation (insertion or deletion of non-multiples of 3 nucleotides) shifts the reading frame, typically producing a garbled or truncated protein
Codon Usage Bias
- Not all codons are used equally in all species or tissues
- tRNA levels in a cell mirror codon usage - frequently used codons correspond to abundant tRNAs
- This matters clinically: when producing recombinant proteins (e.g., insulin, erythropoietin) in non-human cells, codon optimization is often required to maximize expression
Sources:
- Harper's Illustrated Biochemistry, 32nd Ed., Tables 37-1 and 37-2
- Thompson & Thompson Genetics and Genomics in Medicine, 9th Ed., Table 3.1
- Emery's Elements of Medical Genetics and Genomics, Chapter 2
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