11 min readConcept sheet1-mark MCQ on codons, a 2-mark question on features of the code, and a 3-mark question on frame-shift mutations or tRNA; also a NEET favourite

The genetic code, mutations and tRNA

The genetic code is a triplet code read without commas: 61 codons code for amino acids and 3 are stop codons. tRNA is the adapter that reads it.

Codons64 in all (4³); 61 code for amino acids; UAA, UAG and UGA are stop codons

Start codonAUG codes for methionine and also signals the start of translation

Who cracked itGeorge Gamow (triplet idea), Har Gobind Khorana (RNA of known sequence), Marshall Nirenberg (cell-free protein synthesis), Severo Ochoa (polynucleotide phosphorylase)

tRNA shapeClover-leaf in two dimensions; inverted L in three dimensions

Cracking the code

A codon is a group of bases in mRNA that stands for one amino acid. There are 4 bases but 20 amino acids. The physicist George Gamow argued that a two-base code gives only 4² = 16 combinations, too few. A three-base code gives 4³ = 64, which is enough. Har Gobind Khorana, an Indian-born scientist, devised a chemical method to make RNA with known combinations of bases. Marshall Nirenberg's cell-free system made proteins from such RNA. Severo Ochoa's enzyme, polynucleotide phosphorylase, helped make RNA of set sequence without a template. Together, they worked out the full codon table.

Salient features of the genetic code

Triplet: three bases make a codon; 61 codons code for amino acids, and 3 are stop codons (UAA, UAG, UGA).
Unambiguous and specific: one codon codes for only one amino acid.
Degenerate: some amino acids have more than one codon (e.g. UUU and UUC both code for phenylalanine).
Read contiguously in mRNA, with no punctuation (comma-less).
Nearly universal: e.g. UUU codes for phenylalanine from bacteria to humans. A few exceptions occur in mitochondria and some protozoans.
AUG has two jobs: it codes for methionine and acts as the initiator (start) codon.

What one extra or missing base does

Problem

A code is read three letters at a time, like the sentence SIT AND EAT HOT DAL. Show the effect of (a) inserting X after SIT, (b) inserting XYZ after SIT, (c) deleting the A of AND.

Working

Original: SIT AND EAT HOT DAL.
(a) Insert one letter: SIT XAN DEA THO TDA L. Every word after the change is wrong: a frame-shift.
(b) Insert three letters: SIT XYZ AND EAT HOT DAL. One extra word appears, but the rest reads correctly.
(c) Delete one letter: SIT NDE ATH OTD AL. Again, the reading frame shifts.

Answer

Inserting or deleting one or two bases shifts the reading frame and changes every later codon. Inserting or deleting three bases (or a multiple of three) adds or removes whole codons, and the reading frame after it is unchanged.

Point mutation vs frame-shift mutation

Point mutation (base substitution)One base pair is replaced by another. Only one codon changes, so usually just one amino acid changes (unless the new codon is a stop codon). Example: GAG → GUG in β-globin, glutamic acid → valine, giving sickle-cell anaemia.

Frame-shift mutationOne or two bases are inserted or deleted. The reading frame shifts from that point, so most later amino acids change and the protein usually does not work.

tRNA: the adapter molecule

Francis Crick proposed that an adapter must read the code and also carry the amino acid. This is tRNA, once called sRNA (soluble RNA). It has an anticodon loop, whose bases pair with the codon on mRNA. It also has an amino acid acceptor end, where its amino acid binds. Each tRNA is specific for one amino acid. A special initiator tRNA starts translation. There are no tRNAs for stop codons. On paper, tRNA is drawn as a clover leaf; in real three-dimensional shape it is a compact inverted L.

How to draw tRNA (clover-leaf model)

Draw a short straight stem at the top, with the 5′ end on one side and the 3′ end sticking out a little further on the other.
Label the 3′ end amino acid acceptor end.
Draw three loops: one on the left, one on the right and one at the bottom.
Label the bottom loop anticodon loop and write three bases in it as the anticodon, e.g. UAC.
Below it, show a short piece of mRNA with the matching codon, e.g. AUG, paired to the anticodon.

In real life

Because the code is nearly universal, a bacterium can read a human gene. This is how bacteria are used to make human insulin for people with diabetes.

Exam angle

2 marks: “What is meant by saying the genetic code is degenerate and unambiguous? Give an example of degeneracy.” Degenerate: one amino acid may have more than one codon, e.g. UUU and UUC both code for phenylalanine. Unambiguous: each codon codes for only one amino acid.

3 marks: “Explain a frame-shift mutation with an example. Why does inserting three bases not cause one?” Insertion or deletion of one or two bases shifts the reading frame, changing every later codon (e.g. SIT AND EAT → SIT XAN DEA T...). Three bases add or remove a whole codon, so the frame after it is unchanged.

2 marks: “Why is tRNA called an adapter molecule?” It reads the codon on mRNA through its anticodon and also carries the matching amino acid at its acceptor end. So it links the language of bases to the language of amino acids.

Remember it

Stop codons: U Are Away (UAA), U Are Gone (UAG), U Go Away (UGA).