106 Cracking the Genetic Code

Key Idea: Scientists used mathematics and scientific experiments to unlock the genetic code. A series of three nucleotides, called a triplet, codes for a single amino acid.

The genetic code

Once it was discovered that DNA carries the genetic code needed to produce proteins, the race was on to "crack the code" and find out how it worked. The first step was to find out how many nucleotide bases code for an amino acid. Scientists knew that there were four nucleotide bases in mRNA and 20 amino acids in proteins. Simple mathematics (below) showed that a one or two base code did not produce enough amino acids, but a triplet code produced more amino acids than were found in proteins. The triplet code was accepted once scientists confirmed that some amino acids have multiple codes.

Number of bases in the code Working Number of amino acids produced

Single (41) 4 4 amino acids

Double (42) 4 x 4 16 amino acids

Triple (43) 4 x 4 x 4 64 amino acids

1. (a) How many types of nucleotide bases are there in mRNA?

(b) How many types of amino acids are there in proteins?

(c) Why did scientists reject a one or two base code when trying to work out the genetic code?

2. A triplet code could potentially produce 64 amino acids. Why are only 20 amino acids produced?

3. (a) Why was DNase added to the cell free E. coli extract?

(b) What would it have been difficult to crack the code if no DNase was added?

A triplet (three nucleotide bases) codes for a single amino acid. The triplet code on mRNA is called a codon.

How was the genetic code cracked?

Once the triplet code was discovered, the next step was to find out which amino acid each codon produced. Two scientists, Marshall Nirenberg and Heinrich Matthaei, developed an experiment (below) to crack the code. A cell free E. coli extract was produced for their experiment by rupturing the bacterial cells to release the cytoplasm. The extract had all the components needed to make proteins (except mRNA).

1 DNase was added to destroy bacterial

DNA so there was no template for mRNA to be made.

2

Radio-labelled amino acids and a synthetic mRNA strand containing only uracil (U) were added.

U UUUUUUU U UUU

Cell free E. coli extract.

Phe Phe Phe Phe 3

Once the mRNA was added an amino acid was produced. The codon UUU produced the amino acid phenylalanine (Phe).

4

Over the next few years, similar experiments were carried out using different combinations of nucleotides until all of the codes were known.