Quick check:

1. How does phenylketonuria indicate that genes exert their effects through the production of specific enzymes?

2. How does Beadle and Tatum`s experiment on neurospora support the one gene-one protein hypothesis?

3. Explain why the one gene-one protein hypothesis needed to be modified in the light of conditions such as sickle-cell anaemia.

4. Describe Beadle and Tatum’s experiment on Neurospora which led to the one gene-one enzyme hypothesis.

5. Explain how certain inherited metabolic disorders indicate that genes exert their effects through enzymes.

6. Discuss why the one gene-one enzyme hypothesis had to be modified.

7. Divide the text into an introduction, principal part and conclusion.

8. Express the main idea of each part.

9. Give a title to each part of the text and summarize the text in brief.

■Text 9. The Gene Code

Prokaryotes and eukaryotes share the same 'language of life'. Comparisons of DNA sequences with the corresponding protein sequences reveal that (with a few exceptions) an identical genetic code is used in both prokaryotes and eukaryotes. This means that bacteria can be genetically engineered to make human proteins. The universal nature of the code suggests that all living things are descended from a single pool of primitive cells which first evolved this code.

One of the most remarkable facts of life is that each cell in an organism contains all the information required to determine all the characteristics of that whole organism. This information is stored in DNA, and is known as the genetic code. Deciphering that code has been one of the major scientific breakthroughs of the twentieth century. It has given us an understanding of how genes function, and it has opened the way for most of the recent developments in genetic engineering and biotechnology.

Transcribing the genetic code from DNA to mRNA

The genetic code is held in the order of bases along the DNA molecule. Sections of DNA called cistrons (commonly referred to as genes) contain the information needed to make a particular polypeptide. However, DNA does not carry out polypeptide synthesis directly. When the DNA in а cistron is activated, the information is transferred to a molecule of ribonucleic acid (RNA) called messenger RNA (mRNA), which acts as a template for the synthesis of the polypeptide.

The central dogma of biology

The relationship between DNA, mRNA, and polypeptides in a eukaryotic I cell is often called the central dogma of biology.

• mRNA is made on a DNA template in the nucleus, in a process called 1 transcription.

• The mRNA then moves into the cytoplasm, where it combines with ribosomes to direct protein synthesis by a process called translation.

• When the information in a cistron is used to make a functional polypeptide chain by transcription and translation, gene expression is said to have taken place.

mRNA is made from the DNA template

mRNA is a large polynucleotide polymer, chemically similar to DNA but differing in that:

• mRNA consists of only one chain of nucleotides, not two

• mRNA contains the sugar ribose instead of deoxyribose

• mRNA contains the base uracil instead of thymine.

During transcription, DNA acts as a template for making mRNA by complementary base pairing. Thus a particular short sequence of DNA may be transcribed as follows:

DNA base sequence: TAGGCTTGATCG

mRNA base sequence: AUCCGAACUAGC

The triplet code: frame-shift experiments

Twenty amino acids make all the proteins in living organisms.

• If a code consisted of one base for one amino acid, only four combinations would be provided (there are four bases).

• If two bases coded for one amino acid there would be 16 (4²) possible combinations.

• A three-base (triplet) code provides 64 (4³) possible combinations, more than enough for all 20 amino acids.

Francis Crick and his co-workers confirmed that the genetic code is a triplet code. Using enzymes, they added or deleted nucleotide bases in the DNA of a

virus that infects bacteria. They found that when one or two bases were added or deleted, the viruses were unable to infect the bacteria. But when three bases were added or deleted, the virus was able to infect the bacteria. They concluded that adding or removing one or two bases caused a frame shift which inactivated the gene. However, adding or removing three bases only partially affected the gene. Thus the sequence of bases shown above would contain the following sequences of DNA base triplets and mRNA codons:

DNA base triplet sequence: TAG GCT TGA TCG

mRNA codon sequence: AUC CGA ACU AGC

If one base (for example, guanine) is added to the DNA the frame shifts and the sequence of triplets and codons is changed:

DNA base triplet sequence: GTA GGT TTG АТС G

mRNA codon sequence: CAU CCG AAC UAG С

The results of the frame-shift experiments also showed that the code is non-overlapping:

• Each triplet in DNA specifies one amino acid.

• Each base is part of only one triplet, and is therefore involved in specifying only one amino acid.

A non-overlapping code requires a longer sequence of bases than an overlapping code (see box): however, replacing one base for another has a small or no effect.

Cracking the genetic code

To crack the genetic code, scientists had to work out which of the 64 codons determined each amino acid. To do this, they made mRNA molecules with a known sequence of bases. This mRNA was added to a cell-free system that contained isolated ribosomes, radioactively labelled amino acids, and all the enzymes needed for polypeptide synthesis. The polypeptides that were synthesised were then analysed to determine their amino acid sequence.

The first synthetic mRNA molecule made was a chain of uracil bases and was called poly-U. The polypeptide chain synthesised from it contained only phenylalanine. It was therefore concluded that the codon UUU codes for phenylalanine.

The complete genetic code was confusion finally deciphered in 1966.