12 THE BIOSYNTHESIS OF PROTEINS 



Other change in the rest of the chains. Comparison of haemoglobin G, A 

 and S further indicates that two contiguous amino acids can be replaced 

 independently as the result of two independent mutations, and that 

 mutational changes can occur in different regions of the molecule (Hunt 

 and Ingram, 1959, 1960; Hill and Schwarz, 1959). 



Haemoglobin A Val-His-Leu-Thr-Pro-Glu-Glu-Lys 

 Haemoglobin S Val-His-Leu-Thr-Pro-Fa/-Glu-Lys 

 Haemoglobin C Val-His-Leu-Thr-Pro-Lji-Glu-Lys 



Haemoglobin G Val-His-Leu-Thr-Pro-Glu-GZj-Lys 



Fig. 11. Amino acid sequence of the terminal part of the ^ chain in four 

 human haemoglobins (Hunt and Ingram, 1959; Hill and Schwartz, 1959). 



This established that the genetic material controls the nature and 

 position of certain amino acids in the polypeptide chains and makes one 

 suspect that the position of each individual amino acid of a polypeptide 

 chain might indeed be controlled by the gene. It would seem that the gene 

 responsible for the production of a given protein contains a set of instruc- 

 tions concerning the nature and positions of the amino acids in the 

 polypeptide chain, perhaps a complete blue print of the polypeptide chains. 

 One must then examine closely the fine structure of the gene and try to 

 decipher the indications it contains. 



2. Fine Structure of the Gene 



(a) Evolution of the notion of gene. Early studies in genetics revealed 

 that the genes — i.e. the determinants of certain morphological characters 

 — are often inherited in groups, as if they were linked together in some way. 

 The physical basis of linkage in higher organisms is the chromosome. In 

 Drosophila, for instance, there are four chromosomes in a haploid set, and 

 the genes fall into four linkage groups. Linked genes are located on the 

 same chromosome. The linkage is not absolute, however, for separation 

 and recombination between usually linked genes occur in a certain fraction 

 of the progeny. 



Crossing over can take place at many different points along a chromosome. 

 If the chances of crossing over were equal all along the chromosome, then 

 the frequency of recombination of two genes would be a simple function of 

 their distance on the chromosome : the further apart they would be located, 

 the more often would crossing over occur between them and the more fre- 

 quently would recombination be observed. It would be possible to compute 

 relative 'distances' between genes and the relative positions of the genes 



