Species variation in the amino acid sequence of insulin

T HE INITIAL differences in amino acid sequences of some mammalian insulins as determined by Sanger and his co-workers [ 7-51 were confined to positions 8, 9 and 10 of the A chain of the molecule. (Fig. 1, Table I.) These changes in sequence produced no apparent change in the biological activity of the molecule. The limited number of amino acids involved suggested that the insulin could have arisen from a small number of single step mutations, but with so few examples it was not possible to deduce the direction in which the changes had occurred. (Fig. 2.) It was decided to analyze a larger number of species in the hope that greater variations in both sequence and biological activity might be found. The methods used were similar to those described for the earlier species comparisons [4-61, together with subtractive Edman degradations as modified by Konigsberg and Hill [7]. The amino acid sequence of insulin from a number of mammals and chicken are compared with the pig insulin sequence in Table II. Also included are two species of whale insulin determined by other workers [8,9]. In the course of analyzing rat insulin isolated from a large number of rat pancreases it was found that three components were obtained after oxidation with performic acid and electrophoresis at pH 9 in 1 per cent ammonium