Allelic Complementation in the First Gene for Histidine Biosynthesis in SACCHAROMYCES CEREVISIAE. I. Characteristics of Mutants and Genetic Mapping of Alleles.

A number of his1 mutants were tested for suppressibility, for reversion by EMS, ICR-170, and nitrous acid, for their allelic complementation response, and for their temperature sensitivity and osmotic remediability. None of 52 mutants tested was suppressible by a known ochre suppressor. This is a very surprising result compared with other studies of suppressibility in yeast and suggests that another function essential to the cell is associated with the his1 gene product, the polarity effect of a nonsense mutation destroying the activity of the his1 enzyme and this second function.Sixty-four his1 alleles were ordered by allelic mapping methods utilizing gamma rays, X-rays, and MMS. The three maps agree well in placement of alleles and have been oriented on chromosome V of yeast with respect to the centromere. The 18 noncomplementing alleles are localized in the distal half of the gene, whereas the complementing alleles are distributed more or less evenly. Mutations which revert to feedback resistance map in the proximal end. Also at this end are mutations having a very high X-ray or MMS induced homoallelic reversion rate. This suggests that a number of missense mutations can occur in this region which result in innocuous amino acid substitutions in the enzyme. One X-ray map unit is estimated to correspond to about 131 base pairs or 43 amino acids, in agreement with results for the cytochrome-c protein obtained by Parker and Sherman (1969).