MOLECULAR HETEROGENEITY OF NATURALLY-OCCURRING SN-GLYCEROL-3-PHOSPHATE DEHYDROGENASE LOW-ACTIVITY VARIANTS IN DROSOPHILA-MELANOGASTER

Northern analyses of two low-activity sn-glycerol-3-phosphate dehydrog enase (Gpdh) alleles extracted fr om natural populations of Drosophila melanogaster showed that one of them, Gpdh(ACyg22), produced wild-typ e levels of a normal sized (1. 7-kb) mRNA but the other, Gpdh(AMB5), h ad very low levels of a 1. 7-kb mRNA together with low levels of a tra nscript 200 bp larger. The two variant genes were cloned and sequenced . Compared with normal activity alleles, there were two nucleotide dif ferences in the DNA sequence of Gpdh(ACyg22) which were in first-codon positions and would be expected to give rise to Asn-13 --> Tyr and Ar g-272 --> Cys substitutions. The second of these changes is most likel y to account for the altered properties of the enzyme. In contrast, no ne of the nucleotide differences in Gpdh(AMB5) would give rise to amin o acid substitutions, but a 76-bp deletion in the 5' region removed th e normal TATA box and there was a 20-bp insertion in the same region. One of the two transcripts was derived from the use of a substitute TA TA box sequence in the insertion, but the 1. 9-kb transcript had heter ogeneous 5' ends that were not associated with substitute TATA box seq uences. The two transcripts either are produced at a lower rate or are less stable than the normal mRNA.