Molecular heterogeneity of naturally occurring sn-glycerol-3-phosphate dehydrogenase low-activity variants in...

Northern analyses of two low-activity sn-glycerol-3-phosphate dehydrogenase (Gpdh) alleles extracted from natural populations of Drosophila melanogaster showed that one of them, GpdhACyg22, produced wild-type levels of a normal sized (1.7-kb) mRNA but the other, GpdhAMB5, had very low levels of a 1.7-kb mRNA together with low levels of a transcript 200 bp larger. The two variant genes were cloned and sequenced. Compared with normal activity alleles, there were two nucleotide differences in the DNA sequence of GpdhACyg22 which were in first-codon positions and would be expected to give rise to Asn-13-->Tyr and Arg-272-->Cys substitutions. The second of these changes is most likely to account for the altered properties of the enzyme. In contrast, none of the nucleotide differences in GpdhAMB5 would give rise to amino acid substitutions, but a 76-bp deletion in the 5' region removed the 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 TATA box sequence in the insertion, but the 1.9-kb transcript had heterogeneous 5' ends that were not associated with substitute TATA box sequences. The two transcripts either are produced at a lower rate or are less stable than the normal mRNA.