Regulation of glyceraldehyde-3-phosphate dehydrogenase: inheritance and biochemistry of a low-activity genetic variant in the platyfish, Xiphophorus maculatus.

Analysis of an electrophoretic variant coded by the glyceraldehyde-3-phosphate dehydrogenase-2 (GAPD2) locus of the platyfish (Xiphophorus maculatus) revealed that the variant allele produced a defective subunit. As a homotetramer (from tissue extracts of homozygotes), the variant enzyme had only 12% the activity of homotetramers specified by the normal allele. In heterozygotes the defective subunits aggregated with the normal subunits to produce hybrid tetramers in the amounts expected for equal production of the two subunits by the two alleles but with the activity reduction expected according to the subunit composition. The total activities of muscle extracts in heterozygotes were reduced to about 55% of normal, consistent with that expected if neither compensatory synthesis of allelic products of the GAPD2 locus nor the GAPD1 locus took place. This result implies that regulation of the production of this enzyme is constitutive (produced at maximal rate) or depends on a mechanism which does not recognize the functional activity of the gene products. The absence of detectable segregation distortion suggests that the variant had no significant effect on viability, and thus may be selectively neutral, though producing in several tissues an activity deficiency of 88% in homozygotes.