Computational Criteria for the Disablement of Human GAPDH Pseudogenes

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), the glycolytic enzyme, exists as an asymmetric homotetramer and is apparently a product of a single somatic gene. This protein is considered a moonlighting protein meaning that it exhibits functions typically ascribed to other proteins. The functions include cellular processes that involve gene expression and, intriguingly, those that are associated with membrane-binding. There are more than 60 human pseudogenes for GAPDH. These pseudogenes, by definition, are considered non-functional, although multiple transcripts for GAPDH have been reported, suggesting that one or more of these pseudogenes are active. To assess whether there is selective pressure to preserve these sequences, we developed criteria to identify whether or not disablement of these pseudogenes occurred. The criteria involve analysis of the structural features of the 1-helix of real and pseudo GAPDH proteins. This region is required for membraneassociation, a conserved property that may be lost in pseudogenes.