Human glyceraldehyde-3-phosphate dehydrogenase molecular evolution by sequence analysis and possible mechanism for amplification.

We screened two human genomic libraries and isolated 14 different clones, designated lambda G1 and EG1-EG13, homologous to human glyceraldehyde-3-phosphate dehydrogenase (GAPD) cDNA. Subcloning and sequencing these recombinant phages led us to classify them as five different pseudogenes (psi G1-psi G5). All these sequences show such features typical of processed pseudogenes as numerous mutations, insertions, and deletions. The identity of numerous mutated sites among these pseudogenes and the presence of two Alu sequences flanking both ends of psi G1 suggest that GAPD pseudogenes originated from a unique reverse transcribed mRNA followed by gene duplication. The rate of nucleotide substitutions per site per year for known GAPD functional genes is low both for the synonymous substitutions (1.87 x 10(-9] and for the nonsynonymous substitutions (0.12 x 10(-9] and indicates that the GAPD cDNA sequence is well conserved not only at the amino acid level, but also at the nucleotide level. The rate of nucleotide substitutions per site per year for GAPD pseudogenes shows a higher value (5.9 x 10(-9] and suggests that these pseudogenes do not have any functional role.