Sequencing and expression of the human ALDH8 encoding a new member of the aldehyde dehydrogenase family

The human aldehyde dehydrogenase gene (ALDH) family is characterized by two major conserved DNA sequences encoding residues which are possibly involved in the catalytic function and the maintenance of the functional conformation of the ALDH enzyme. This property is the basis for synthesizing the degenerate primers to clone several cDNAs of the ALDH isozymes. In this report, we describe the cDNA sequence and the expression of a new member of this family, ALDH8. The human ALDH8 gene was identified during the process of the screening for the human ALDH7 genomic clones. Overlapping ALDH8 cDNA clones were isolated by polymerase chain reaction (PCR) amplification of human salivary gland total RNA or lambda gt11 cDNA library. When the ALDH8 cDNA sequence was aligned with that of the ALDH7 which encodes a polypeptide chain of 468 amino acid (aa) residues, it was found that a termination codon (TGA) is placed in frame at the ALDH8 sequence corresponding to the codon GCG for the seventeenth aa position of the ALDH7. Therefore, the human ALDH8 gene is a potential nonprocessed pseudogene in the ALDH multigene family which has no other pseudogenes reported so far. Alternatively, the ALDH8 gene is a functional gene if the premature stop codon is suppressed, or if the first downstream in-frame ATG serves as the initiator codon. This longest putative open reading frame (ORF) encodes a polypeptide chain of 385 aa residues, includes the two ALDH conserved regions, and demonstrates 86% identity with the corresponding ORF region of the human ALDH7. The expression of the ALDH8 transcripts is restricted to the salivary gland among the human tissues examined.