Mouse LDH-A functional gene and four different pseudogenes have been isolated. The complete sequence of 12,856 nucleotides of mouse genomic clone M15 containing LDH-A functional gene has been determined. The initiation sites of transcription and translation, and the putative regulatory sequences including the hexanucleotides CCGCCC and the cAMP-responsive sequence AAATCTTGCTCAA of mouse LDH-A gene have been identified. Seventeen human genomic clones containing the LDH-A functional gene and several pseudogenes have been isolated, and the exon-intron organization of human LDH-A functional gene of 12 Kb has been determined. The protein-coding sequence of the LDH-A genes from both mouse and human is interrupted by six introns. An additional intron was found in the 5' untranslated region, while there was no intron present in the entire 3' untranslated sequence. The relationships between the exon-intron organization of the LDH-A gene and the structural-functional domains of LDH-A protein are illustrated. The nucleotide sequences of LDH-A processed pseudogenes present in four different mouse genomic clone and two human genomic clones have been determined. A sequence comparison between LDH-A cDNA and processed pseudogenes revealed the types and rates of nucleotide changes, presumably without selection pressure, and these results have significant implications on spontaneous mutations and molecular evolution.
