EVOLUTION OF THE CREATINE KINASES - THE CHICKEN ACIDIC TYPE MITOCHONDRIAL CREATINE-KINASE GENE AS THE FIRST NONMAMMALIAN GENE

In both mammals and birds, the creatine kinase (CK) family consists of four types of genes: cytosolic brain type (B-CK); cytosolic muscle ty pe (M-CK); mitochondrial ubiquitous, acidic type (Mi(a)-CK); and mitoc hondrial sarcomeric, basic type (Mi(b)-CK). We report here the cloning of the chicken Mi(a)-CK cDNA and its gene. Amino acid sequences of th e mature chicken Mi-CK proteins show about 90% identity to the homolog ous mammalian isoforms. The leader peptides, however, which are isoenz yme-specifically conserved among the mammalian Mi-CKs, are quite diffe rent in the chicken with amino acid identity values compared with the mammalian leader peptides of 38.5-51.3%. The chicken Mi(a)-CK gene spa ns about 7.6 kilobases and contains 9 exons. The region around exon 1 shows a peculiar base composition, with more than 80% GC, and has the characteristics of a CpG island. The upstream sequences lack TATA or C CAAT boxes and display further properties of housekeeping genes. Sever al transcription factor binding sites known from mammalian Mi-CK genes are absent from the chicken gene. Although the promoter structure sug gests a ubiquitous range of expression, analysis of Mi(a)-CK transcrip ts in chicken tissues shows a restricted pattern and therefore does no t fulfill all criteria of a housekeeping enzyme.