Organization of the gene for an invertebrate mitochondrial creatine kinase: comparisons with genes of higher forms and correlation of exon boundaries with functional domains.
Two major gene duplication events are thought to have taken place in the evolution of creatine kinases (CK) in the vertebrates - (1) the formation of distinct mitochondrial (MiCK) and cytoplasmic forms from the primordial gene and (2) subsequent formation of the sarcomeric (sar-) and ubiquitous (ubi-) isoforms of octameric MiCK and muscle (M) and brain (B) isoforms of dimeric, cytoplasmic CK. The genes of these two CK clades reflect a distant divergence as sar- and ubiMiCK genes consistently have nine protein-coding exons while M- and B-CK genes have seven protein-coding exons; these genes share only one common exon. CKs are also widely distributed in the invertebrates and it has recently been shown that MiCKs evolved well before the divergence of the major metazoan groups. In the present communication, we report the structure and topology of the gene for MiCK from the protostome marine worm Chaetopterus variopedatus. The protein-coding region of the gene for this primitive MiCK spans over 10 kb and consists of eight exons, the last five (E4-E8) have identical boundaries to the corresponding exons of sar- and ubiMiCK genes. Exon-3 of the C. variopedatus MiCK gene consists of the corresponding E3 and E4 of the vertebrate MiCKs with no intervening intron. E1 is longer and E2 is shorter in the polychaete MiCK gene than the counterpart sarcomeric and ubiquitous genes. The insertion of the intron in C. variopedatus E3 creating the two exons as well as the rearrangement of the intron between E1 and E2 must have occurred prior to or coincident with the duplication event creating the two vertebrate mitochondrial isoforms. Sarcomeric and ubiMiCKs display substantial differences from their invertebrate MiCK counterparts in properties relating to octamer stability and membrane binding. The evolutionary changes in gene topology may be a component of this functional progression.
Pineda
A O
AO
Department of Biological Science and Institute of Molecular Biophysics, Florida State University, 32306-4370, Tallahassee, FL, USA.
Ellington
W R
WR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003402:Creatine Kinase / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005796:Genes / Q000235:genetics*; D007438:Introns; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D011077:Polychaeta / Q000201:enzymology / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004247:DNA; D003402:Creatine Kinase