Structural organization and evolution of the liver isoform gene for bovine cytochrome c oxidase subunit VIIa.

Subunit VIIa of mammalian cytochrome c oxidase is one of three nuclear-encoded subunits that exhibit isoforms, existing predominantly as an H-form in cardiac and skeletal muscle tissues and as an L-form in others. We have isolated and characterized the L-isoform gene (COX7aL). It is 5.4 kb long, consists of four exons, and is located at a CpG island. Sp1 sites and an NRF1 site are located in an approximately 100-bp region immediately upstream of the gene. Comparison of the sequence and organization with the previously described H-isoform gene shows identical intron-exon organizations, with the first intron of both isoform genes splitting the presequence coding region almost identically. These results suggest that the isoform genes arose by duplication from a common ancestor prior to the mammalian radiation and that the ancestor already contained the presequences. In addition, four processed pseudogenes of the L-type have been isolated and characterized, one of which (COX7aLP1) contains no deletions, insertions, or frame-shifts and can encode a precursor protein of 83 amino acids. Construction of a phylogenetic tree employing extant COX7aL cDNA and bovine pseudogene sequences suggests that the expressed bovine gene and COX7aLP1 arose from a gene duplication event 4.6-6.8 Mya.