STRUCTURE OF THE HUMAN CALM1 CALMODULIN GENE AND IDENTIFICATION OF 2 CALM1-RELATED PSEUDOGENES CALM1P1 AND CALM1P2

The human CALM1 calmodulin gene has been isolated and characterized. T he gene contains six exons spread over about 10 kb of genomic DNA. The exon-intron structure is identical to that of the human CALM3 and of the rat CALM1 and CALM3 genes. A cluster of transcription-start sites was identified 200 bp upstream of the ATG translation-start codon, and several putative regulatory elements were found in the 5' flanking re gion as well as in intron 1. Sequence comparison with the rat CALM1 ge ne revealed significant similarities in the promoter regions of the tw o genes and an even more striking degree of identity (70%) in the avai lable intron 1 sequences. A short CAG trinucleotide repeat region was identified in the 5' untranslated region of the human CALM1 gene; this sequence is not conserved in the rat counterpart. Expression of the C ALM1 gene was detected in all human tissues tested, although at varyin g levels. A 1.7-kb mRNA was uniformly present at comparable levels, wh ereas a 4.2-kb mRNA species was particularly abundant in brain and ske letal muscle. Clones for two different CALM1-related pseudogenes CALM1 P1 and CALM1P2 were also isolated and characterized. Both pseudogenes are intronless and non-functional as judged from the presence of mutat ions abolishing the open reading frame. Genomic Southern analysis indi cates that the human CALM1 gene/pseudogene subfamily comprises at leas t three but probably no more than four members. The entire family cons ists of three bona fide CALM genes, at least one expressed calmodulin- like CALML gene as well as at least five pseudogenes.