Multiple divergent mRNAs code for a single human calmodulin.

The isolation of a novel complementary DNA (cDNA) clone coding for human calmodulin (CaM) is reported. Although it encodes a protein indistinguishable from the only known higher vertebrate calmodulin, its nucleotide sequence varies extensively from that of two previously reported human CaM cDNAs (Wawrzynczak and Perham, 1984; SenGupta et al., 1987). Only 82 and 81% identity, respectively, is found between the newly isolated and the two known human mRNAs in their coding regions. No striking homology is present in their noncoding regions. Codon usage in the three CaM mRNAs is also surprisingly divergent. A 2.3-kilobase mRNA corresponding to the newly isolated clone is expressed to varying extents in several human tissues, together with an approximately 0.8-kilobase mRNA species presumably arising from alternative polyadenylation of the same primary transcript. The results indicate that the human genome contains at least three divergent CaM genes that are under selective pressure to encode an identical protein while maintaining maximally divergent nucleotide sequences. Partial characterization of a genomic clone specifying the 3' portion of the newly identified CaM mRNA shows that this gene contains introns at identical positions as the previously characterized bona fide vertebrate CaM genes. Evolutionary implications of the presence of a CaM multigene family are discussed.