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J. Biol. Chem., Vol. 263, Issue 32, 17055-17062, Nov, 1988
R Fischer, M Koller, M Flura, S Mathews, MA Strehler-Page, J Krebs, JT Penniston, E Carafoli and EE Strehler
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.
Multiple divergent mRNAs code for a single human calmodulin
Laboratory for Biochemistry, Swiss Federal Institute of Technology, Zurich.
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