A NOVEL FAMILY OF CATHEPSIN L-LIKE (CTSLL) SEQUENCES ON HUMAN-CHROMOSOME 10Q AND RELATED TRANSCRIPTS

We have isolated a human genomic DNA cosmid clone while screening for the cathepsin L gene that, when sequenced, revealed close similarity w ith but significant differences from cDNA sequences that have been rep orted for cathepsin L (CTSL). The clone bears a novel sequence that sh ows 88% identity to the coding regions of the cathepsin L gene and a s imilar exon arrangement. We have called this sequence the ''human cath epsin L-like gene 1'' (CTSLL1). Translating putative exon sequences re veals a single premature stop codon; therefore no functional products are likely to arise from this gene. Fluorescence in situ hybridization (FISH) studies mapped the clone to chromosome 10q. Somatic cell hybri d mapping confirmed the location of CTSLL1 to human chromosome 10 dist inct from the cathepsin L locus (CTSL) on chromosome 9. Furthermore, t he FISH mapping studies show that a family of at least three related s equences exists on chromosome 10q, similar to the pattern of duplicate d glutamate dehydrogenase (GLUD) gene loci reported on 10q. Using PCR and sequencing with genomic DNA samples, we have identified two additi onal novel related sequences (CTSLL2 and CTSLL3), and by PCR analysis of cDNA samples we have identified corresponding transcripts. Comparis on of changes between our CTSLL1 sequence and the cathepsin L gene at mutation insensitive sites suggests that the two sequences arose from a duplication event 40-50 million years ago, and therefore at the time of divergence of early primates. (C) 1994 Academic Press, Inc.