A TIGHT CLUSTER OF 5 UNRELATED HUMAN GENES ON CHROMOSOME-16Q22.1

A locus on human chromosome 16q22.1 contains at least five tightly clu stered genes which are unrelated by sequence homology and apparently u nrelated by function. The genes for a putative proteasome subunit (MEC L1), a chymotrypsin-like protease (CTRL), a protein serine kinase (PSK H1), the previously cloned lecithin:cholesterol acyl transferase (LCAT ) and a protein of unknown function are found within 40 kb of genomic DNA. Exons from the former four genes are located within a 12 kb regio n including a CpG island associated with the putative proteasome gene. Three of the genes are widely expressed, whereas the genes for the pr otease and LCAT are highly tissue specific. The distance between the t ranscriptional units of the gene upstream of LCAT and LCAT is only 199 bp. Alternative polyadenylation of the protease transcripts creates a transcription unit which overlaps with the oppositely oriented kinase gene. The selective advantage of this unusual gene clustering may inv olve transcriptional interference(s) and coregulatory events not yet u nderstood. Given the current estimate of about 100 000 genes in the hu man genome, our findings support the notion that genes are not evenly distributed.