THE MOUSE VCS2 GENE IS A COMPOSITE STRUCTURE WHICH EVOLVED BY GENE FUSION AND ENCODES 5 DISTINCT SALIVARY MESSENGER-RNA SPECIES

Genes of the VCS (variable coding sequence) family are characterized b y an extensive evolutionary divergence in the protein-coding sequence. The VCS family has been characterized by cDNA cloning from submandibu lar glands in the rat, mouse and humans. At the genomic level, the seq uences of two members of this family are known in the rat Rattus norve gicus: the VCSA1 gene, encoding the prohormone-like polypeptide SMR1, and the VCSB1 gene, encoding a salivary Pro-rich polypeptide. No genom ic data were available for the VCS genes of other species. To understa nd the evolution of the VCS gene family better, we have now sequenced 23 kilobases (kb) of the mouse Vcs2 gene. The Vcs2 sequence reveals nu merous genomic reorganizations such as an inversion, insertions of sho rt elements and an unusually high number of long interspersed repeated elements (LINEs), which make up 42% of this region. Interestingly, Vc s2 is composed of three different VCS-like regions. The first of these regions contains all the exons necessary to encode the previously des cribed mouse submandibular gland polypeptide MSG2 alpha. This region a ligns with the entire genomic sequences of rat VCSA1 and VCSB1 genes. The two other regions align with fragments of these rat sequences. The three regions are arrayed in tandem and flanked by LINEs. In particul ar, the third region also contains exons that were found in mRNA speci es from the submandibular gland. In total, we have characterized five mRNAs from mouse submandibular glands which have in common their first exon, and are produced by alternative splicing. Vcs2 is thus a single gene that arose by the fusion of three genes (or pseudogenes) of the VCS multigene family. (C) 1997 Elsevier Science B.V.