Annexin A11 (ANXA11) gene structure as the progenitor of paralogous annexins and source of orthologous cDNA isoforms

The genomic organization of the annexin A11 gene was determined in mouse an d human to assess its congruity with other family members and to examine th e species variation in alternative splicing patterns. Mouse annexin A11 gen omic clones were characterized by restriction analysis, Southern blotting, and DNA sequencing, and the homologous human gene (HGMW-approved gene symbo l ANXA11) was deciphered from high-throughput genomic sequence with coanaly sis of expressed sequence tags. Exons 6-15 of the tetrad core repeat region differ from annexins A7 and A13 but are spliced identically to other phylo genetic descendents, making annexin A11 the putative primary progenitor of up to nine paralogous human annexins. The 5' regions consist of untranslate d exon 1, followed by an extensive intron 1 comprising almost half the tota l gene length of >40 kb, and additional GC-rich exons 2-5 encoding the prol ine- and glycine-rich amino-terminus, Distinct cDNA isoforms in cow and hum an were determined to be unique to each species and hence of dubious genera l significance for this gene's function. Multiple transcription start sites were revealed by primer extension analysis of the mouse gene, and transfec tion constructs containing the prospective promoter generated transcription al activity comparable to that of the SV40 promoter. Internal repetitive el ements and vicinal gene markers were mapped for the complete human annexin A11 gene sequence to characterize the surrounding genomic environment, (C) 2000 Academic Press.