Mouse annexin V genomic organization includes an endogenous retrovirus

Mouse annexin V genomic clones were characterized by restriction analysis, Southern blotting and DNA sequencing. The entire gene spans close to 50 kb of the mouse genome and contains 14 exons ranging in size from 31 bp for tr on 2 to 482 bp for exon 13 up to the polyadenylation site. Intron sizes ran ge from 111 bp for intron 1 b to more than 17 kb for intron 2. Noncoding ex on 1 is present in two alternative forms separated by approx. 7.4 kb, and t he two promoters associated with exons la and Ib are quite distinct. The up stream promoter has a TATA box and may direct the limited, tissue-specific expression of mRNA transcripts containing exon 1a. The downstream, TATA-les s promoter has high G + C content, and exon Ib predominates among abundantl y expressed mRNA species. The conservation of certain cis-elements, includi ng Spl, AP2, gamma-IRE and NF-IL6, in orthologous species of annexin V gene s points to their possible role in trans-acting protein factor binding and gene regulation. Primer-extension analysis revealed multiple origins for tr anscription, with principal start sites 100-150 bp upstream of the ATG star t codon in exon 2. Intron 4 was longer than that previously identified in t he orthologous rat gene due to the integration of an apparently complete co py of the murine endogenous retrovirus element, MuERV-L. Phylogenetic analy sis of annexin V from 12 species and the presence of neighbouring loci with paralogous counterparts linked to annexin VI pointed to the common ancestr y of these genes via chromosomal duplication more than 600 million years ag o.