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 tron 2 to 482 bp for exon 13 up to the polyadenylation site. Intron sizes range from 111 bp for intron 1 b to more than 17 kb for intron 2. Noncoding exon 1 is present in two alternative forms separated by approx. 7.4 kb, and the two promoters associated with exons la and Ib are quite distinct. The upstream promoter has a TATA box and may direct the limited, tissue-specific expression of mRNA transcripts containing exon 1a. The downstream, TATA-less promoter has high G + C content, and exon Ib predominates among abundantly expressed mRNA species. The conservation of certain cis-elements, including Spl, AP2, gamma-IRE and NF-IL6, in orthologous species of annexin V genes points to their possible role in trans-acting protein factor binding and gene regulation. Primer-extension analysis revealed multiple origins for transcription, with principal start sites 100-150 bp upstream of the ATG start codon in exon 2. Intron 4 was longer than that previously identified in the orthologous rat gene due to the integration of an apparently complete copy of the murine endogenous retrovirus element, MuERV-L. Phylogenetic analysis of annexin V from 12 species and the presence of neighbouring loci with paralogous counterparts linked to annexin VI pointed to the common ancestry of these genes via chromosomal duplication more than 600 million years ago.