THE GENETIC-ORIGIN OF MOUSE ANNEXIN-VIII

Mouse annexin VIII cDNA was characterized by DNA sequencing of express ed sequence tag clones, molecular systematic analysis, and genetic lin kage mapping to investigate its evolutionary origin. Its subfamily ide ntity, divergence pattern, and nucleotide substitution rate were estab lished by comparison with other annexin cDNA and deduced protein seque nces. The known phylogenetic association of annexin VIII in an evoluti onary clade with annexins XI, IV, V, and VIa identified these close ho mologs as potential progenitors or duplication products. Cladistic ana lysis confirmed the base position of annexin XI and its relationship t o annexin TV as a direct duplication product. Although annexin Vm also derived from annexin XI, the evolutionary branching order, gene separ ation times, and mapping results indicated that it was probably a subs equent duplication product of annexin IV about 300 million years ago. Dates were calibrated against the assumed separation time of 75 Mya fo r rodents from other mammals, divergence rates were based on compariso ns of all available annexin species, and relative rate tests implied i ndividually stable gene clocks for most annexins. Linkage mapping of m ouse Anus to the centromeric region of Chromosome (Chr) 14 placed it i n a more distal homology group from previously mapped Anx7 and Anx11. Despite their synteny, the combined proximity and segregation of these three annexins diminished the likelihood that they were mutual gene d uplication products.