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.