Cyclooxygenase (COX) has been cloned from the phyla Cnidaria, Mollusca, Arthropoda, and Chordata of the animal kingdom. Many organisms have multiple COX isoforms that have arisen from gene duplication. It is not well understood why there are multiple COX isoforms in the same organism, or when duplication of the COX gene occurred. Here, we summarize the current knowledge of the evolutionary history of COX in the animal kingdom and discuss the reasons why the multiple COX system has been retained so widely. The phylogenetic analysis suggests that all COX genes in animals may descend from a common ancestor and that the duplication of an ancestral COX gene might occur within each lineage after the divergence of the animal. In most instances, the expressions of multiple COX isoforms are separately regulated and these isoforms play different and important pathophysiological roles in each organism. This may be the reason why multiple COX isoforms are widely retained.
