Abstract

The Angiotensin-Converting Enzyme (ACE) is crucial for vascular homeostasis in mammals. Three isoforms are present in the human. the somatic ACE (sACE) generates the vasoactive angiotensin II. The testicular isoform (tACE) is required for male fertility. ACE2 was cloned from another gene and displays an antagonistic role. Several ACEs were cloned from insects, despite their lack of a closed circulatory system. Insect isoforms are implied in reproduction and development. No sequence in the C. elegans genome is able to encode a functional enzyme. Nevertheless, an active ACE was characterized in an even more distant organism, the leech, in which the enzyme is mainly expressed within the digestive tract. The presence of ACE is lophotrochozoans raises questions about the appearance and original functions of the enzyme. Besides, the recent availability of genomic data unraveled the putative presence of orthologues in even more distant phyla such as cnidaria, placozoa and even many procaryotes. Moreover, the characterization of an active ACE in a proteobacteria indicates that the ancestor isoform was already functional. Thus, ACE is present from bacteria to mammals and exhibits incredibly conserved molecular, biochemical as well as structural features. The absence of ACE in all eucaryotic bicounts could thus result from a secondary loss. Taken together, these data suggest that ACE appeared early during the course of evolution. Mammalian ACE features could thus be a result of the long evolutive specialization of an ancient protease whose physiological functions remain to be elucidated.