Molecular Evolution of the AMP-forming Acetyl-CoA Synthetase. D. Karan , J. David , P. Capy. Lab Population Genetics Evol, CNRS, Gif sur Yvette, France.

   ADP- and AMP-forming Acetyl-CoA-Synthetase (ACS) are involved in the production of acetate, a major metabolite in numerous organisms. We focus mainly on the second gene, which is relatively well conserved in eubacteria, archeae, and eukaryotes. Among the Drosophilidae family, this gene has been sequenced in several species. We used the sequence by Russell et al (Genbank ac=Z46786) as a reference for the all analyses. The coding regions as well as the introns position of this gene are highly conserved. The intron sequences and lengths seem to be highly variable. For example , the second intron of D. takahashii and D. kikkawai is two to three times longer as compared to the other species. BLAST searches in databases showed 30 protein sequences significantly related to the ACS. Most of these sequences were identified as ACS but three of them, belonging to the mammalian species, were annotated as another gene named: the SA gene, which is involved in the essential hypertension. The ACS and SA genes probably derived from a duplication of an ancestral gene but have acquired different functions. Six conserved regions, probably involved in the enzymatic activity of the ACS protein, were defined across the three domains of life. While the precise function of the conserved regions remains unknown, they are. Among eukaryotes, we found a high variability with respect to the number and the position of introns. A maximum likelihood tree based upon the conserved regions showed that all sequences except the one from B. subtilis, belong to two basic groups: one the SA-like group including sequences from Archaeoglobus fulgidus and Streptomyces coelicolor, and second, the ACS group. The later can be further divided in two parts: a prokaryotic one including eubacteria and an archaebacterium, and an eukaryotic group including two proteobacterial sequences. This is in favor of a mitochondrial origin of eukaryotic sequences as also suggested by the localization of the enzyme.