Ureaplasma Urease Genes have Undergone a Unique Evolutionary Process

Ureaplasma, a member of mycoplasmas, has a unique ATP synthesis system, which is coupled to the urea hydrolysis. Urease catalyzes the hydrolysis of urea into carbon dioxide and ammonia. Phylogenetic analyses of the urease genes indicated that Ureaplasma urease genes were not gained by recent horizontal transfer and have a unique evolutionary process. Ureaplasma unique ATP synthesis system leaded to breakdown of the glycolysis pathway. Some glycolytic genes are absent and some glycolytic genes are evolving under relaxed selection in Ureaplasma. Probably glycolytic genes can be used as an indicator of ATP synthesis system. Thus, the organisms that have incomplete glycolysis pathway or glycolytic genes evolving under relaxed selection would have an ATP synthesis system independently of the glycolysis. Mycoplasmas are widespread in nature as parasites of mammals, reptiles, fishes, arthropods, and plants [1]. During the mycoplasma evolution, gene loss has occurred frequently, resulting in very small genome size [1-3]. The reductive evolution of mycoplasmas is still in progress. The genus Ureaplasma is a member of mycoplasmas, which generates 95% of its ATP using the hydrolysis of urea [4]. Growth of Ureaplasma is dependent on urea [5]. This unique ATP synthesis is not found in the other mycoplasmas. In fact, key enzymes in the glycolytic pathway are absent in Ureaplasma [6]. In addition, some glycolytic genes of Ureaplasma are evolving under relaxed selection [7, 8]. Thus, the glycolysis pathway is collapsing in Ureaplasma. Urea is hydrolyzed into carbon dioxide and ammonia in many organisms. However, it is unique that the urea hydrolysis *Address correspondence to this author at the Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan; E-mail: [email protected] is coupled to ATP synthesis in Ureaplasma [9]. This unique system of Ureaplasma leaded to breakdown of the glycolysis pathway. For example, Ureaplasma does not have any genes encoding glucose-6-phosphate isomerae [10]. It suggests that the glycolysis system had been important for ATP synthesis rather than glucose metabolism at least in Ureaplasma (Fig. 1). Generally the TCA (tricarboxylic acid) cycle is linked to the glycolysis pathway, which has played an important role in ATP synthesis of many organisms and conserved in the course of evolution. On the other hand, the urea hydrolysis is not linked to the glycolysis pathway. Ureaplasma generates ATP through the urea hydrolysis not through the glycolysis. Probably Ureaplasma glycolysis pathway was not able to be broken before the urea hydrolysis was coupled to ATP synthesis. Therefore, after the coupling of the urea hydrolysis and ATP synthesis, dominant ATP synthesis had been changed from through the glycolysis to through the urea hydrolysis during the Ureaplasma evolution (Fig. 1). Fig. (1). Model of change of ATP synthesis system in Ureaplasma. In Ureaplasma, the ATP synthesis through the glycolysis had been changed to that through the urea hydrolysis. The glycolysis pathway was broken after the urea hydrolysis was coupled to ATP synthesis. Urea hydrolysis Glycolysis ATP synthesis Urea hydrolysis Glycolysis ATP synthesis Urea hydrolysis Glycolysis ATP synthesis ATP synthesis PAST SYSTEM