A common origin for nifV and leuA genes

The enzymes -isopropyl malate (-IPM) synthase (EC 4.1.3.12) and homocytrate (HC) synthase (EC 4.1.3.21) catalyze very similar condensation reactions. -IPM synthase, encoded by leuA, is responsible for the condensation reaction between acetyl coenzyme A and -ketoisovalerate, and represents the first enzyme of the leucine biosynthetic pathway in both bacteria and fungi. HC synthase, encoded by nifV, catalyses the condensation reaction between Acetyl-CoA and -ketoglutarate. In prokaryotes the product of this reaction (homocytrate) is involved in nitrogen fixation, whereas in fungi is involved in lysine biosynthetic pathway. Homology between -IPM synthase from Salmonella typhimurim and Saccharomyces cerevisiae and the product of the nifV gene from Azotobacter chroococcum, Azotobacter vinelandii, and Klebsiella pneumoniae was already observed. Recently the sequence similarity between ORF 1298 of S. cerevisiae and nifV of A. vinelandii led to the identification of LYS20, the major gene encoding HC synthase in S. cerevisiae. The availability of complete sequenced archaeal, bacterial and eukaryal (S. cerevisiae) genomes enabled a detailed comparative analysis of the leuA and nifV gene products. This analysis confirmed the high degree of sequence similarity between the two proteins, and suggested a common ancestry by paralogous gene duplication and subsequent evolutionary divergence. The presence of multiple copies of these genes in several microorganisms belonging to the three cell domains suggested that the ancestral gene, or one of its copies, underwent additional paralogous duplication events, leading to the formation of paralogous gene families. Moreover the presence of leuA and nifV in organisms belonging to the three cell domains also suggested that at least one copy of each leuA and nifV was present in the genome of LUCA (Last Universal Common Ancestor), supporting the idea of an early origin of nitrogen fixation