The amino sugar metabolic pathway is an essential pathway that is conserved in all three kingdoms of life. NagA, a highly conserved enzyme, carries out the first committed step in the biosynthetic pathway to amino sugar nucleotides. To better understand the evolution of the gene, we have carried out extensive database searches to identify nagA in genomes across the tree of life. Our results indicate the ancient origins of the gene in the unicellular organisms and its presence and conservation in all lineages including the mammals. However, a lineage specific gene loss appears to have occurred in the plants. The phylogenetic tree indicates significant monophyletic clusters that reflect the general phylogeny at the level of the organisms. Moreover, the phylogenetic relationships of the distinct clusters at the level of the amino acid sequence are also reflected in the gene intron-exon structures. Analysis of the gene order in the NagA cluster indicates that nagA exists in an operon nagE-BACD only in few members of the proteobacteria-γ group confirming that the operon is unstable in the long-term evolution. This ancient gene has also undergone highly purifying selection indicating a conserved functional role in evolution. The sequence analysis provides a basis for the evolution of distinct metal binding properties within prokaryotic sequences. Copyright 2010 ACM.