Molecular evolution of nucleoside diphosphate kinase genes: conserved core structures and multiple-layered regulatory regions.

Genomic data regarding the nucleoside diphosphate (NDP) kinase genes have been accumulated from diverged phyla. Comparison of their regulatory sequences have shed light on the multiple facets of gene regulation systems. Phylogenetic studies, including CpG island and intron-mapping, and homologous sequence comparison, have suggested that the regions of the major mammalian genes, the ortholog (rat alpha or nm23-H2) and its paralog (rat beta or nm23-H1), have been constructed by a stepwise gain and loss of alien genes resulting in "multiple-layered" regulatory systems. They contain representative cis-elements for the constitutive, stage/lineage-specific, and early response expression. These elements' binding capacities to nuclear proteins were confirmed by electrophoretic mobility shift assay. Further, these regulatory systems generate heterogeneous mRNA at the 5' untranslated region, which influences their own translation efficiencies. In terms of this process, the transcription system would control another layer of gene expression: posttranscriptional (translational) regulation.