Identification of phylogenetic footprints in primate tumor necrosis factor-α promoters

摘要: The human tumor necrosis factor-α (TNF-α) gene encodes a pleiotropic cytokine that plays critical role in basic immunologic processes. To investigate the TNF-α regulatory region primate lineage, we isolated promoters from representative great apes, Old World monkeys, and New monkeys. We demonstrate there is nonuniform distribution of fixed differences promoter. define “fixed difference” as site not polymorphic humans, but which differs at least one seven sequences examined. Furthermore, identify two promoter single nucleotide polymorphisms are putative ancestral polymorphisms, because each nucleotides was found identical other sequences. Strikingly, largest conserved among species, 69-nt “phylogenetic footprint,” corresponds to forms transcriptionally active nucleoprotein–DNA complex, essential for regulation. By contrast, regions promoter, exhibit high density variable sites, nonessential expression, indicating distinct have been subjected different evolutionary constraints depending on their function. first case dissected by functional analyses can be correlated with polymorphism variability lineages. results suggest patterns divergence likely useful identifying candidate important regulation immune-response genes.