Comparative analysis of the UDP-glycosyltransferase multigene family in insects

UDP-glycosyltransferases (UGT) catalyze the conjugation of a range of diverse small lipophilic compounds with sugars to produce glycosides, playing an important role in the detoxification of xenobiotics and in the regulation of endobiotics in insects. Recent progress in genome sequencing has enabled an assessment of the extent of the UGT multigene family in insects. Here we report over 310 putative UGT genes identified from genomic databases of eight different insect species together with a transcript database from the lepidopteran Helicoverpa armigera. Phylogenetic analysis of the insect UGTs showed Order-specific gene diversification and inter-species conservation of this multigene family. Only one family (UGT50) is found in all insect species surveyed (except the pea aphid) and may be homologous to mammalian UGT8. Three families (UGT31, UGT32, and UGT305) related to Lepidopteran UGTs are unique to baculoviruses. A lepidopteran sub-tree constructed with 40 H. armigera UGTs and 44 Bombyx mori UGTs revealed that lineage-specific expansions of some families in both species appear to be driven by diversification in the N-terminal substrate binding domain, increasing the range of compounds that could be detoxified or regulated by glycosylation. By comparison of the deduced protein sequences, several important domains were predicted, including the N-terminal signal peptide, UGT signature motif, and C-terminal transmembrane domain. Furthermore, several conserved residues putatively involved in sugar donor binding and catalytic mechanism were also identified by comparison with human UGTs. Many UGTs were expressed in fat body, midgut, and Malpighian tubules, consistent with functions in detoxification, and some were expressed in antennae, suggesting a role in pheromone deactivation. Transcript variants derived from alternative splicing, exon skipping, or intron retention produced additional UGT diversity. These findings from this comparative study of two lepidopteran UGTs as well as other insects reveal a diversity comparable to this gene family in vertebrates, plants and fungi and show the magnitude of the task ahead, to determine biochemical function and physiological relevance of each UGT enzyme.

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► UGT is a multigene family important in the detoxification of xenobiotics and the regulation of endobiotics in insects.
► Blast searches of public genome databases and local cDNA libraries retrieved over 310 insect UGT genes from nine species.
► Phylogenetic analyses showed the dynamics of diversification and conservation in the multigene family.
► Transcript diversity of Helicoverpa armigera is generated by alternative splicing events.
► Important structural domains and catalytic residues were predicted by multiple sequence alignments.