Nematode nuclear receptors as integrators of sensory information

More than 20 years ago, the sequencing of the genome of the nematode Caenorhabditis elegans uncovered a still unparalleled abundance of C4-zinc finger orphan nuclear hormone receptors, encoded by 267 different nhr genes.^1,2 Only less than 20 of them are conserved throughout the animal kingdom; all the remaining genes are the results of an expansion of the HNF4-subtype of nuclear receptors.^3,4 Strikingly, even though most of the receptors contain predicted ligand binding domains, no ligand has since been identified for any of the non-conserved, C. elegans-expanded nhr genes. Based on an analysis of more than 100 nematode genome sequences, as well as the mining of recently established nervous system-wide gene expression patterns, we propose here that nhr family expansion is a manifestation of adaptation of free-living nematodes to complex sensory environments and that NHR proteins may function as sensory receptors for external or internal sensory cues to modulate the animal's sensory responses to environmental cues as well as its internal metabolic state.