Olfactory receptor pseudo-pseudogenes

Pseudogenes are generally considered to be non-functional DNA sequences that arise from protein-coding genes through nonsense or frame-shift mutations1. Although certain pseudogene-derived RNAs have regulatory roles2, and some pseudogene fragments are translated3, no clear functions for pseudogene-derived proteins are known. Olfactory receptor families contain many pseudogenes, reflecting low selection pressures to maintain receptors that are either functionally redundant or detect odours no longer relevant for a species’ fitness4. Here we have characterised a pseudogene in the chemosensory variant ionotropic glutamate receptor (IR) repertoire5,6 of Drosophila sechellia, an insect endemic to the Seychelles that feeds only on ripe fruit of Morinda citrifolia7. This locus, DsecIr75a, bears a premature termination codon (PTC) that appears to be fixed in the population. Unexpectedly, DsecIr75a encodes a functional receptor, due to efficient translational readthrough of the PTC. Readthrough occurs only in neurons, and is independent of the type of termination codon but dependent upon the sequence downstream of the PTC. Furthermore, while the intact D. melanogaster IR75a orthologue detects acetic acid – a chemical cue important for this species to locate fermenting food8,9 but at trace levels in Morinda fruit10 – DsecIR75a has evolved distinct odour-tuning properties, through amino acid changes in its ligand-binding domain. We identify functional PTC-containing loci within different olfactory receptor repertoires and species, suggesting that such “pseudo-pseudogenes” represent a widespread phenomenon.