“Zombie” genes in the olfactory system

Pseudogenes are widely considered to be non-functional parts of the genome. New work has uncovered the phenomenon of pseudo-pseudogenes in the olfactory receptor repertoires of drosophilids that encode for functional receptor proteins through neuron-specific read-through of premature termination codons.

HFSP Young Investigator Grant holder Richard Benton and colleagues
authored on Tue, 06 December 2016

In the genomes of most organisms, dozens to hundreds of genes are functionally disrupted by mutations. One common class of mutation that creates premature termination codons prevents transcripts from genes being translated into protein. Because such genes cannot encode full-length proteins, they are called pseudogenes. Olfactory receptor gene repertoires contain many such pseudogenes, which may be due to the dynamic evolution of this large gene family. For example, when a species changes ecological niche, the genes that encode receptors detecting odours no longer important for its survival in the new environment can often acquire disruptive mutations to render them non-functional.

Figure: Olfactory receptor repertoires contain many pseudogenes, typically considered as dead sequences. New work has identified several examples of presumed pseudogenes that, surprisingly, encode fully functional odour-detecting receptor proteins. Credit: Sonia Aguera Gonzalez.

During our investigations of the olfactory receptor repertoires in Drosophila sechellia, a close cousin of Drosophila melanogaster that lives in the Seychelles and feeds only on the fruit of the Morinda citrifolia shrub, we made a serendipitous discovery. One of D. sechellia’s olfactory receptor pseudogenes – which we had initially assumed had become non-functional due to the specialised diet of this fly species – encodes a fully active receptor protein, despite the presence of a premature termination codon. We found that this pseudo-pseudogene maintains functionality through a mechanism known as translational read-through, which allows cells to ignore the premature termination codon and produce a full-length protein.  Notably, this process appears to occur only in neurons, and not other cell types, implying the existence of specialised translational machinery in neurons.

We went on to identify other examples of pseudo-pseudogenes in other receptor repertoires and other drosophilid species, which makes us suspect that our observations reflect a broader phenomenon. How many of the presumed pseudogenes, in chemosensory and other gene families, across diverse organisms, will be functional?

Reference

Olfactory receptor pseudo-pseudogenes. Prieto-Godino LL, Rytz R, Bargeton B, Abuin L, Arguello JR, Dal Peraro M and Benton R. Nature (2016) 539(7627):93-97 doi: 10.1038/nature19824.

Pubmed link

Link to Nature article

Benton lab website