Olfactory receptor pseudo-pseudogenes

By: James V. Kohl | Published on: October 25, 2016

Olfactory receptor pseudo-pseudogenes

Pseudogenes are generally considered to be non-functional DNA sequences that arise through nonsense or frame-shift mutations of protein-coding genes1. 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, which reflect low selection pressures on loci no longer relevant to the fitness of a species4. Here we report the characterization of a pseudogene in the chemosensory variant ionotropic glutamate receptor repertoire5, 6 of Drosophila sechellia, an insect endemic to the Seychelles that feeds almost exclusively on the ripe fruit of Morinda citrifolia7. This locus, D. sechellia Ir75a, bears a premature termination codon (PTC) that appears to be fixed in the population. However, D. sechellia Ir75a encodes a functional receptor, owing to efficient translational read-through of the PTC. Read-through is detected only in neurons and is independent of the type of termination codon, but depends on the sequence downstream of the PTC. Furthermore, although the intact Drosophila melanogaster Ir75a orthologue detects acetic acid—a chemical cue important for locating fermenting food8, 9 found only at trace levels in Morinda fruit10—D. sechellia Ir75a 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’ could represent a widespread phenomenon.


We suggest that read-through is due to PTC recognition by a near- cognate tRNA that allows insertion of an amino acid instead of translation termination. Although the trans-acting factors regulating read-through are unclear, the neuronal specificity of this process is reminiscent of RNA editing and micro-exon splicing, in which key responsible regulatory proteins are neuronally enriched20,21. We therefore speculate that tissue-specific expression differences in tRNA populations underlie neuron-specific read-through.

My comment: Fixation of amino acid substitutions in organized genomes is nutrient energy-dependent and controlled by the physiology of reproduction.  Odor-tuning does not evolve.
See also: Feedback loops link odor and pheromone signaling with reproduction
My comment: Feedback loops do not evolve
See also: The phylogenetic utility and functional constraint of microRNA flanking sequences
See also: Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses

 …it is obvious that the regulated degradation of proteins must also play a role in sculpting the proteome during homeostatic scaling. Indeed, we observed many proteins in the ubiquitin proteasome pathway that were regulated by scaling (Figure 3C; Table S3).

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The Polycomb repressive system underpins the regulation of developmental gene expression programs during embryogenesis (Fisher and Fisher 2011) and is important in lineage commitment (Chamberlain et al., 2008). We show that transcriptional changes associated with lineage priming in ESC populations correlate with levels of H3K27me3…

My comment: Polycombic ecological adaptation can be linked from energy-dependent changes to the regulation of developmental gene expression programs during embryogenesis via the de novo creation of G protein-coupled receptors during autophagy, which is perturbed by virus-driven energy theft. The virus-driven energy theft is linked to hecatombic evolution of all pathology via the loss of G protein-coupled receptors or loss of their function, but that fact continues to be ignored.

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