Effects of premature termination codon polymorphisms in the Drosophila pseudoobscura subclade.

Premature termination codon (PTC) mutations can have dramatic effects--both adaptive and deleterious--on gene expression and function. Here, we examine the number and selective effects of PTC mutations within the Drosophila pseudoobscura subclade using 18 resequenced genomes aligned to the reference genome. We located and characterized 1,679 PTC mutations in 605 genes across each of these genomes relative to the D. pseudoobscura reference genome, and use RT-PCR to confirm transcription of a subset of these genes containing PTC mutations. We confirm previous findings that genes containing PTC mutations are less selectively constrained and less broadly expressed than non-PTC-containing genes, suggesting that the most of these mutations are at least mildly deleterious. Further, we find highly significant codon usage bias in regions downstream of the PTC in 38 of these PTC-containing genes, suggesting that some of these PTC mutations--if not alternatively spliced out of the transcript--have neutral effects. Ultimately, these analyzes support the view that the PTC mutations are mostly detrimental, but are nonetheless common enough in genomes that a subset could be effectively neutral.