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-PCRto 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.
Bibliographical noteFunding Information:
D. Bachtrog and S. Nuzhdin provided some sequence data, and C. Machado provided flies for sequencing. Thanks to J. Merrill and two anonymous reviewers for comments on the manuscript. This research was funded by NIH Grants GM092501 and GM086445. Data were deposited in the Short Read Archive (accession numbers SRA044960.1, SRA044955.2, SRA044956.1); see also http://pseudobase.biology.duke.edu/ .
- Nonsense mutation
- Null mutation
- Premature stop codon