Spontaneous mutations and the origin and maintenance of quantitative genetic variation
- North Carolina State University, United States
- Washington University in St. Louis, United States
- National Heart Lung and Blood Institute, United States
- Syngenta, United States
Abstract
Mutation and natural selection shape the genetic variation in natural populations. Here, we directly estimated the spontaneous mutation rate by sequencing new Drosophila mutation accumulation lines maintained with minimal natural selection. We inferred strong stabilizing natural selection on quantitative traits because genetic variation among wild-derived inbred lines was much lower than predicted from a neutral model and the mutational effects were much larger than allelic effects of standing polymorphisms. Stabilizing selection could act directly on the traits, or indirectly from pleiotropic effects on fitness. However, our data are not consistent with simple models of mutation-stabilizing selection balance; therefore, further empirical work is needed to assess the balance of evolutionary forces responsible for quantitative genetic variation.
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Spontaneous mutations and the origin and maintenance of quantitative genetic variation
eLife 5:e14625.
https://doi.org/10.7554/eLife.14625
Further reading
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- Genetics and Genomics
- Microbiology and Infectious Disease
Evolution of gene expression frequently drives antibiotic resistance in bacteria. We had previously (Patel and Matange, eLife, 2021) shown that, in Escherichia coli, mutations at the mgrB locus were beneficial under trimethoprim exposure and led to overexpression of dihydrofolate reductase (DHFR), encoded by the folA gene. Here, we show that DHFR levels are further enhanced by spontaneous duplication of a genomic segment encompassing folA and spanning hundreds of kilobases. This duplication was rare in wild-type E. coli. However, its frequency was elevated in a lon-knockout strain, altering the mutational landscape early during trimethoprim adaptation. We then exploit this system to investigate the relationship between trimethoprim pressure and folA copy number. During long-term evolution, folA duplications were frequently reversed. Reversal was slower under antibiotic pressure, first requiring the acquisition of point mutations in DHFR or its promoter. Unexpectedly, despite resistance-conferring point mutations, some populations under high trimethoprim pressure maintained folA duplication to compensate for low abundance DHFR mutants. We find that evolution of gene dosage depends on expression demand, which is generated by antibiotic and exacerbated by proteolysis of drug-resistant mutants of DHFR. We propose a novel role for proteostasis as a determinant of copy number evolution in antibiotic-resistant bacteria.
