Mutations that alleviate stresses imposed during growth on DCM had the potential to dramatically increase fitness, and restricting our evolution experiment to 150 generations predominantly selected these mutations.
This deleterious side-effect will select for compensatory mutations that alleviate the fitness trade-off in the lactose environment [ 37, 52- 55].
Our results demonstrate the usefulness of whole genome approaches at detecting major determinants of resistance as well as compensatory mutations that alleviate the fitness cost associated with resistance.
The vib-1 mutant was first identified in a search for mutations that alleviate heterokaryon incompatibility (HI) in N. crassa (Xiang and Glass 2002).
Further investigations into the rate and fitness values of compensatory mutations that alleviate the costs of resistance will help us to better understand both the emergence and management of antibiotic resistance in clinical settings.
In this study, we propose a novel method to detect mutation clusters that alleviates all three drawbacks.
We found that the selection of LNZ resistance is accompanied by the acquisition of resistance determinants that confer a fitness cost and of compensatory mutations that partially alleviates the growth defect of the resistant strains.
A protein or metabolite known to be toxic is expressed in yeast, and deletion mutations that improve (alleviating) or exacerbate (aggravating) the growth inhibitory phenotype of a protein or metabolite known to be toxic identify genes that may illuminate these human disorders.
Moreover, it has been demonstrated that a mutation in the R1 subunit of RNR cdc22-D57NN) thalleviatestes allosteric feedback inhibition resulted in highly elevated dNTP pools that were further increased by deletion of the SPD1 gene.
Compensatory mutation: A second-site mutation that occurs after a mutation that confers resistance, which lessens or alleviates the fitness costs associated with resistance.
