Figure 1

Haploproficiency of a VHR1/NQM1 double heterozygous mutant in late stationary phase. A) Generation of a heterozygous haplotype library. The kanMX4 marker present in the systematic knock-out strains was replaced by the LEU2 in 82 MAT a strains, and these were cross-mated in 96-well plates with the corresponding MAT α collection. After 2 days mating on YPD, double mutants were selected on synthetic media lacking leucine and supplemented with G418. B) The double heterozygous mutant library was combined with the wild type strain BY4743 in a 1:1 ratio and grown in independent duplicates at 30°C for 32 days in synthetic complete media (SC). Viability was monitored every 2nd day by serial dilution plating C) Viability of cells during stationary phase in the double mutant library (green line), wild type within a competitive pool (grey line) or the mutants within the competitive pool (red line). The wild type lost viability in competitive pools at day 26, the double mutants at day 32. The arrow marks time point of clonal selection. These trends in linear scaling are illustrated in Additional file 3, Figure S7, the trends of separate pools in Additional file 4: Figure S8. D) Identification of surviving haplotypes. 78% of genotypes were unique, while the remaining cells were double-heterozygous for Δvhr1 and Δnqm1 E) Gene Ontology (GO) Term analyses of surviving double heterozygous yeast mutants on the basis of their single gene deletion.