1. Metabolic functions of duplicate genes in Saccharomyces cerevisiae Presented by Tony Kuepfer et al. 2005

2. Problem addressed What is or are the mechanisms that lead to the preservation of duplicate genes in yeast?

3. Background information ~1500 duplicate genes in S.cerevisiae. 105 duplicate gene families with 295 members in S.cerevisiae metabolism.

4. Proposed mechanisms 1.Back-up function (redundancy- robustness) or specialized function? 2.Gene dosage 3.Differential regulation

5. Methods & Model iLL672 –Modified from iFF708 –672 genes, 636 metabolites, and 1038 reactions –Predictive capability for single knockouts 96% - 98% for viable 68% - 80% for lethal –Useful in duplicate knockouts (no duplicate knockout library) 3360 plate growth experiments of the 672 single-gene deletion mutants on 5 conditions –Complex medium (YPD) –Glucose –Galactose –Glycerol –Ethanol

6. Results for mechanism #1 Are duplicate genes associated with essential reactions? –Number of lethal single knockouts / number of active genes in the wild type = 63% - 71% –Number of lethal duplicate knockouts / number of active duplicate genes in the wild type = 53% - 74% –Conclusion: Essential reactions are not more likely to be encoded by duplicate genes than by singleton genes.

7. Results for mechanism #1 Do duplicate genes have back-up function? –52 essential duplicate families 32 are experimentally viable when a single gene member is knocked out. (back-up function) 2 exhibit back-up function under only two and three conditions In the remaining 18 essential families, a single member is essential for growth. (specialized function)

8. Results for mechanism #2 Do duplicate genes catalyze reactions with high fluxes? –Only 30 of 105 duplicate families are localized in high flux reactions. High flux is defined as 5% of higher of the substrate uptake rate. –In several cases, a single major isoform is essential. –Finally, only 19 of all duplicate families (105) are categorized to exhibit a potential dosage function.

9. Results for mechanism #3 Are duplicate genes regulated differentially? –At least 18 of the 105 duplicate gene families have potential role in differential regulation of pathways. Located at the beginning or end of linearly coupled reaction sets –Two reactions are coupled if a non-zero flux for R1 implies a non-zero flux for R2 and vice versa. Very little overlap in promoter motifs

10. Discussion The 105 yeast duplicate families in metabolism do not have a single major but rather an array of different, often overlapping functions.