Metabolic functions of duplicate genes Metabolic functions of duplicate genes in in Saccharomyces cerevisiaeSaccharomyces cerevisiae

Presented byPresented by

TonyTony

Kuepfer et al. 2005

Problem addressedProblem addressed• What is or are the mechanisms that

lead to the preservation of duplicate genes in yeast?

Background informationBackground information• ~1500 duplicate genes in S.cerevisiae. • 105 duplicate gene families with 295 me

mbers in S.cerevisiae metabolism.

Proposed mechanismsProposed mechanisms1. Back-up function (redundancy-

robustness) or specialized function?2. Gene dosage3. Differential regulation

Methods & ModelMethods & 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 m

utants on 5 conditions– Complex medium (YPD)– Glucose– Galactose– Glycerol– Ethanol

Results for mechanism #1Results 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.

Results for mechanism #1Results 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)

Results for mechanism #2Results for mechanism #2• Do duplicate genes catalyze reactions with hig

h fluxes?– Only 30 of 105 duplicate families are localized in

high flux reactions. • High flux is defined as 5% of higher of the substrate upt

ake rate.– In several cases, a single major isoform is essenti

al.– Finally, only 19 of all duplicate families (105) are c

ategorized to exhibit a potential dosage function.

Results for mechanism #3Results for mechanism #3• Are duplicate genes regulated differenti

ally?– At least 18 of the 105 duplicate gene famili

es 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

DiscussionDiscussion

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