Transcript Metabolic functions of duplicate genes in Saccharomyces cerevisiae

Metabolic functions of duplicate
genes in Saccharomyces
cerevisiae
Presented by
Tony
Kuepfer et al. 2005
Problem addressed
• What is or are the mechanisms that
lead to the preservation of duplicate
genes in yeast?
Background information
• ~1500 duplicate genes in
S.cerevisiae.
• 105 duplicate gene families with 295
members in S.cerevisiae metabolism.
Proposed mechanisms
1. Back-up function (redundancyrobustness) or specialized function?
2. Gene dosage
3. Differential regulation
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
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Complex medium (YPD)
Glucose
Galactose
Glycerol
Ethanol
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.
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)
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.
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
Discussion
• The 105 yeast
duplicate families
in metabolism do
not have a single
major but rather
an array of
different, often
overlapping
functions.