Abstract
Recent work has found that many metabolic enzymes have the ability to polymerize in response to metabolic changes or environmental stress. This ability to polymerize is well conserved for the few metabolic enzyme paralogs that have been studied in yeast. Here we describe the first set of paralogs, Asn1p and Asn2p, that have differential assembly behavior. Asn1p and Asn2p both co-assemble into filaments in response to nutrient limitation. However, the ability of Asn2p to form filaments is strictly dependent on the presence of Asn1p. Using mutations that block enzyme activity but have differential effects on Asn1p polymerization, we have found that Asn1p polymers are unlikely to have acquired a moonlighting function. Together these results provide a novel system for understanding the regulation and evolution of metabolic enzyme polymerization.
Highlights
Genome duplication is a source of both evolutionary novelty and genetic robustness
Together these results suggest that the main role of Asn1p polymerization is to regulate enzyme activity and suggest that metabolic enzyme paralogs will be useful tool for understanding the role of enzyme polymerization in vivo
In order to distinguish between these two possibilities, we performed colocalization experiments using a yeast strain where Asn1p was tagged with GFP and Asn2p was tagged with mCherry
Summary
Genome duplication is a source of both evolutionary novelty and genetic robustness. these two possibilities are in tension with each other since paralogs diverge or acquire secondary functions, the ability of one paralog to compensate for the other is decreased. While CTP synthetase forms filaments that are conserved from Escherichia coli to mammals[4,6,7,8], in Caulobacter, the formation of these filaments affects cell shape suggesting they might have an additional cytoskeletal role[6] These findings suggested that the identification of paralogs with differential polymerization behavior would be an ideal route to understand both how metabolic enzymes polymerize as well as determine if a given metabolic filament had acquired an evolutionarily novel function. Inactivating mutations in Asn1p that differentially affect polymerization have no effect on growth in rich media arguing that Asn1p filaments have not acquired a second, “moonlighting” function Together these results suggest that the main role of Asn1p polymerization is to regulate enzyme activity and suggest that metabolic enzyme paralogs will be useful tool for understanding the role of enzyme polymerization in vivo
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