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Wang, Jue

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Wang, Jue

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2015 - 20162

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Author's Publications: search.filters.isAuthorOfPublication.6acf4a3e-05b6-45f7-b4b8-056664415ece

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    Natural Variation in Preparation for Nutrient Depletion Reveals a Cost–Benefit Tradeoff
    (Public Library of Science, 2015) Wang, Jue; Atolia, Esha; Hua, Bo; Savir, Yonatan; Escalante-Chong, Renan; Springer, Michael
    Maximizing growth and survival in the face of a complex, time-varying environment is a common problem for single-celled organisms in the wild. When offered two different sugars as carbon sources, microorganisms first consume the preferred sugar, then undergo a transient growth delay, the “diauxic lag,” while inducing genes to metabolize the less preferred sugar. This delay is commonly assumed to be an inevitable consequence of selection to maximize use of the preferred sugar. Contrary to this view, we found that many natural isolates of Saccharomyces cerevisiae display short or nonexistent diauxic lags when grown in mixtures of glucose (preferred) and galactose. These strains induce galactose utilization (GAL) genes hours before glucose exhaustion, thereby “preparing” for the transition from glucose to galactose metabolism. The extent of preparation varies across strains, and seems to be determined by the steady-state response of GAL genes to mixtures of glucose and galactose rather than by induction kinetics. Although early GAL gene induction gives strains a competitive advantage once glucose runs out, it comes at a cost while glucose is still present. Costs and benefits correlate with the degree of preparation: strains with higher expression of GAL genes prior to glucose exhaustion experience a larger upfront growth cost but also a shorter diauxic lag. Our results show that classical diauxic growth is only one extreme on a continuum of growth strategies constrained by a cost–benefit tradeoff. This type of continuum is likely to be common in nature, as similar tradeoffs can arise whenever cells evolve to use mixtures of nutrients.
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    Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium
    (Oxford University Press, 2016) Agashe, Deepa; Sane, Mrudula; Phalnikar, Kruttika; Diwan, Gaurav D.; Habibullah, Alefiyah; Martinez-Gomez, Norma Cecilia; Sahasrabuddhe, Vinaya; Polachek, William; Wang, Jue; Chubiz, Lon M.; Marx, Christopher J.
    Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae. These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context.