Dataset Information

Investigating Potassium Channels in Budding Yeast: A Genetic Sandbox.

ABSTRACT: Like all species, the model eukaryote Saccharomyces cerevisiae, or Bakers' yeast, concentrates potassium in the cytosol as an electrogenic osmolyte and enzyme cofactor. Yeast are capable of robust growth on a wide variety of potassium concentrations, ranging from 10 µM to 2.5 M, due to the presence of a high-affinity potassium uptake system and a battery of cation exchange transporters. Genetic perturbation of either of these systems retards yeast growth on low or high potassium, respectively. However, these potassium-sensitized yeast are a powerful genetic tool, which has been leveraged for diverse studies. Notably, the potassium-sensitive cells can be transformed with plasmids encoding potassium channels from bacteria, plants, or mammals, and subsequent changes in growth rate have been found to correlate with the activity of the introduced potassium channel. Discoveries arising from the use of this assay over the past three decades have increased our understanding of the structure-function relationships of various potassium channels, the mechanisms underlying the regulation of potassium channel function and trafficking, and the chemical basis of potassium channel modulation. In this article, we provide an overview of the major genetic tools used to study potassium channels in S. cerevisiae, a survey of seminal studies utilizing these tools, and a prospective for the future use of this elegant genetic approach.

SUBMITTER: Mackie TD

PROVIDER: S-EPMC6028241 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Investigating Potassium Channels in Budding Yeast: A Genetic Sandbox.

Mackie Timothy D TD Brodsky Jeffrey L JL

Genetics 20180701 3

Like all species, the model eukaryote <i>Saccharomyces cerevisiae</i>, or Bakers' yeast, concentrates potassium in the cytosol as an electrogenic osmolyte and enzyme cofactor. Yeast are capable of robust growth on a wide variety of potassium concentrations, ranging from 10 µM to 2.5 M, due to the presence of a high-affinity potassium uptake system and a battery of cation exchange transporters. Genetic perturbation of either of these systems retards yeast growth on low or high potassium, respecti ...[more]

PMID: 29967058

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Project description:The frequent dispensability of duplicated genes in budding yeast is heralded as a hallmark of genetic robustness contributed by genetic redundancy. However, theoretical predictions suggest such backup by redundancy is evolutionarily unstable, and the extent of genetic robustness contributed from redundancy remains controversial. It is anticipated that, to achieve mutual buffering, the duplicated paralogs must at least share some functional overlap. However, counter-intuitively, several recent studies reported little functional redundancy between these buffering duplicates. The large yeast genetic interactions released recently allowed us to address these issues on a genome-wide scale. We herein characterized the synthetic genetic interactions for ?500 pairs of yeast duplicated genes originated from either whole-genome duplication (WGD) or small-scale duplication (SSD) events. We established that functional redundancy between duplicates is a pre-requisite and thus is highly predictive of their backup capacity. This observation was particularly pronounced with the use of a newly introduced metric in scoring functional overlap between paralogs on the basis of gene ontology annotations. Even though mutual buffering was observed to be prevalent among duplicated genes, we showed that the observed backup capacity is largely an evolutionarily transient state. The loss of backup capacity generally follows a neutral mode, with the buffering strength decreasing in proportion to divergence time, and the vast majority of the paralogs have already lost their backup capacity. These observations validated previous theoretic predictions about instability of genetic redundancy. However, departing from the general neutral mode, intriguingly, our analysis revealed the presence of natural selection in stabilizing functional overlap between SSD pairs. These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners. Our study revealed the general principles for the long-term retention of genetic redundancy.

Dataset Information

Investigating Potassium Channels in Budding Yeast: A Genetic Sandbox.

Publications

Investigating Potassium Channels in Budding Yeast: A Genetic Sandbox.

Similar Datasets

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