Evolutionary adaptation after crippling cell polarization follows reproducible trajectories

Cells are organized by functional modules, which typically contain components whose removal severely compromises the module's function. Despite their importance, these components are not absolutely conserved between parts of the tree of life, suggesting that cells can evolve to perform the same biological functions with different proteins. We evolved Saccharomyces cerevisiae for 1000 generations without the important polarity gene BEM1. Initially the bem1∆ lineages rapidly increase in fitness and then slowly reach >90% of the fitness of their BEM1 ancestors at the end of the evolution. Sequencing their genomes and monitoring polarization reveals a common evolutionary trajectory, with a fixed sequence of adaptive mutations, each improving cell polarization by inactivating proteins. Our results show that organisms can be evolutionarily robust to physiologically destructive perturbations and suggest that recovery by gene inactivation can lead to rapid divergence in the parts list for cell biologically important functions.

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Comparison and Analysis of Computational Methods for Identifying N6 - methyladenosine Sites in Saccharomyces Cerevisiae

Current Pharmaceutical Design ◽

10.2174/1381612826666201109110703 ◽

2020 ◽

Vol 26 ◽

Author(s):

Pengmian Feng ◽

Lijing Feng ◽

Chaohui Tang

Keyword(s):

Saccharomyces Cerevisiae ◽

Computational Methods ◽

Computational Analysis ◽

Computational Prediction ◽

Experimental Methods ◽

Biological Processes ◽

Biological Functions ◽

Precise Location ◽

Future Directions ◽

The Past

Background and Purpose: N 6 -methyladenosine (m6A) plays critical roles in a broad set of biological processes. Knowledge about the precise location of m6A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m6A, they are still labor intensive and time consuming. As good complements to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m6A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m6A sites, it is necessary to give a comprehensive review and comparison on existing methods. Results: Since researches on m6A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progresses on computational prediction of m6A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m6A sites were presented. Conclusion: Taken together, we anticipate that this review will provide important guides for computational analysis of m 6A modifications.

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Identification of the bud emergence gene BEM4 and its interactions with rho-type GTPases in Saccharomyces cerevisiae.

Molecular and Cellular Biology ◽

10.1128/mcb.16.8.4387 ◽

1996 ◽

Vol 16 (8) ◽

pp. 4387-4395 ◽

Cited By ~ 29

Author(s):

D Mack ◽

K Nishimura ◽

B K Dennehey ◽

T Arbogast ◽

J Parkinson ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Synthetic Lethality ◽

Cell Polarization ◽

Growth Defect ◽

Nucleotide Exchange ◽

Loss Of Function ◽

Multicopy Suppressor ◽

Bud Emergence ◽

Multicopy Suppressors ◽

Multiple Copies

The Rho-type GTPase Cdc42p is required for cell polarization and bud emergence in Saccharomyces cerevisiae. To identify genes whose functions are linked to CDC42, we screened for (i) multicopy suppressors of a Ts- cdc42 mutant, (ii) mutants that require multiple copies of CDC42 for survival, and (iii) mutations that display synthetic lethality with a partial-loss-of-function allele of CDC24, which encodes a guanine nucleotide exchange factor for Cdc42p. In all three screens, we identified a new gene, BEM4. Cells from which BEM4 was deleted were inviable at 37 degrees C. These cells became unbudded, large, and round, consistent with a model in which Bem4p acts together with Cdc42p in polarity establishment and bud emergence. In some strains, the ability of CDC42 to serve as a multicopy suppressor of the Ts- growth defect of deltabem4 cells required co-overexpression of Rho1p, which is an essential Rho-type GTPase necessary for cell wall integrity. This finding suggests that Bem4p also affects Rho1p function. Bem4p displayed two-hybrid interactions with Cdc42p, Rho1p, and two of the three other known yeast Rho-type GTPases, suggesting that Bem4p can interact with multiple Rho-type GTPases. Models for the role of Bem4p include that it serves as a chaperone or modulates the interaction of these GTPases with one or more of their targets or regulators.

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Crystal structure of yeast monothiol glutaredoxin Grx6 in complex with a glutathione-coordinated [2Fe–2S] cluster

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x16013418 ◽

2016 ◽

Vol 72 (10) ◽

pp. 732-737 ◽

Cited By ~ 9

Author(s):

Mohnad Abdalla ◽

Ya-Nan Dai ◽

Chang-Biao Chi ◽

Wang Cheng ◽

Dong-Dong Cao ◽

...

Keyword(s):

Crystal Structure ◽

Saccharomyces Cerevisiae ◽

Sequence Alignment ◽

Multiple Sequence Alignment ◽

Active Site ◽

Binding Pattern ◽

Biological Functions ◽

Structural Comparison ◽

Multiple Sequence ◽

Dimeric Structure

Glutaredoxins (Grxs) constitute a superfamily of proteins that perform diverse biological functions. TheSaccharomyces cerevisiaeglutaredoxin Grx6 not only serves as a glutathione (GSH)-dependent oxidoreductase and as a GSH transferase, but also as an essential [2Fe–2S]-binding protein. Here, the dimeric structure of the C-terminal domain of Grx6 (holo Grx6C), bridged by one [2Fe–2S] cluster coordinated by the active-site Cys136 and two external GSH molecules, is reported. Structural comparison combined with multiple-sequence alignment demonstrated that holo Grx6C is similar to the [2Fe–2S] cluster-incorporated dithiol Grxs, which share a highly conserved [2Fe–2S] cluster-binding pattern and dimeric conformation that is distinct from the previously identified [2Fe–2S] cluster-ligated monothiol Grxs.

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Evolutionary stalling and a limit on the power of natural selection to improve a cellular module

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1921881117 ◽

2020 ◽

Vol 117 (31) ◽

pp. 18582-18590 ◽

Cited By ~ 2

Author(s):

Sandeep Venkataram ◽

Ross Monasky ◽

Shohreh H. Sikaroodi ◽

Sergey Kryazhimskiy ◽

Betul Kacar

Keyword(s):

Escherichia Coli ◽

Natural Selection ◽

Adaptive Evolution ◽

Genetic Load ◽

Performance Theory ◽

Biological Functions ◽

Beneficial Mutations ◽

Translation Machinery ◽

Adaptive Mutations ◽

Organismal Fitness

Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations ofEscherichia coliwith genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.

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Primary sequence and biological functions of a Saccharomyces cerevisiae O6-methylguanine/O4-methylthymine DNA repair methyltransferase gene.

The EMBO Journal ◽

10.1002/j.1460-2075.1991.tb07753.x ◽

1991 ◽

Vol 10 (8) ◽

pp. 2179-2186 ◽

Cited By ~ 45

Author(s):

W. Xiao ◽

B. Derfler ◽

J. Chen ◽

L. Samson

Keyword(s):

Saccharomyces Cerevisiae ◽

Dna Repair ◽

Biological Functions ◽

Primary Sequence ◽

Methyltransferase Gene

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Dynamic Localization and Function of Bni1p at the Sites of Directed Growth in Saccharomyces cerevisiae

Molecular and Cellular Biology ◽

10.1128/mcb.21.3.827-839.2001 ◽

2001 ◽

Vol 21 (3) ◽

pp. 827-839 ◽

Cited By ~ 113

Author(s):

Kumi Ozaki-Kuroda ◽

Yasunori Yamamoto ◽

Hidenori Nohara ◽

Makoto Kinoshita ◽

Takeshi Fujiwara ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Fluorescent Protein ◽

Imaging System ◽

Cell Polarization ◽

Actin Binding ◽

Cortical Actin ◽

Dynamic Localization ◽

Directed Growth ◽

And Function

ABSTRACT Formin homology (FH) proteins are implicated in cell polarization and cytokinesis through actin organization. There are two FH proteins in the yeast Saccharomyces cerevisiae, Bni1p and Bnr1p. Bni1p physically interacts with Rho family small G proteins (Rho1p and Cdc42p), actin, two actin-binding proteins (profilin and Bud6p), and a polarity protein (Spa2p). Here we analyzed the in vivo localization of Bni1p by using a time-lapse imaging system and investigated the regulatory mechanisms of Bni1p localization and function in relation to these interacting proteins. Bni1p fused with green fluorescent protein localized to the sites of cell growth throughout the cell cycle. In a small-budded cell, Bni1p moved along the bud cortex. This dynamic localization of Bni1p coincided with the apparent site of bud growth. Abni1-disrupted cell showed a defect in directed growth to the pre-bud site and to the bud tip (apical growth), causing its abnormally spherical cell shape and thick bud neck. Bni1p localization at the bud tips was absolutely dependent on Cdc42p, largely dependent on Spa2p and actin filaments, and partly dependent on Bud6p, but scarcely dependent on polarized cortical actin patches or Rho1p. These results indicate that Bni1p regulates polarized growth within the bud through its unique and dynamic pattern of localization, dependent on multiple factors, including Cdc42p, Spa2p, Bud6p, and the actin cytoskeleton.

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