Plasticity of genetic interactions in metabolic networks of yeast

Harrison, Richard J.; Papp, Balázs; Pál, Csaba; Oliver, Stephen G.; Delneri, Daniela

doi:10.1073/pnas.0607153104

Cited by 188 publications

(209 citation statements)

References 51 publications

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“…Support to the generation of neutral genotypic diversity after gene duplication comes from the classic belief that after duplication gene copies suffer relaxed selective constraints that allow one or both copies tolerating many-fold more mutations than otherwise, a fact with extensive experimental and theoretical support [2,86,87]. This phenomenon is more obvious when analyzing genomes populated with duplicates originated by whole-genome duplication, in which younger duplicates still preserve signatures of their larger tolerance to mutations than older duplicates [79,84,88,89]. The fact that expansion of certain protein families is concomitant with the emergence of morphological diversity sparks the possibility that gene duplication is linked to robustness and evolvability.…”

Section: Evolution By Gene Duplication: Robustness To Mutational Insultsmentioning

confidence: 93%

Survival and innovation: The role of mutational robustness in evolution

Fares

2015

Biochimie

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a b s t r a c tBiological systems are resistant to perturbations caused by the environment and by the intrinsic noise of the system. Robustness to mutations is a particular aspect of robustness in which the phenotype is resistant to genotypic variation. Mutational robustness has been linked to the ability of the system to generate heritable genetic variation (a property known as evolvability). It is known that greater robustness leads to increased evolvability. Therefore, mechanisms that increase mutational robustness fuel evolvability. Two such mechanisms, molecular chaperones and gene duplication, have been credited with enormous importance in generating functional diversity through the increase of system's robustness to mutational insults. However, the way in which such mechanisms regulate robustness remains largely uncharacterized. In this review, I provide evidence in support of the role of molecular chaperones and gene duplication in innovation. Specifically, I present evidence that these mechanisms regulate robustness allowing unstable systems to survive long periods of time, and thus they provide opportunity for other mutations to compensate the destabilizing effects of functionally innovative mutations. The findings reported in this study set new questions with regards to the synergy between robustness mechanisms and how this synergy can alter the adaptive landscape of proteins. The ideas proposed in this article set the ground for future research in the understanding of the role of robustness in evolution.

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Section: Evolution By Gene Duplication: Robustness To Mutational Insultsmentioning

confidence: 93%

Survival and innovation: The role of mutational robustness in evolution

Fares

2015

Biochimie

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“…Complex phenotypes have been shown to be fairly insensitive to random genomic manipulations in many systems (17,18). This mutational robustness is often the result of congruently evolved pathways within the genetic network that buffer the effects of individual mutations (18). One possibility is that the sasA mutations are uncovering a cryptic mechanism with functional redundancy by relaxing its suppression.…”

Section: Discussionmentioning

confidence: 99%

“…It is surprising that the cell can compensate for its loss to both the input and output pathways with a single-nucleotide mutation in the sasA gene. Complex phenotypes have been shown to be fairly insensitive to random genomic manipulations in many systems (17,18). This mutational robustness is often the result of congruently evolved pathways within the genetic network that buffer the effects of individual mutations (18).…”

Section: Discussionmentioning

confidence: 99%

Single mutations in sasA enable a simpler Δ cikA gene network architecture with equivalent circadian properties

Shultzaberger

Boyd

Katsuki

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The circadian input kinase of the cyanobacterium Synechococcus elongatus PCC 7942 (CikA) is important both for synchronizing circadian rhythms with external environmental cycles and for transferring temporal information between the oscillator and the global transcriptional regulator RpaA (regulator of phycobilisome-associated A). KOs of cikA result in one of the most severely altered but still rhythmic circadian phenotypes observed. We chemically mutagenized a cikA-null S. elongatus strain and screened for second-site suppressor mutations that could restore normal circadian rhythms. We identified two independent mutations in the Synechococcus adaptive sensor A (sasA) gene that produce nearly WT rhythms of gene expression, likely because they compensate for the loss of CikA on the temporal phosphorylation of RpaA. Additionally, these mutations restore the ability to reset the clock after a short dark pulse through an output-independent pathway, suggesting that SasA can influence entrainment through direct interactions with KaiC, a property previously unattributed to it. These experiments question the evolutionary advantage of integrating CikA into the cyanobacterial clock, challenge the conventional construct of separable input and output pathways, and show how easily the cell can adapt to restore phenotype in a severely compromised genetic network.gene network | cyanobacteria | evolution S econd-site suppressor mutagenesis screens have been useful in untangling the genetic components and pathways that underlie complex cellular phenotypes (1). By understanding how mutations in one gene can compensate for changes in another, we can infer how those genes interact with each other and with their encompassing genetic network. We used this approach to better understand the genetic determination of circadian rhythms in the cyanobacterium Synechococcus elongatus PCC 7942. Because the core clock genes in this species exist as single copies, suppressing mutations are not buffered by paralogs, making S. elongatus ideal for this type of mutagenic assay. Approximately 15 genes have been identified that influence the circadian phenotype to various degrees, the most important of which are the kai genes: kaiA, kaiB, and kaiC. In cyanobacteria, time is kept through the central oscillator protein KaiC, whose phosphorylation state, conformation, and ATPase activity, which are mediated by interactions with KaiA and KaiB, cycle within a 24-h period (2-4). The temporal phosphorylation of KaiC can be reconstituted in vitro by simply combining the three Kai proteins and ATP, suggesting that time is kept primarily through a posttranslational mechanism (5). Although the Kai oscillator functions relatively robustly in isolation, additional proteins are necessary to synchronize the oscillations with the environment (entrainment) through the detection of cellular and environmental cues (input pathway) and to transfer temporal information from the oscillator to circadian-dependent transcriptional regulators (output pathway). One of these prot...

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“…The phenomenon is evident most clearly on a whole-genome scale 15,16 , where recent gene duplicates in various eukaryotes tolerate 10-fold more amino acid changes than old duplicates 15 . Eventually, the accumulating changes may cause duplicates to diversify their function, and sometimes quite rapidly 11,17,18 .…”

Section: Gene Duplications Cause Robustnessmentioning

confidence: 99%

Gene duplications, robustness and evolutionary innovations

Wagner

2008

BioEssays

118

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Gene duplications, robustness and evolutionary innovations Gene duplications, robustness and evolutionary innovations AbstractMutational robustness facilitates evolutionary innovations. Gene duplications are unique kinds of mutations, in that they generally increase such robustness. The frequent association of gene duplications in regulatory networks with evolutionary innovation is thus a special case of a general mechanism linking innovation to robustness. The potential power of this mechanism to promote evolutionary innovations on large time scales is illustrated here with several examples. These include the role of gene duplications in the vertebrate radiation, flowering plant evolution and heart development, which encompass some of the most striking innovations in the evolution of life. Gene duplications, robustness, and evolutionary innovationsAndreas Wagner AbstractMutational robustness facilitates evolutionary innovations in biological systems. Gene duplications are unique kinds of mutations, in that they generally increase such robustness. The frequent association of gene duplications in regulatory networks with evolutionary innovation thus exemplifies a general mechanism linking innovation to robustness. I illustrate the potential power of this mechanism on large time scales with the role of gene duplications in the vertebrate radiation, flowering plant evolution, and heart development, which encompass some of the most striking innovations in the evolution of life. Mutational robustnessMutational robustness is a biological's system ability to withstand mutations. Such robustness exists on multiple levels of biological organization. A case in point are random mutagenesis experiments of various proteins. They suggest that only a small fraction of mutations affect protein function adversely. For instance, a study of the bacteriophage T4 lysozyme generated more than 2000 random amino acid changes in the protein. Only 16% of them affected lysozyme function 1 . Other examples come from regulatory gene networks, such as the molecular network specifying fruit fly segments. Such networks may tolerate much quantitative variation in interactions among network genes 2-5 . Examples at the highest level of organization include macroscopic traits. Even substantial genetic variation -ultimately caused by mutations -may leave such traits unchanged. Take the vulva of the nematode worms Caenorhabditis elegans and Pristionchus pacificus 6 . These organisms shared a common ancestor 200-300 million years ago. Their vulvae are very similar, yet the genetic and cellular networks producing them have diverged greatly. For example, whereas in C. elegans one specific cell -the anchor cell -induces vulva development, multiple gonadal cells are responsible for this induction in P. pacificus 7 . Similarly, the same key signaling molecules, such as Wnt, may play a positive role in the network for vulval induction in C. elegans, but a negative role in P. pacificus 8,9 . In sum, mutational robustness is everywhere, from proteins to or...

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Plasticity of genetic interactions in metabolic networks of yeast

Cited by 188 publications

References 51 publications

Survival and innovation: The role of mutational robustness in evolution

Survival and innovation: The role of mutational robustness in evolution

Single mutations in sasA enable a simpler Δ cikA gene network architecture with equivalent circadian properties

Gene duplications, robustness and evolutionary innovations

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