scholarly journals Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
María Angélica Bravo Núñez ◽  
Ibrahim M Sabbarini ◽  
Lauren E Eide ◽  
Robert L Unckless ◽  
Sarah E Zanders
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fitness Landscape ◽  
Fitness Costs ◽  
Spore Killing ◽  
Selection Of

Killer meiotic drivers are genetic parasites that destroy ‘sibling’ gametes lacking the driver allele. The fitness costs of drive can lead to selection of unlinked suppressors. This suppression could involve evolutionary tradeoffs that compromise gametogenesis and contribute to infertility. Schizosaccharomyces pombe, an organism containing numerous gamete (spore)-killing wtf drivers, offers a tractable system to test this hypothesis. Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical spores, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness costs of mutations that disrupt meiotic fidelity and, in some circumstances, can even make such mutations beneficial. Moreover, we find that S. pombe isolates vary greatly in their ability to make haploid spores, with some isolates generating up to 46% aneuploid or diploid spores. This work empirically demonstrates the potential for meiotic drivers to shape the evolution of gametogenesis.

scholarly journals Atypical meiosis can be adaptive in outcrossed S. pombe due to wtf meiotic drivers

2020 ◽  
Author(s):  
María Angélica Bravo Núñez ◽  
Ibrahim M. Sabbarini ◽  
Lauren E. Eide ◽  
Robert L. Unckless ◽  
Sarah E. Zanders
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Fitness Landscape ◽  
Fitness Cost ◽  
Fitness Costs ◽  
Diploid Gametes ◽  
Selection Of

AbstractKiller meiotic drivers are genetic parasites that destroy ‘sibling’ gametes lacking the driver allele. The fitness costs of drive can lead to selection of unlinked suppressors. This suppression could involve evolutionary tradeoffs that compromise gametogenesis and contribute to infertility. Schizosaccharomyces pombe, an organism containing numerous gamete-killing wtf drivers, offers a tractable system to test this hypothesis. Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical gametes, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness cost of mutations that disrupt meiotic fidelity and, in some circumstances, can even make such mutations beneficial. Moreover, we find that S. pombe isolates vary greatly in their ability to make haploid gametes, with some isolates generating more than 25% aneuploid or diploid gametes. This work empirically demonstrates the potential for meiotic drivers to shape the evolution of gametogenesis.

scholarly journals Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and drastic amino acid changes in HIV

2016 ◽  
Author(s):  
Kristof Theys ◽  
Alison F. Feder ◽  
Maoz Gelbart ◽  
Marion Hartl ◽  
Adi Stern ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mutation Rate ◽  
Fitness Landscape ◽  
Fitness Costs ◽  
Nonsense Mutations ◽  
Cpg Dinucleotides ◽  
Synonymous Mutations ◽  
The Cost ◽  
Patient Mutation

AbstractHIV has a high mutation rate, which contributes to its ability to evolve quickly. However, we know little about the fitness costs of individual HIV mutationsin vivo, their distribution and the different factors shaping the viral fitness landscape. We calculated the mean frequency of transition mutations at 870 sites of thepolgene in 160 patients, allowing us to determine the cost of these mutations. As expected, we found high costs for non-synonymous and nonsense mutations as compared to synonymous mutations. In addition, we found that non-synonymous mutations that lead to drastic amino acid changes are twice as costly as those that do not and mutations that create new CpG dinucleotides are also twice as costly as those that do not. We also found that G→A and C→T mutations are more costly than A→G mutations. We anticipate that our newin vivofrequency-based approach will provide insights into the fitness landscape and evolvability of not only HIV, but a variety of microbes.Author summaryHIV’s high mutation rate allows it to evolve quickly. However, most mutations probably reduce the virus’ ability to replicate – they are costly to the virus. Until now, the actual cost of mutations is not well understood. We used within-patient mutation frequencies to estimate the cost of 870 HIV mutationsin vivo. As expected, we found high costs for non-synonymous and nonsense mutations. In addition, we found surprisingly high costs for mutations that lead to drastic amino acid changes, mutations that create new CpG sites (possibly because they trigger the host’s immune system), and G→A and C→T mutations. Our results demonstrate the power of analyzing mutant frequencies fromin vivoviral populations to study costs of mutations. A better understanding of fitness costs will help to predict the evolution of HIV.

scholarly journals Adaptive Approaches Towards Better GA Performance in Dynamic Fitness Landscapes

1994 ◽  
Vol 23 (487) ◽  
Author(s):  
Henrik Hautop Lund
Keyword(s):  
Fitness Landscape ◽  
Dynamic Environments ◽  
Mutation Rates ◽  
Landscape Changes ◽  
Correlation Measure ◽  
The Right ◽  
Changes Over Time ◽  
Adaptive Approaches ◽  
Over Time ◽  
Selection Of

We review different techniques for improving GA performance. By analysing the fitness landscape, a correlation measure between parents and offspring can be provided, and we can estimate effectively which genetic operator to use in the GA for a given fitness landscape. The response to selection equation further tells us how well the GA will do, and combining the two approaches gives us a powerful tool to automatically ensure the selection of the right parameter settings for a given problem. In dynamic environments the fitness landscape changes over time, and the evolved systems should be able to adapt to such changes. By introducing evolvable mutation rates and evolvable fitness formulae, we obtain such systems. The systems are shown to be able to adapt to both internal and external constraints and changes.

scholarly journals Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes

2021 ◽  
Vol 118 (18) ◽  
pp. e2026027118
Author(s):  
Satoshi Ikegame ◽  
Takao Hashiguchi ◽  
Chuan-Tien Hung ◽  
Kristina Dobrindt ◽  
Kristen J. Brennand ◽  
...  
Keyword(s):  
Measles Virus ◽  
Fitness Landscape ◽  
Subacute Sclerosing Panencephalitis ◽  
Brain Regions ◽  
Wild Type ◽  
Genomic Context ◽  
Fitness Advantage ◽  
Human Neurons ◽  
Selection Of

Measles virus (MeV) is resurgent and caused >200,000 deaths in 2019. MeV infection can establish a chronic latent infection of the brain that can recrudesce months to years after recovery from the primary infection. Recrudescent MeV leads to fatal subacute sclerosing panencephalitis (SSPE) or measles inclusion body encephalitis (MIBE) as the virus spreads across multiple brain regions. Most clinical isolates of SSPE/MIBE strains show mutations in the fusion (F) gene that result in a hyperfusogenic phenotype in vitro and allow for efficient spread in primary human neurons. Wild-type MeV receptor-binding protein is indispensable for manifesting these mutant F phenotypes, even though neurons lack canonical MeV receptors (CD150/SLAMF1 or nectin-4). How such hyperfusogenic F mutants are selected and whether they confer a fitness advantage for efficient neuronal spread is unresolved. To better understand the fitness landscape that allows for the selection of such hyperfusogenic F mutants, we conducted a screen of ≥3.1 × 105 MeV-F point mutants in their genomic context. We rescued and amplified our genomic MeV-F mutant libraries in BSR-T7 cells under conditions in which MeV-F-T461I (a known SSPE mutant), but not wild-type MeV, can spread. We recovered known SSPE mutants but also characterized at least 15 hyperfusogenic F mutations with an SSPE phenotype. Structural mapping of these mutants onto the prefusion MeV-F trimer confirm and extend our understanding of the F regulatory domains in MeV-F. Our list of hyperfusogenic F mutants is a valuable resource for future studies into MeV neuropathogenesis and the regulation of paramyxovirus F.

scholarly journals Molecular Genetic and Structural Modeling Studies of Staphylococcus aureus RNA Polymerase and the Fitness of Rifampin Resistance Genotypes in Relation to Clinical Prevalence

2006 ◽  
Vol 50 (1) ◽  
pp. 298-309 ◽  
Author(s):  
A. J. O'Neill ◽  
T. Huovinen ◽  
C. W. G. Fishwick ◽  
I. Chopra
Keyword(s):  
Staphylococcus Aureus ◽  
Rna Polymerase ◽  
Molecular Genetic ◽  
Fitness Costs ◽  
Novel Mutations ◽  
Resistant Strains ◽  
Rifampin Resistance ◽  
First Time ◽  
Selection Of

ABSTRACT The adaptive and further evolutionary responses of Staphylococcus aureus to selection pressure with the antibiotic rifampin have not been explored in detail. We now present a detailed analysis of these systems. The use of rifampin for the chemotherapy of infections caused by S. aureus has resulted in the selection of mutants with alterations within the β subunit of the target enzyme, RNA polymerase. Using a new collection of strains, we have identified numerous novel mutations in the β subunits of both clinical and in vitro-derived resistant strains and established that additional, undefined mechanisms contribute to expression of rifampin resistance in clinical isolates of S. aureus. The fitness costs associated with rifampin resistance genotypes were found to have a significant influence on their clinical prevalence, with the most common clinical genotype (H481N, S529L) exhibiting no fitness cost in vitro. Intragenic mutations which compensate for the fitness costs associated with rifampin resistance in clinical strains of S. aureus were identified for the first time. Structural explanations for rifampin resistance and the loss of fitness were obtained by molecular modeling of mutated RNA polymerase enzymes.

Quantitative Selection of Respiratory Deficient Mutants in Yeasts by Triphenyltetrazolium Chloride

1972 ◽  
Vol 27 (3) ◽  
pp. 252-256 ◽  
Author(s):  
V. Bachofen ◽  
R. J. Schweyen ◽  
K. Wolf ◽  
F. Kaudewitz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Inhibition ◽  
Schizosaccharomyces Pombe ◽  
Respiratory Chain ◽  
Mutation Induction ◽  
Terminal Oxidase ◽  
Triphenyltetrazolium Chloride ◽  
Tetrazolium Chloride ◽  
Selection Of ◽  
Respiratory Deficient

Triphenyltetrazolium chloride exhibits a strong growth inhibition in respiratory competent cells but shows only minor effects in respiratory deficient mutants of Saccharomyces cerevisiae and Schizosaccharomyces pombe. Use of this dye thus allows rapid selection of rarely occurring respiratory deficient mutants, showing karyotic as well as extrakaryotic inheritance. Mutation induction by tetrazolium chloride was not observed. The results favour the hypothesis that triphenyltetrazolium chloride interferes with the terminal oxidase of the respiratory chain.

scholarly journals Diverse mating phenotypes impact the spread of wtf meiotic drivers in Schizosaccharomyces pombe

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
José Fabricio López Hernández ◽  
Rachel M Helston ◽  
Jeffrey J Lange ◽  
R Blake Billmyre ◽  
Samantha H Schaffner ◽  
...  
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Cell Density ◽  
Sexual Partners ◽  
Clonal Lineage ◽  
Fitness Costs ◽  
Genetic Elements ◽  
Natural Isolates

Meiotic drivers are genetic elements that break Mendel's law of segregation to be transmitted into more than half of the offspring produced by a heterozygote. The success of a driver relies on outcrossing (mating between individuals from distinct lineages) because drivers gain their advantage in heterozygotes. It is, therefore, curious that Schizosaccharomyces pombe, a species reported to rarely outcross, harbors many meiotic drivers. To address this paradox, we measured mating phenotypes in S. pombe natural isolates. We found that the propensity for cells from distinct clonal lineages to mate varies between natural isolates and can be affected both by cell density and by the available sexual partners. Additionally, we found that the observed levels of preferential mating between cells from the same clonal lineage can slow, but not prevent, the spread of a wtf meiotic driver in the absence of additional fitness costs linked to the driver. These analyses reveal parameters critical to understanding the evolution of S. pombe and help explain the success of meiotic drivers in this species.

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