Epistasis and evolution: recent advances and an outlook for prediction

BMC Biology, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 24, 2023

Abstract As organisms evolve, the effects of mutations change as a result epistatic interactions with other accumulated along line descent. This can lead to shifts in adaptability or robustness that ultimately shape subsequent evolution. Here, we review recent advances measuring, modeling, and predicting epistasis evolutionary trajectories, both microbial cells single proteins. We focus on simple patterns global emerge this data, which be predicted by small number variables. The emergence these offers promise for efforts model predict

Language: Английский

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Tetrahymena meiosis: Simple yet ingenious

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(7), P. e1009627 - e1009627

Published: July 15, 2021

The presence of meiosis, which is a conserved component sexual reproduction, across organisms from all eukaryotic kingdoms, strongly argues that sex primordial feature eukaryotes. However, extant meiotic structures and processes can vary considerably between organisms. ciliated protist Tetrahymena thermophila , diverged animals, plants, fungi early in evolution, provides one example rather unconventional meiosis. has simpler meiosis compared with most other organisms: It lacks both synaptonemal complex (SC) specialized machinery for chromosome cohesion reduced capacity to regulate recombination. Despite this, it also features several unique mechanisms, including elongation the nucleus twice cell length promote homologous pairing prevent recombination sister chromatids. Comparison programs higher multicellular may reveal how evolved proto-meiosis.

Language: Английский

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Evolutionary Repair Experiments as a Window to the Molecular Diversity of Life

Current Biology, Journal Year: 2020, Volume and Issue: 30(10), P. R565 - R574

Published: May 1, 2020

Language: Английский

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The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stress

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Feb. 11, 2020

Many biological features are conserved and thus considered to be resistant evolutionary change. While rapid genetic adaptation following the removal of genes has been observed, we often lack a mechanistic understanding how happens. We used budding yeast, Saccharomyces cerevisiae, investigate plasticity chromosome metabolism, network modules. experimentally evolved cells constitutively experiencing DNA replication stress caused by absence Ctf4, protein that coordinates enzymatic activities at forks. Parallel populations adapted stress, over 1000 generations, acquiring multiple, concerted mutations. These mutations altered two metabolism modules, sister chromatid cohesion, inactivated third, damage checkpoint. The selected define functionally reproducible trajectory. suggest implications for genome evolution in natural cancer.All plants, animals fungi share common ancestor, though they have become very distinct billions years, all essential machinery needed grow divide. At heart this is complex interaction proteins involved replication, process duplicating material every time cell divides. needs done with great care, error rates as small one mistake billion. Otherwise, can accumulate genome, causing problems long-term survival. Despite overall principles remaining same, underlying mechanisms vary across different organisms. Given precision complexity replicating DNA, it was not clear had differences. Fumasoni Murray set out answer forcing strain yeast evolve removing gene an important, but essential, component replication. were still able reproduce, hampered mutation. studied after reproduced thousand giving enough acquire new would allow compensate initial defects. In eight separate samples, made many same changes order overcome original segregation third feature normally protect against accumulation damaged DNA. findings show pathways controlled, laboratory environment quickly processes damaged. behavior mutated mimicked cancer cells, which struggling adapt their machinery. Studying follows perturbations could help researchers better deal challenges treatment development antibiotic resistance bacteria, well leading deeper both biology.

Language: Английский

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Mediator recruits the cohesin loader Scc2 to RNA Pol II-transcribed genes and promotes sister chromatid cohesion

Current Biology, Journal Year: 2022, Volume and Issue: 32(13), P. 2884 - 2896.e6

Published: June 1, 2022

The ring-like cohesin complex plays an essential role in chromosome segregation, organization, and double-strand break repair through its ability to bring two DNA double helices together. Scc2 (NIPBL humans) together with Scc4 functions as the loader of onto chromosomes. Chromatin adapters such RSC facilitate localization Scc2-Scc4 loader. Here, we identify a broad range Scc2-chromatin protein interactions that are evolutionarily conserved reveal for one complex, Mediator, recruitment We identified budding yeast Med14, subunit Mediator high copy suppressor poor growth mutant strains. Physical genetic between functionally substantiated direct cohesion assays. Depletion Med14 results defective sister chromatid decreased binding at RNA Pol II-transcribed genes. Previous work has suggested Nipbl, connect enhancers promoters active mammalian Our studies suggest fundamental

Language: Английский

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ATM signaling modulates cohesin behavior in meiotic prophase and proliferating cells

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(4), P. 436 - 450

Published: March 6, 2023

Cohesins are ancient and ubiquitous regulators of chromosome architecture function, but their diverse roles regulation remain poorly understood. During meiosis, chromosomes reorganized as linear arrays chromatin loops around a cohesin axis. This unique organization underlies homolog pairing, synapsis, double-stranded break induction, recombination. We report that axis assembly in Caenorhabditis elegans is promoted by DNA-damage response (DDR) kinases activated at meiotic entry, even the absence DNA breaks. Downregulation cohesin-destabilizing factor WAPL-1 ATM-1 promotes association cohesins containing kleisins COH-3 COH-4. ECO-1 PDS-5 also contribute to stabilizing axis-associated cohesins. Further, our data suggest cohesin-enriched domains promote repair mammalian cells depend on WAPL inhibition ATM. Thus, DDR Wapl seem play conserved prophase proliferating cells.

Language: Английский

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Expanded roles for the MutL family of DNA mismatch repair proteins

Yeast, Journal Year: 2020, Volume and Issue: 38(1), P. 39 - 53

Published: July 11, 2020

The MutL family of DNA mismatch repair proteins plays a critical role in excising and repairing misincorporation errors during replication. In many eukaryotes, members this have evolved to modulate resolve recombination intermediates into crossovers meiosis. these organisms, such functions promote the accurate segregation chromosomes meiosis I division. What alterations occurred homolog (MLH) that enabled them acquire new roles? review, we present evidence yeast Mlh1-Mlh3 Mlh1-Mlh2 complexes novel enzymatic nonenzymatic activities protein-protein interactions are for their meiotic functions. Curiously, even with changes, retain backup accessory roles vegetative growth.

Language: Английский

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Mutational robustness changes during long-term adaptation in laboratory budding yeast populations

eLife, Journal Year: 2022, Volume and Issue: 11

Published: July 26, 2022

As an adapting population traverses the fitness landscape, its local neighborhood (i.e., collection of effects single-step mutations) can change shape because interactions with mutations acquired during evolution. These changes to distribution affect both rate adaptation and accumulation deleterious mutations. However, while numerous models landscapes have been proposed in literature, empirical data on how this evolution remains limited. In study, we directly measure landscape laboratory adaptation. Using a barcode-based mutagenesis system, 91 specific gene disruption genetic backgrounds spanning 8000-10,000 generations two constant environments. We find that mean decreases one environment, indicating reduction mutational robustness, but does not other. show these distribution-level patterns result from differences relative frequency certain epistasis at level individual mutations, including fitness-correlated idiosyncratic epistasis.

Language: Английский

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Experimental evolution for cell biology

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(11), P. 903 - 912

Published: May 15, 2023

Evolutionary cell biology explores the origins, principles, and core functions of cellular features regulatory networks through lens evolution. This emerging field relies heavily on comparative experiments genomic analyses that focus exclusively extant diversity historical events, providing limited opportunities for experimental validation. In this opinion article, we explore potential laboratory evolution to augment evolutionary toolbox, drawing inspiration from recent studies combine with biological assays. Primarily focusing approaches single cells, provide a generalizable template adapting protocols fresh insight into long-standing questions in biology.

Language: Английский

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Evolutionary Divergence in DNA Damage Responses among Fungi

mBio, Journal Year: 2021, Volume and Issue: 12(2)

Published: March 16, 2021

Cell cycle checkpoints and DNA repair pathways contribute to maintaining genome integrity are thought be evolutionarily ancient broadly conserved. For example, in the yeast Saccharomyces cerevisiae humans, damage induces activation of a checkpoint effector kinase, Rad53p (human homolog Chk2), promote cell arrest transcription genes. However, recent studies have revealed variation response networks some fungi. Shor et al. (mBio 11:e03044-20, 2020, https://doi.org/10.1128/mBio.03044-20) demonstrate that comparison S. cerevisiae, fungal pathogen Candida glabrata has reduced damage. Consequently, downstream targets maintenance, such as polymerases, transcriptionally downregulated C. Downregulation maintenance genes likely contributes higher rates mitotic failure death This other findings highlight evolutionary diversity eukaryotic responses.

Language: Английский

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