26 papers · ranked by Valyu relevance
Haoran Yin, Anna V. Kononova, Thomas Bäck, Niki van Stein
Evolution of Algorithms Authors: ['Haoran Yin' 'Anna V. Kononova' 'Thomas Bäck' 'Niki van Stein'] Abstract. The integration of Large Language Models (LLMs) with evolutionary computation (EC) has introduced a promising paradigm for automating the design of metaheuristic algorithms. However, existing frameworks, such as…
Aysima Hacisuleyman, Deniz Yuret, Burak Erman
The oncogenic G12D mutation in KRAS is a major driver of cancer progression, yet the complete mechanism by which this mutation alters protein dynamics and function remains incompletely understood. Here, we investigate how the G12D mutation alters KRAS’s conformational landscape and residue-residue interactions using…
Yijia Zhou, Funan He, Weilin Pu, Xun Gu + 2 more
DNA methylation is a dynamic epigenetic modification found in most eukaryotic genomes. It is known to lead to a high CpG to TpG mutation rate. However, the relationship between the methylation dynamics in germline development and the germline mutation rate remains unexplored. In this study, we used whole genome…
Chao Hou, Haiqing Zhao, Yufeng Shen
Structural dynamics are fundamental to protein functions and mutation effects. Current protein deep learning models are predominantly trained on sequence and/or static structure data, which often fail to capture the dynamic nature of proteins directly. To address this, we introduce SeqDance and ESMDance, two protein…
Authors not listed
Free energy calculations have become invaluable in protein design, offering a powerful means to rapidly and accurately screen potential variants. Here, we provide a step-by-step protocol that combines molecular dynamics simulations with non-equilibrium alchemical free energy methods to tackle open questions in protein…
Siobain Duffy
The high mutation rate of RNA viruses is credited with their evolvability and virulence. This Primer, however, discusses recent evidence that this is, in part, a byproduct of selection for faster genomic replication.
Wen Wei, Wei-Chin Ho, Megan G. Behringer, Samuel F. Miller + 2 more
'George Bcharah' 'Michael Lynch'] Ecological and demographic factors can significantly shape the evolution of microbial populations both directly and indirectly, as when changes in the effective population size affect the efficiency of natural selection on the mutation rate. However, it remains unclear how rapidly the…
Johann Bauer, Mark Broom, Eduardo Alonso
The multi-population replicator dynamics (RD) can be considered a dynamic approach to the study of multi-player games, where it was shown to be related to Cross' learning, as well as of systems of coevolving populations. However, not all of its equilibria are Nash equilibria (NE) of the underlying game, and neither…
Authors not listed
SIMPLE SUMMARY TP53 gene is really important for keeping our cells healthy. It does this by fixing damaged DNA, managing cell growth, and telling cells to die if they're too damaged to repair. But when TP53 has mutations,these defenses stop working, and cells start growing out of control. One of the big problems in…
Authors not listed
The persistent failure to drug mutant forms of key oncogenes—such as TP53, KRAS, and MYC—is largely due to their lack of stable, visible binding pockets in crystal structures. These proteins are frequently labeled “undruggable,” not because they cannot be modulated, but because their ligandable sites are hidden…
Larry Bull
This short paper presents an abstract, tunable model of genomic structural change within the cell lifecycle and explores its use with simulated evolution. A well-known Boolean model of genetic regulatory networks is extended to include changes in node connectivity based upon the current cell state, e.g., via…
Kabir Husain, Vedant Sachdeva, Riccardo Ravasio, Michele Peruzzo + 3 more
The traits that affect evolvability are subject to indirect selection, as these traits affect the course of evolution over many generations rather than the direct replicative fitness of an individual. However, the evolution of evolvability-determining traits is often difficult to study because putative evolvability…
Paco Majic, Malvika Srivastava, Justin Crocker
Mutation rates drive the pace and potential of evolutionary change. However, to better understand the evolutionary implications of mutation rates, there is a need to uncover the causes of their diversfification. In multicellular organisms, all mutations first arise in a single cell in a developmental context. Whether a…
Adi Livnat
together Authors: ['Adi Livnat'] Background The modern evolutionary synthesis leaves unresolved some of the most fundamental, long-standing questions in evolutionary biology: What is the role of sex in evolution? How does complex adaptation evolve? How can selection operate effectively on genetic interactions? More…
Dario A. Leon, Augusto González
Taking into account an evolutionary model of mutations in term of Levy flights that was previously constructed, we designed an algorithm to reproduce the evolutionary dynamics of the Long-Term Evolution Experiment (LTEE) with E. Coli bacteria. The algorithm enables us to simulate mutations under natural selection…
Authors not listed
RNA droplets assembled from co-transcriptionally folded nanostructures have recently emerged as a promising platform for constructing protocells and minimal synthetic cell models. In these systems, a custom-designed DNA template encodes an RNA nanostar, which is produced by transcription and self-assembles into…
James S. Horton, Tiffany B. Taylor
Genetic mutation, which provides the raw material for evolutionary adaptation, is largely a stochastic force. However, there is ample evidence showing that mutations can also exhibit strong biases, with some mutation types and certain genomic positions mutating more often than others. It is becoming increasingly clear…
Gabriela Lobinska, Yitzhak Pilpel, Yoav Ram
Mutation rate plays an important role in adaptive evolution due to its effect on the rate of appearance of both beneficial and deleterious mutations and is therefore subject to second-order selection. The mutation rate varies between and within species and populations, increases under some stresses, and can be modified…
Authors not listed
TP53 has long been deemed “undruggable,” particularly in its mutant forms, due to the lack of stable, targetable pockets. In this study, I report the discovery of a cryptic binding pocket induced by the C238Y mutation in TP53—absent in the wild-type protein and formed through local loop flexibility. Using flexible…
Authors not listed
The glycine receptor (GlyR) is a pentameric ligand-gated ion channel that plays important physiological roles in the nervous system. Its malfunction is related to neurological disorders including startle disease (hyperekplexia), which is characterized by exaggerated startle responses to sudden unexpected stimuli, such…
Krzysztof Gogolewski, Michał Startek, Anna Gambin, Arnaud Le Rouzic
Although transposable elements were discovered in the middle of the 20th century and are known as one of the main genome components, their impact on genome evolution has not been fully elucidated yet. However, it was so far shown that mutations induced by transposition events can lead to significant genetic disorders…
Sarah Eberle, Djeneba Dezoumbe, Rhegan McGregor, Shane Kinzer + 3 more
'Whitney Raver' 'Sarah Schaack' 'Leigh C. Latta IV'] Understanding the context-dependence of spontaneous mutations is crucial to predicting evolutionary trajectories. In this experiment, the impact of genetic background and trait-type on mutational susceptibility was investigated. Mutant and non-mutant lines of six…
Ziyue Gao, Minyoung J. Wyman, Guy Sella, Molly Przeworski
Mutations can arise from the chance misincorporation of nucleotides during DNA replication or from DNA lesions that are not repaired correctly. We introduce a model that relates the source of mutations to their accumulation with cell divisions, providing a framework for understanding how mutation rates depend on sex…
Gemma Fisher, Marina Corbella, Magnus S. Alphey, John Nicholson + 3 more
ATP phosphoribosyltransferase catalyses the first step of histidine biosynthesis and is controlled via a complex allosteric mechanism where the regulatory protein HisZ enhances catalysis by the catalytic protein HisGS while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisGS…
Scott Alexander Lujan, Thomas A. Kunkel, Bernard S. Lopez, Ivan Matic
'Ivan Matic'] We describe the contribution of DNA mismatch repair (MMR) to the stability of the eukaryotic nuclear genome as determined by whole-genome sequencing. To date, wild-type nuclear genome mutation rates are known for over 40 eukaryotic species, while measurements in mismatch repair-defective organisms are…
Emma L. Berdan, Alexandre Blanckaert, Tanja Slotte, Alexander Suh + 2 more
'Anja M. Westram' 'Inês Fragata'] - 1. Department of Ecology, Environment and Plant Sciences, Science for Life Laboratory, Stockholm University, Stockholm, Sweden SE-10691 - 2. Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706 - 3. School of Biological Sciences Organisms and the Environment…