Trends in Biochemical Sciences, Journal Year: 2022, Volume and Issue: 47(5), P. 403 - 416
Published: April 14, 2022
Language: Английский
Oxford University Press eBooks, Journal Year: 2024, Volume and Issue: unknown
Published: May 7, 2024
Abstract Why and how did life become so diverse? This has been the central question—or more accurately, obsession—in biology. book attempts to provide an answer by providing account of biodiversity evolves in some simplest biological systems, microbial populations evolving laboratory. approach, experimental evolution, allows us watch evolutionary process unfold real time track adaptation diversification both phenotype genotype along way, making it possible observe processes that have remained stubbornly inaccessible research larger, longer-lived organisms. The provides insight into ecology genetics adaptive diversification, repeated origins novelty innovation, coevolutionary patterns diversity through ends with a sketch general theory diversification.
Language: Английский
Citations
4
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 6, 2025
Proteins that selectively bind to a target of interest are foundational components research pipelines, diagnostics, and therapeutics. Current immunization-based, display-based, computational approaches for discovering binders laborious time-consuming - taking months or more, suffer from high false positives necessitating extensive secondary screening, have failure rate, especially disordered proteins other challenging classes. Here we establish Phage-Assisted Non-Continuous Selection Protein Binders (PANCS-binders), an in vivo selection platform links the life cycle M13 phage protein binding though customized proximity-dependent split RNA polymerase biosensors, allowing complete comprehensive high-throughput screening billion-plus member variant libraries with signal-to-noise. We showcase utility PANCS-Binders by multiple each against panel 95 separate therapeutically relevant targets, thereby individually assessing over 10^11 protein-protein interaction pairs, completed two days. These selections yielded large, high-quality datasets hundreds novel binders, which showed can be affinity matured directly used mammalian cells inhibit degrade targets. dramatically accelerates simplifies binder discovery process, democratization will help unlock new creative potential proteome-targeting engineered binder-based biotechnologies.
Language: Английский
Citations
0
Genome Biology and Evolution, Journal Year: 2025, Volume and Issue: 17(2)
Published: Jan. 9, 2025
Ant-eating mammals represent a textbook example of convergent evolution. Among them, anteaters and pangolins exhibit the most extreme phenotypes with complete tooth loss, elongated skulls, protruding tongues, hypertrophied salivary glands producing large amounts saliva. However, comparative genomic analyses have shown that differ in their chitinase acidic gene (CHIA) repertoires, which potentially degrade chitinous exoskeletons ingested ants termites. While southern tamandua (Tamandua tetradactyla) harbors four functional CHIA paralogs (CHIA1-4), Asian (Manis spp.) only one paralog (CHIA5). Here, we performed transcriptomic analysis 33 placental species, including 16 novel transcriptomes from ant-eating species close relatives. Our results suggest play an important role adaptation to insect-based diet, as expression different is observed insectivorous species. Furthermore, convergently evolved express chitinases digestive tracts. In Malayan pangolin, CHIA5 overexpressed all major organs, whereas tamandua, are expressed, at very high levels for CHIA1 CHIA2 pancreas CHIA3 CHIA4 glands, stomach, liver, pancreas. Overall, our demonstrate divergent molecular mechanisms within family underlie diet anteaters. This study highlights historical contingency tinkering chitin enzyme toolkit this classic
Language: Английский
Citations
0
Published: Feb. 24, 2025
The evolution of new gene regulation is an important source evolutionary adaptations and innovations, especially when organisms encounter environments. At its heart the process by which strong DNA binding sites transcription factors (TFs) originate in evolution. Here we study potential Darwinian to create for three Escherichia coli global CRP, Fis, IHF. Using a massively parallel reporter assay, measure each TF ability more than 30,000 regulate expression. We use resulting data map adaptive landscape TF. find that all landscapes are rugged, epistatic, harbor multiple peaks. highest peaks widely scattered throughout landscape, indicating can be achieved very different sites. Landscape ruggedness does not prevent regulation, because 10% evolving populations attain one Adaptive starting from same sequence high peak, some likely reached others. Our experiments show de novo feasible. It also subject blend chance, historical contingency, biases favor paths over
Language: Английский
Citations
0
Published: Feb. 24, 2025
The evolution of new gene regulation is an important source evolutionary adaptations and innovations, especially when organisms encounter environments. At its heart the process by which strong DNA binding sites transcription factors (TFs) originate in evolution. Here we study potential Darwinian to create for three Escherichia coli global CRP, Fis, IHF. Using a massively parallel reporter assay, measure each TF ability more than 30,000 regulate expression. We use resulting data map adaptive landscape TF. find that all landscapes are rugged, epistatic, harbor multiple peaks. highest peaks widely scattered throughout landscape, indicating can be achieved very different sites. Landscape ruggedness does not prevent regulation, because 10% evolving populations attain one Adaptive starting from same sequence high peak, some likely reached others. Our experiments show de novo feasible. It also subject blend chance, historical contingency, biases favor paths over
Language: Английский
Citations
0
Genome Biology and Evolution, Journal Year: 2025, Volume and Issue: 17(4)
Published: April 1, 2025
Abstract In this work, we investigate whether the construction of signaling pathways during evolution follows a deterministic law through study eventual link between age appearance in tree life and position pathway genes involved these pathways. We use 47 human described Kyoto Encyclopedia Genes Genomes orthologs 315 animal species plus yeast taxon, representing 15 large clades. Many appear on two key branches: those last common ancestor Opisthokonta Metazoa Deuterostomia Chordata. look for an upstream A gene that its downstream B partner. observe all interactions partners, only 20.6% corresponding arose simultaneously life, 40.7% being called “backward” (i.e. appearing before A) 38.7% “forward” (A B). For 16 pathways, there is positive correlation rank difference interacting partner proteins pathway: more protein pathway, greater (the correlation, or negative, not significant 30 pathways). sole insulin negative. Moreover, by permutation test, find 14 observed contained larger modules (subset respecting homogeneous pattern) than expected chance alone. Finally, 20 scenario appears to be random, as do validate any our statistical tests (permutation interaction direction module sizes well test rank). Given 14.9% are effects different among conclude no rule establishment herein studied patterns have been obscured subsequent transformations.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: March 2, 2024
Abstract Directed evolution is a powerful method in biological engineering. Current approaches draw on time-invariant selection mechanisms, ideal for evolving steady-state properties such as enzymatic activity or fluorescence intensity. A fundamental problem remains how to continuously evolve dynamic, multi-state, computational functionalities, e.g., on-off kinetics, state-specific activity, stimulus-responsiveness, switching and logic capabilities. These require pressure all of the states protein interest (POI) transitions between them. We realized that optogenetics cell cycle oscillations could be leveraged novel directed paradigm (‘optovolution’) germane this need: designed signaling cascade budding yeast where optogenetic input switches POI off (0) (1) states. In turn, controls Cdk1 cyclin, which re-engineered system essential one stage but poisonous another. Thus, cyclin must oscillate (1-0-1-0…) proliferation. system, can act efficiently dynamics, transient states, input-output relations every cycle. Further, controlling pacemaker, light, directs tunes pressures. Optovolution vivo, continuous, self-selecting, efficient. first evolved two systems, relay 0/1 output: obtained 25 new variants widely used LOV transcription factor El222 were stronger, less leaky, green-and red-responsive. The latter was conjectured impossible domains needed multiplexing lowering phototoxicity. Evolving PhyB-Pif3 we discovered loss YOR1 makes supplementing expensive unstable chromophore phycocyanobilin (PCB) unnecessary. Finally, demonstrate generality by destabilized rtTA factor, performs an AND operation transcriptional doxycycline input. coveted, difficult-to-change functionalities evolvable.
Language: Английский
Citations
3
Current Opinion in Chemical Biology, Journal Year: 2023, Volume and Issue: 76, P. 102375 - 102375
Published: Aug. 3, 2023
Language: Английский
Citations
8
Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)
Published: Oct. 25, 2023
Abstract Any reliable biomarker has to be specific, generalizable, and reproducible across individuals contexts. The exact values of such a must represent similar health states in different at times within the same individual result minimum possible false-positive false-negative rates. application standard cut-off points risk scores populations hinges upon assumption generalizability. Such generalizability, turn, this condition that phenomenon investigated by current statistical methods is ergodic, i.e., its measures converge over time finite limit observations. However, emerging evidence indicates biological processes abound with nonergodicity, threatening Here, we present solution for how make generalizable inferences deriving ergodic descriptions nonergodic phenomena. For aim, proposed capturing origin ergodicity-breaking many processes: cascade dynamics. To assess our hypotheses, embraced challenge identifying biomarkers heart disease stroke, which, despite being leading cause death worldwide decades research, lacks stratification tools. We showed raw R-R interval data common descriptors based on mean variance are non-specific. On other hand, cascade-dynamical descriptors, Hurst exponent encoding linear temporal correlations, multifractal nonlinearity nonlinear interactions scales described rate variability more ergodically were specific. This study inaugurates applying critical concept ergodicity discovering digital disease.
Language: Английский
Citations
8
Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(6), P. 1437 - 1446
Published: April 8, 2023
Abstract Proteins from the BCL-2 family control cell survival and apoptosis in health disease, regulate apoptosis-unrelated cellular processes. BCL-Gonad (BCL-G, also known as BCL2-like 14) is a non-typical protein of its long isoform (BCL-G L ) consists BH2 BH3 domains without BH1 motif. BCL-G predominantly expressed normal testes different organs gastrointestinal tract. The complexity regulatory mechanisms expression post-translational modifications suggests that may play distinct roles types cells disorders. While several genetic alterations BCL2L14 have been reported, gene deletions amplifications prevail, which confirmed by analysis sequencing data for cancer. Although studies validating phenotypic consequences manipulations are limited, role has undermined. Recent using gene-perturbation approaches revealed functions intracellular trafficking, immunomodulation, regulation mucin scaffolding network. These were, however, limited mainly to Therefore, further efforts state-of-the-art methods various required find out more about activities. Deciphering isoform-specific interactome result designing novel therapeutic approaches, activity will be either imitated small-molecule mimetics or inhibited counteract upregulation. This review summarizes two decades research on BCL-G.
Language: Английский
Citations
7