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PubMed2026

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Humans↗

PubMed2025

Contrasting rhizosphere nitrogen dynamics in Andropogoneae grasses.

Nitrogen (N) fertilization in crop production significantly impacts ecosystems, often disrupting natural plant-microbe-soil interactions and causing environmental pollution. This study tested the hypothesis that diverse species adapting independently to various environments might exhibit a wide range of rhizosphere nutrient management strategies, and some of them may be conducive to an efficient N economy for crops. We analyzed the N cycle in the rhizospheres of 36 Andropogoneae grass species related to maize and sorghum and observed significant phylogenetic variation among their impacts on N availability and losses. All three annual species examined, including sorghum and maize, function as N 'Conservationists', reducing soil nitrification potential and conserving NH4 +. In contrast, seven of the assayed perennial species enhance nitrification and leaching ('Leachers'). Four other species exhibit similar nitrification stimulation effects but limited NO3 - losses ('Nitrate Keepers'). We complemented the controlled phenotypic evaluation with an evolutionary-ecological analysis of the same species. We identified several soil characteristics associated with the phylogenetic variation in rhizosphere N dynamics across grasses and highlighted the crucial roles of a few transporter genes in soil N management and utilization. In addition to the ecological and genetic insights, these findings offer valuable guidelines for future maize breeding efforts to enhance agricultural N efficiency and sustainability.

Rhizosphere↗

PubMed2002

Forgiveness: origins, dynamics, psychopathology, and technical relevance.

This paper integrates a diverse and scattered literature to describe the psychodynamic underpinnings of granting and seeking forgiveness. The evolutionary foundations and the developmental substrate of these capacities are elucidated. An individual who fails to make certain intrapsychic achievements may be vulnerable to psychopathological development, as is evident in those who cannot forgive or forgive too readily, constantly or never seek others' forgiveness, cannot accept forgiveness, or show an imbalance between their capacities to forgive themselves and to forgive others. The relevance of various developmental and phenomenological concepts to psychoanalytic technique, including the patient's need to forgive and to be forgiven, is also discussed.

Anger↗

PubMed1991

Classification of cell receptors.

This manuscript constitutes a first attempt to categorize the cell receptors. Based on evolutionary and biological characteristics, it is possible to classify ligand-receptor units into original families. Certain dynamic patterns that could not be classified previously lead us towards the ligand-receptor unit. Biological information is transformed at the receptor by cellular transduction and effector pathways. The dynamic code is compared with the genetic code. The dynamic code controls the biological information patterns necessary for the integral function and structure of cells, tissue, organs, and organisms. The genetic code controls the assembly and molecular structure of proteins. The original families can be assigned certain original functions. A coevolution of ligand-receptor and dynamic code is revealed. For the time being the most useful approach to receptor classification would seem to be based on the organization of the molecular and protein structure of receptors. Two classes of receptor can be described: receptors for cyclic hydrophobic compounds and membrane receptors. Until we know of the families of single membrane-spanning receptors, fourfold membrane-spanning receptors, sevenfold membrane-spanning receptors, fourfold membrane-spanning receptors. For the sevenfold membrane-spanning receptor the identity of conformation and dynamics of biological function has been established. Light and peptide ligands are used as examples. A systems theory for information transduction at receptors is introduced which can also describe the processes of sensitivity modulation.

Amino Acid Sequence↗

PubMed1989

Saltatory transitions are a naturally occurring property of evolving systems.

On the basis of paleological evidence, it has been suggested that biological evolution need not necessarily be characterized by gradual change. Rather, evolutionary history may display saltatory periods of rapid speciation alternating with periods of relative quiescence, the whole dynamic being called punctuated equilibria. The empirical evidence that has been presented in support of this hypothesis has been the object of a vigorous dispute. Mathematical investigations of complex models of biological evolution that contain random elements have demonstrated that these systems can display saltatory behavior. In this paper we address a more abstract question: can saltations occur in the evolution of very simple, deterministic mathematical systems that function in a constant environment? The answer appears to be yes. Saltations appear as a natural dynamical behavior in the evolution of simplistic information processing networks. We stress that these networks do not constitute a model of biological evolution. However, the appearance of saltations in such simple systems suggests that their appearance in a process as complex as biological evolution is not surprising.

Animals↗

PubMed2006

5S rDNA variation and its phylogenetic inference in the genus Leporinus (Characiformes: Anostomidae).

5S rDNA sequences have proven to be valuable as genetic markers to distinguish closely related species and also in the understanding of the dynamic of repetitive sequences in the genomes. In the aim to contribute to the knowledge of the evolutionary history of Leporinus (Anostomidae) and also to contribute to the understanding of the 5S rDNA sequences organization in the fish genome, analyses of 5S rDNA sequences were conducted in seven species of this genus. The 5S rRNA gene sequence was highly conserved among Leporinus species, whereas NTS exhibit high levels of variations related to insertions, deletions, microrepeats, and base substitutions. The phylogenetic analysis of the 5S rDNA sequences clustered the species into two clades that are in agreement with cytogenetic and morphological data.

Animals↗

PubMed1989

DNA, mutations and aging.

Genetic instability is widely thought to be involved in the process of aging. Evolutionary theory suggests that aging may well result from stochastic damage to DNA. However, studies of the dynamics of accumulation of simple somatic mutations have shown that such a mechanism cannot readily account for experimental observations. A more complex mutational theory of aging is emerging which allows for interaction between mutations, for damage to epigenetic controls on gene expression, and for interaction of (epi)genetic changes with other possible molecular events contributing to aging.

Aging↗

PubMed1985

Meso and racemic organisms and the transition to asymmetry.

In this paper we analyse extensive but previously unappreciated and scattered data on anomalous enzyme modulation by metabolite enantiomers for enzymes in the principle metabolic cycles and develop a coherent theory for their derivation from reciprocally coupled antipodal metabolisms in antecedent meso and racemic organisms. Structures for such chirally symmetric organisms are outlined, as is the gradual decoupling of their integrated antipodal metabolisms upon an evolutionary progression from meso organism to racemic organism to racemate of organisms. The driving forces and the dynamics for a transition to asymmetry are developed.

Animals↗

PubMed2001

An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy.

Evolutionary games have been applied as simple mathematical models of populations where interactions between individuals control the dynamics. Recently, it has been proposed to use this type of model to describe the evolution of tumour cell populations with interactions between cells. We extent the analysis to allow for synergistic effects between cells. A mathematical model of a tumour cell population is presented in which population-level synergy is assumed to originate through the interaction of triplets of cells. A threshold of two cooperating cells is assumed to be required to produce a proliferative advantage. The mathematical behaviour of this model is explored. Even this simple synergism (minor clustering effect) is sufficient to generate qualitatively different cell-population dynamics from the models published previously. The most notable feature of the model is the existence of an unstable internal equilibrium separating two stable equilibria. Thus, cells of a malignant phenotype can exist in a stable polymorphism, but may be driven to extinction by relatively modest perturbations of their relative frequency. The proposed model has some features that may be of interest to biological interpretations of gene therapy. Two prototypical strategies for gene therapy are suggested, both of them leading to extinction of the malignant phenotype: one approach would be to reduce the relative proportion of the cooperating malignant cell type below a certain critical value. Another approach would be to increase the critical threshold value without reducing the relative frequency of cells of the malignant phenotype.

Algorithms↗

PubMed2005

Life history biology of early land plants: deciphering the gametophyte phase.

The ca. 400-million-year-old Rhynie chert biota represents a benchmark for studies of early terrestrial ecosystems. The exquisite preservation of the organisms documents an ancient biodiversity that also includes various levels of biological interaction. Absent from the picture until recently has been detailed information about the development of the gametophyte phase and the alternation of generations of the macroplants in this ecosystem. Here, we trace the development of the gametophyte phase of Aglaophyton, an early land plant with an unusual complement of structural and morphological characters. Mature gametophytes consist of a fleshy protocorm attached to the substrate by basal rhizoids; arising from the upper surface are one to several upright gametangiophores bearing multiple gametangia. Stomata are present on the upper surface of the protocorm and gametangiophore, and endomycorrhizal fungi extend throughout the gametophyte. Gametophytes are unisexual, producing either antheridiophores or archegoniophores. There is no evidence that gametophytes later become hermaphroditic. The sexual dimorphism of the Rhynie chert gametophytes is inconsistent with theoretical ideas about the haploid phase of early land plants. The gametophyte phase of early land plants can now be considered within an ecological and evolutionary framework that, in turn, can be used to develop hypotheses about some aspects of the population dynamics and growth of these early land plants.

Biodiversity↗

PubMed1991

Parasites and sexual selection: a macroevolutionary perspective.

The Hamilton-Zuk hypothesis postulates a causal link between parasitism and the evolution of epigamic traits by intersexual selection. Oversimplified assumptions about basic parasite biology, ambiguous formulation of the hypothesis, and poor communication between ethologists and parasitologists have hampered its testing. The hypothesis is supported at the microevolutionary level if females show significant preference for lightly or uninfected males, if intensity of infection reflects host resistance to parasites that depress host fitness by causing disease, and if intensity of infection is related to the degree of epigamic development. It must be shown that particular parasites cause disease, that the host population is polymorphic for resistance to infection by those species, and that female hosts are capable of distinguishing male hosts with low parasite loads due to heritable aspects of host resistance from males that are uninfected due to chance. The macroevolutionary prediction of the hypothesis, that species displaying strongly developed epigamic characters should host "more parasites" than species with weakly developed epigamic traits, contradicts the microevolutionary dynamic of the hypothesis, and is too ambiguous. We propose a macroevolutionary prediction based on understanding the evolutionary origin of epigamic traits and the evolutionary origin of each host-parasite association. Associations originating in the ancestor in which the epigamic trait appeared corroborate the hypothesis most strongly; those originating prior to the evolution of the epigamic trait corroborate it weakly; those beginning after the origin of the epigamic trait could not have been involved in the origin and spread of the epigamic trait.

Animals↗

PubMed2004

Lost in time, lonely, and single: reproductive asynchrony and the Allee effect.

Identifying linkages between life-history traits and small population processes is essential to effective multispecies conservation. Reproductive asynchrony, which occurs when individuals are reproductively active for only a portion of the population-level breeding period, may provide one such link. Traditionally, reproductive asynchrony has been considered from evolutionary perspectives as an advantageous bet-hedging strategy in temporally unpredictable environments. Here, we explore the dynamic consequences of reproductive asynchrony as a density-dependent life-history trait. To examine how asynchrony affects population growth rate and extinction risk, we used a general model of reproductive timing to quantify the temporal overlap of opposite-sex individuals and to simulate population dynamics over a range of initial densities and empirical estimates of reproductive asynchrony. We also considered how protandry, a sexually selected life-history strategy that often accompanies asynchrony, modulates the population-level effects of reproductive asynchrony. We found that asynchrony decreases the number of males a female overlaps with, decreases the average probability of mating per male/female pair that does overlap, and leaves some females completely isolated in time. This loss of reproductive potential, which is exacerbated by protandry, reduces population growth rate at low density and can lead to extinction via an Allee effect. Thus reproductive asynchrony and protandry, both of which can be evolutionarily advantageous at higher population densities, may prove detrimental when population density declines.

Animals↗

PubMed2002

Exact mapping of prokaryotic gene starts.

It is known that while the programs used to find genes in prokaryotic genomes reliably map protein-coding regions, they often fail in the exact determination of gene starts. This problem is further aggravated by sequencing errors, most notably insertions and deletions leading to frame-shifts. Therefore, the exact mapping of gene starts and identification of frame-shifts are important problems of the computer-assisted functional analysis of newly sequenced genomes. Here we review methods of gene recognition and describe a new algorithm for correction of gene starts and identification of frame-shifts in prokaryotic genomes. The algorithm is based on the comparison of nucleotide and protein sequences of homologous genes from related organisms, using the assumption that the rate of evolutionary changes in protein-coding regions is lower than that in non-coding regions. A dynamic programming algorithm is used to align protein sequences obtained by formal translation of genomic nucleotide sequences. The possibility of frame-shifts is taken into account. The algorithm was tested on several groups of related organisms: gamma-proteobacteria, the Bacillus/Clostridium group, and three Pyrococcus genomes. The testing demonstrated that, dependent or a genome, 1-10 per cent of genes have incorrect starts or contain frame-shifts. The algorithm is implemented in the program package Orthologator-GeneCorrector.

Algorithms↗

PubMed2025

Bayesian inference of fitness landscapes via tree-structured branching processes.

MOTIVATION: The complex dynamics of cancer evolution, driven by mutation and selection, underlies the molecular heterogeneity observed in tumors. The evolutionary histories of tumors of different patients can be encoded as mutation trees and reconstructed in high resolution from single-cell sequencing data, offering crucial insights for studying fitness effects of and epistasis among mutations. Existing models, however, either fail to separate mutation and selection or neglect the evolutionary histories encoded by the tumor phylogenetic trees. RESULTS: We introduce FiTree, a tree-structured multi-type branching process model with epistatic fitness parameterization and a Bayesian inference scheme to learn fitness landscapes from single-cell tumor mutation trees. Through simulations, we demonstrate that FiTree outperforms state-of-the-art methods in inferring the fitness landscape underlying tumor evolution. Applying FiTree to a single-cell acute myeloid leukemia dataset, we identify epistatic fitness effects consistent with known biological findings and quantify uncertainty in predicting future mutational events. The new model unifies probabilistic graphical models of cancer progression with population genetics, offering a principled framework for understanding tumor evolution and informing therapeutic strategies. AVAILABILITY AND IMPLEMENTATION: The Python package FiTree and the analysis workflows are available at https://github.com/cbg-ethz/FiTree.

Bayes Theorem↗

PubMed2025

First chromosome-level genome assembly of the colonial chordate model Botryllus schlosseri (Tunicata).

BACKGROUND: Botryllus schlosseri (Tunicata) is a colonial, laboratory model tunicate recognized for its remarkable developmental diversity, its regenerative abilities, and its peculiar genetically determined allorecognition system governed by a polymorphic locus controlling chimerism and cell parasitism. RESULTS: We report the first chromosome-level genome assembly of B. schlosseri subclade A1. By integrating long and short reads with Hi-C scaffolding, we produced both a phased diploid genome assembly and a conventional collapsed consensus sequence of 533 Mb. Of this total length, 96% belonged to 16 chromosome-scale scaffolds, with a BUSCO completeness score of 91.4%. We then compared our assembly with other high-quality tunicate genomes, revealing some synteny conservation but also extensive genomic rearrangements and a general loss of colinearity. CONCLUSIONS: The chromosome-level resolution of this assembly enhances our understanding of genome organization in colonial modular organisms. Comparative analyses highlight the dynamic nature of tunicate genomes, with conserved macrosynteny yet extensive microsyntenic rearrangements and scrambling, underscoring their rapid evolutionary trajectory. This high-quality genome assembly provides a valuable resource for exploring the unique biological features of colonial chordates, including their exceptional regenerative abilities and complex allorecognition system.

Animals↗

PubMed2001

The evolution of cooperative breeding through group augmentation.

Some individuals (helpers) in cooperatively breeding species provide alloparental care and often suppress their own reproduction. Kin selection is clearly an important explanation for such behaviour, but a possible alternative is group augmentation where individuals survive or reproduce better in large groups and where it therefore pays to recruit new members to the group. The evolutionary stability of group augmentation is currently disputed. We model evolutionarily stable helping strategies by following the dynamics of social groups with varying degrees of subordinate help. We also distinguish between passive augmentation, where a group member benefits from the mere presence of others, and active augmentation, where their presence as such is neutral or harmful, but where helping to recruit new group members may still be beneficial if they in turn actively provide help for the current reproductives ('delayed reciprocity'). The results show that group augmentation (either passive or active) can be evolutionarily stable and explain costly helping by non-reproductive subordinates, either alone or leading to elevated help levels when acting in concert with kin selection. Group augmentation can thus potentially explain the weak relationships between relatedness and helping behaviour that are observed in some cooperatively breeding species. In some cases, the superior mutualistic performance of cooperatively behaving groups can generate an incentive to stay and help which is strong enough to make ecological constraints unnecessary for explaining the stability of cooperatively breeding groups.

Animals↗

PubMed2004

Evolution of developmental canalization in networks of competing boolean nodes.

Developmental canalization, which leads to a reduction in the variation of phenotype expression relative to the complexity of the genome, has long been thought to be an important property of evolving biological systems. We demonstrate that a highly canalized state develops in the process of self-organization recently discovered in N-K Boolean networks that evolve based on a competition between the nodes. The model provides a simplified description of the evolution of genetic regulatory networks in developmental systems. The mechanism responsible for the evolution is shown to be a balance of two dynamical effects which compete to bring the network to a nonrandom critical steady state. Unlike other proposed evolutionary mechanisms that select for canalization, this mechanism does so while maintaining the system's capacity for further evolution in the steady state.

Computer Simulation↗

PubMed2006

Haplotype block structure is conserved across mammals.

Genetic variation in genomes is organized in haplotype blocks, and species-specific block structure is defined by differential contribution of population history effects in combination with mutation and recombination events. Haplotype maps characterize the common patterns of linkage disequilibrium in populations and have important applications in the design and interpretation of genetic experiments. Although evolutionary processes are known to drive the selection of individual polymorphisms, their effect on haplotype block structure dynamics has not been shown. Here, we present a high-resolution haplotype map for a 5-megabase genomic region in the rat and compare it with the orthologous human and mouse segments. Although the size and fine structure of haplotype blocks are species dependent, there is a significant interspecies overlap in structure and a tendency for blocks to encompass complete genes. Extending these findings to the complete human genome using haplotype map phase I data reveals that linkage disequilibrium values are significantly higher for equally spaced positions in genic regions, including promoters, as compared to intergenic regions, indicating that a selective mechanism exists to maintain combinations of alleles within potentially interacting coding and regulatory regions. Although this characteristic may complicate the identification of causal polymorphisms underlying phenotypic traits, conservation of haplotype structure may be employed for the identification and characterization of functionally important genomic regions.

Animals↗