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PubMed2026

Evolutionary and resistance dynamics in oligometastatic and oligoprogressive cancer treated with stereotactic radiotherapy and systemic therapies: A systematic review and focused meta-analysis.

BACKGROUND: Oligometastatic and oligoprogressive disease treated with stereotactic ablative radiotherapy (SABR) represents a clinically heterogeneous entity. Increasing evidence suggests that anatomical definitions alone may not adequately capture underlying biological diversity. This systematic review aimed to synthesize translational evidence exploring evolutionary dynamics, resistance mechanisms, and biomarker-driven stratification in patients treated with SABR. METHODS: A systematic literature review was performed including prospective and retrospective studies evaluating translational biomarkers in oligometastatic or oligoprogressive settings treated with SABR. Studies assessing genomic, transcriptomic, circulating or immune-related biomarkers were included. Data were summarized qualitatively according to predefined translational domains: (i) evolutionary dynamics under systemic therapy pressure, (ii) baseline biological stratification, (iii) longitudinal circulating biomarkers, and (iv) systemic immune remodeling. Exploratory quantitative visual syntheses were performed using reported hazard ratios when conceptually comparable endpoints were available. RESULTS: 19 studies comprising 1527 patients were included. Across tumor types and treatment contexts, translational analyses consistently indicated that anatomically defined oligometastatic states encompass biologically distinct subgroups with different risks of systemic progression. Studies evaluating oligoprogression under ongoing systemic therapy suggested a distinction between spatially constrained resistance and systemic molecular escape, supported by circulating tumor DNA and tissue- or plasma-based molecular profiling (including genomic and transcriptomic analyses). Baseline biological features, including adverse genomic signatures and circulating biomarkers, were associated with inferior progression outcomes despite metastasis-directed therapy. Longitudinal biomarkers provided early signals of treatment response and systemic control. Immune remodeling after SABR showed context-dependent effects, both systemic immune activation and treatment-related immunosuppression reported across studies.

Humans↗
PubMed2026

Multilayered nucleotide organization reveals purifying selection and host-driven adaptation in CPV and FPV.

Since feline panleukopenia virus (FPV) is considered the most likely ancestor of canine parvovirus (CPV), comprehensive comparisons of nucleotide organization in corresponding viral genes between CPV and FPV may provide novel insights into the evolutionary dynamics underlying the divergence of these two viruses. Here, we characterize the evolutionary patterns of CPV and FPV genes across multiple levels of nucleotide organization. Both viruses exhibited highly conserved nucleotide usage at nonsynonymous sites, with Ka/Ks patterns consistent with strong purifying selection, whereas synonymous sites showed greater variability. CpG dinucleotides were markedly underrepresented across all four viral genes, suggesting host-associated selective pressure and/or intrinsic nucleotide compositional constraints. Extensive nonrandom biases in synonymous codon usage, codon neighboring nucleotide context, and codon pair usage further revealed fine-scale genomic optimization shaped by natural selection and nucleotide compositional constraints. Structural protein genes (VP1 and VP2) displayed stronger codon usage bias and higher tRNA adaptation than nonstructural genes. Moreover, CPV genes showed greater translational adaptation to feline hosts than to canine hosts. These findings highlight how closely related parvoviruses exploit flexible nucleotide organization to facilitate host adaptation while maintaining essential protein functions.

Animals↗
PubMed1989

[Evolution of Alu repeats: dynamics of distribution in genome].

A mathematical model of evolutionary dynamics of Alu repeats' number in the human genome has been worked out. The model permitted us to observe the dynamics of propagation of Alu repeats within the genome and to evaluate such important parameters of the process mentioned as the rates of transposition (insertion of new copies into the genome) and excision of repeats. The peculiarities of the control of Alu repeats' number in the genome have been discussed, based on the data obtained.

Genome, Human↗
PubMed2025

The ecology and evolution of microbial immune systems: a look on the wild vibrio side.

Natural populations of vibrio beyond the well-studied pandemic strains of Vibrio cholerae, provide a powerful model for investigating the eco-evolutionary dynamics of microbial immune systems. Their genetic diversity, ecological versatility, ease of culturability and the availability of time-series data enable detailed studies of phage-host interactions in natural contexts. This review synthesizes recent advances in vibriophage research, highlighting key findings and emerging tools. High-throughput assays and genomic tools have offered new perspectives on phage specificity, host range and the evolutionary pressures shaping these interactions. Theoretical frameworks, such as arms race and fluctuating selection dynamics, are informed by empirical data from vibrio-phage systems, with time-series sampling providing crucial insights into their temporal and spatial dynamics. A major finding is the role of mobile genetic elements (MGEs) in encoding bacterial defence systems, which shape phage-host coevolution. Discoveries like the phage satellite PICMI illustrate how MGEs facilitate the transfer of antiviral systems, influencing ecological and evolutionary dynamics. The paradox of generalist vibriophages, rare despite their broad host ranges, is also explored. By integrating experimental approaches with field observations, vibriophage research advances microbial ecology and informs sustainable applications in aquaculture and phage therapy, reinforcing vibrios as a versatile model system.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.

Bacteriophages↗
PubMed1993

Chaos and the evolution of cooperation.

The "iterated prisoner's dilemma" is the most widely used model for the evolution of cooperation in biological societies. Here we show that a heterogeneous population consisting of simple strategies, whose behavior is totally specified by the outcome of the previous round, can lead to persistent periodic or highly irregular (chaotic) oscillations in the frequencies of the strategies and the overall level of cooperation. The levels of cooperation jump up and down in an apparently unpredictable fashion. Small recurrent and simultaneous invasion attempts (caused by mutation) can change the evolutionary dynamics from converging to an evolutionarily stable strategy to periodic oscillations and chaos. Evolution can be twisted away from defection, toward cooperation. Adding "generous tit-for-tat" greatly increases the overall level of cooperation and can lead to long periods of steady cooperation. Since May's paper [May, R. M. (1976) Nature (London) 261, 459-467], "simple mathematical models with very complicated dynamics" have been found in many biological applications, but here we provide an example of a biologically relevant evolutionary game whose dynamics display deterministic chaos. The simulations bear some resemblance to the irregular cycles displayed by the frequencies of host genotypes and specialized parasites in evolutionary "arms races" [Hamilton, W. D., Axelrod, R. & Tanese, R. (1990) Proc. Natl. Acad. Sci. USA 87, 3566-3573; Seger, J. (1988) Philos. Trans. R. Soc. London B 319, 541-555].

Biological Evolution↗
PubMed1989

Sociobiology and the structural stability of behavior patterns.

A structural stability approach to population-genetic systems and to dynamic evolutionary games is attempted in order to examine the theoretical significance of sociobiological selection models. A criterion of weak selection is derived that is not restricted to differential reproduction in polymorphic systems but describes possible directions of evolutionary change in time scales governed by genetic mutation rates. The criterion applies to the problems of how the initial mutational basis of an adaptive trait may be established and how this may happen, for analogous traits, independently in different species. Two basic sociobiological concepts are reconsidered with reference to the criterion. It is shown that W. D. Hamilton's condition of increases in inclusive fitness due to altruistic interactions among kin expresses the structural instability of populations against the evolution of altruistic behavior. Using the dynamic approach to evolutionary game theory, it is demonstrated that if a behavioral phenotype is an evolutionarily stable strategy, it is structurally stable against perturbations of the fitness payoffs, provided selection is weak. These results are applied to material problems of the evolution of animal social behavior.

Animals↗
PubMed2026

A guide to understanding tumour evolution through the lens of population genetics.

Every cancer carries the history of its own evolution, hidden in its genome. Modern DNA sequencing can catalogue millions of mutations and profile tumours across space and time, but sequencing alone struggles to answer the questions that matter most: when did key adaptations emerge, how strongly were they selected, why do some tumours relapse whereas others do not, and how will the cancer evolve next? The reason is fundamental: sequencing is a snapshot, whereas evolution is a dynamic process. Bridging this gap requires moving beyond descriptive cancer genomics towards quantitative evolutionary inference. In this Review, we argue that population genetics provides the mathematical framework needed to extract evolutionary dynamics from cancer genomes. We show how models of mutation, selection and drift transform allele frequencies from descriptive measurements into quantitative estimates of clonal fitness and evolutionary timings. We discuss how these principles extend to epigenetic inheritance, plasticity and ecological interactions within the tumour ecosystem, and examine the assumptions and limitations for their application to modern sequencing data. By reframing cancer genomes as quantitative records of evolutionary processes rather than catalogues of mutations, researchers have used population genetics to provide a foundation for understanding - and ultimately predicting - the trajectories of cancer evolution.

Journal Article↗
PubMed1997

The dynamic nature of plant mitochondrial genome organization.

The characteristic features of higher plant mitochondrial genomes: size, structure, recombination activity and evolutionary dynamics, are reviewed with the emphasis on the mitochondrial DNA (mtDNA) of Phaseolus vulgaris. Among all examined eukaryotic organisms, higher plants were found to contain the largest and most complex mitochondrial genomes. The plant mtDNA structure in vivo and mechanisms of evolution are controversial. We present the currently accepted models and how these models correspond to mitochondrial genomes of several common bean lines.

DNA, Mitochondrial↗
PubMed1994

Extraordinarily polymorphic microsatellite DNA in barley: species diversity, chromosomal locations, and population dynamics.

This study was undertaken to assess the extent of genetic variation in barley simple sequence repeats (SSRs) and to study the evolutionary dynamics of SSR alleles. SSR polymorphisms were resolved by the polymerase chain reaction with four pairs of primers. In total, 71 variants were observed in a sample of 207 accessions of wild and cultivated barley. Analyses of wheat-barley addition lines and barley doubled haploids identified these variants (alleles) with four loci, each located on a different chromosome. The numbers of alleles detected at a locus corresponded to the number of nucleotide repeats in the microsatellite sequences. The numbers of alleles at two loci were 28 and 37; to our knowledge these are the largest numbers of alleles for single Mendelian loci reported in plants. Three alleles were resolved by each of the other two loci. Allelic diversity was greater in wild than in cultivated barley and surveys of two generations (F8 and F53) of Composite Cross II, an experimental population of cultivated barley, showed that few of the alleles present in the 28 parents survived into generation F53, whereas some infrequent alleles reached high frequencies. Such changes in frequency indicate that the chromosomal segments marked by the SSR alleles are under the influence of natural selection. The SSR variants allow specific DNA sequences to be followed through generations. Thus, the great resolving power of SSR assays may provide clues regarding the precise targets of natural and man-directed selection.

Alleles↗
PubMed2026

Asynchronous transitions from high-risk hepatoblastoma to carcinoma.

BACKGROUND & AIMS: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs. METHODS: We performed multi-omics profiling - including single-nucleus RNA sequencing, single-nucleus DNA sequencing, and multi-region longitudinal bulk RNA and DNA sequencing - to characterize HBC composition, evolution, and treatment response. Two-thirds of our samples were post-chemotherapy resections. RESULTS: HBCs comprise heterogeneous mixtures of HB-like, HBC-like, and HCC-like molecular cell types. Outcomes in HBC are significantly worse than in HB, and HBC cells are more chemoresistant than HB cells, with resistance shaped by their cell identity, genetic alterations, and embryonic differentiation stage. HBC cells originate from HB cells that were arrested at early hepatic stem cell development stages because of aberrant WNT signaling activation. Inhibition of WNT signaling promoted differentiation and enhanced sensitivity to chemotherapy. Furthermore, each analyzed HBC reflected a dynamic process of multiple HB-to-HBC and HBC-to-HCC transitions, underscoring their evolutionary complexity. A limitation of our study is our inability to pinpoint the role of chemotherapy-induced genome modifications. CONCLUSIONS: Multi-omics profiling of HBCs revealed key insights into their biology and composition, demonstrating that they originate from HB precursors at early hepatic stem cell development stages and that their differentiation arrest depends on sustained aberrant WNT signaling activity. IMPACT AND IMPLICATIONS: Hepatoblastomas with carcinoma features (HBCs) represent a poorly understood subset of pediatric liver tumors with mixed characteristics of hepatoblastoma (HB) and hepatocellular carcinoma (HCC). Using multi-omics profiling, we show that HBCs comprise heterogeneous mixtures of HB-like, intermediate HBC-like, and HCC-like cell populations that arise from HB precursors arrested at early hepatic stem cell developmental stages due to aberrant WNT signaling. This differentiation arrest contributes to chemoresistance and poorer clinical outcomes compared with HB. Importantly, pharmacologic inhibition of WNT signaling promoted differentiation and increased chemotherapy sensitivity, suggesting a potential therapeutic strategy. These findings refine the biological classification of HBCs and highlight differentiation-based treatment approaches for this aggressive tumor subtype.

Multiomics↗
PubMed2026

Competing subclones and fitness diversity shape tumor evolution across cancer types.

MOTIVATION: Intratumor heterogeneity arises from ongoing somatic evolution and complicates cancer diagnosis, prognosis, and treatment. Reconstructing evolutionary dynamics typically requires spatiotemporal samples, which are often unavailable in clinical settings. Computational approaches that can infer tumor evolutionary history from single-timepoint bulk sequencing data remain limited. RESULTS: We present estimating evolutionary events through single-timepoint sequencing (TEATIME), a novel computational framework that models tumors as mixtures of two competing cell populations: an ancestral clone with baseline fitness and a derived subclone with elevated fitness. Using cross-sectional bulk sequencing data, TEATIME estimates mutation rates, timing of subclone emergence, relative fitness, and number of generations of growth. To quantify intratumor fitness asymmetries, we introduce a novel metric-fitness diversity-which captures the imbalance between competing cell populations and serves as a measure of functional intratumor heterogeneity. Applying TEATIME to 33 tumor types from The Cancer Genome Atlas, we revealed divergent as well as convergent evolutionary patterns. Notably, we found that immune-hot microenvironments constraint subclonal expansion and limit fitness diversity. Moreover, we detected temporal dependencies in mutation acquisition, where early driver mutations in ancestral clones epistatically shape the fitness landscape, predisposing specific subclones to selective advantages. These findings underscore the importance of intratumor competition and tumor-microenvironment interactions in shaping evolutionary trajectories, driving intratumor heterogeneity. Lastly, we demonstrate that TEATIME-derived evolutionary parameters and fitness diversity offer novel prognostic insights across multiple cancer types. AVAILABILITY AND IMPLEMENTATION: R implementation of TEATIME is available on GitHub (https://github.com/liliulab/TEATIME) and Zenodo (https://zenodo.org/records/17422174).

Neoplasms↗
PubMed2026

Pervasive cryptic selection in the human noncoding genome.

The prevailing dogma in evolutionary genetics holds that mutations within sequences that are conserved across a phylogeny are deleterious in those species, and mutations outside are neutrally evolving. Indeed, such comparative genomic approaches have estimated that mutations in approximately 5% of the human genome experience negative selection. However, sites that have biological function in certain lineages but not in others, i.e. functional turnover, may violate this assumption since these sites may be invisible to comparative genomic approaches. Thus, the extent of such cryptic, or hidden, negative selection remains elusive. Here, we developed a statistical test to detect cryptic selection in human polymorphism data. Applying our approach to simulated data shows that cryptic selection shapes the site frequency spectrum (SFS) and the statistical detection power depends on the proportion of mutations experiencing cryptic selection, the amount of sequence tested, and the sample size. We applied our method to polymorphism data from the 1000 Genomes Project, comparing variants in putatively functional noncoding regions to those in putatively neutral regions. We detected pervasive signals of cryptic selection in putatively functional regions, even after filtering out the top 70% of conserved sites. Using simulations with varying levels of cryptic selection, we estimated the extent of genome-wide constraint in the human genome. Our approximation suggests that mutations in at least 7% of the human genome are under negative selection, which is greater than the estimates from conservation-based methods, and that many of these mutations have escaped detection by comparative genomic methods. In sum, our results highlight the evolutionary dynamic nature of the noncoding genome and suggest the need to account for functional turnover when identifying putatively neutral variants for evolutionary analyses.

Journal Article↗
PubMed1997

The design of adaptive systems: optimal parameters for variation and selection in learning and development.

Some aspects of learning and development are based on evolutionary change within the organism. In trial and error learning, variant ideas or behaviors are generated and selective filters (learning rules) choose among the population of variants. Development may, in some cases, proceed by selection within a population of variant cellular lineages. This paper analyses abstract properties of selective systems to understand the evolutionary dynamics that occur within organisms. The Price Equation and Fisher's fundamental theorem of natural selection, two of the most powerful concepts in evolutionary genetics, are applied in a general way to internal selective systems in learning and development. This analysis emphasizes generative mechanisms and selective filters as genetically controlled phenotypes of individual organisms. Generative mechanisms create the variation on which selection acts. Selective filters determine the extent to which selection within the organism optimizes organismal performance. The methods of Price and Fisher provide a general way in which to partition evolutionary change into improvements caused by selection and the tendency of high performance variants to deteriorate because of competition or environmental change. This balance between selective improvement, at a rate equal to the variance in fitness, and a matching deterioration in performance, provides general insight into the common properties of adaptive systems in genetics, learning and development. These ideas are applied to a model of honey bee foraging. This example clarifies the relation between genes and phenotypes controlled by internal selective systems.

Adaptation, Physiological↗
PubMed2025

Exploring genetic adaptation and microbial dynamics in engineered anaerobic ecosystems via strain-level metagenomics.

Genetic heterogeneity exists within all microbial populations, with sympatric cells of the same species often exhibiting single-nucleotide variations that influence phenotypic traits, including metabolic efficiency. However, the evolutionary dynamics of these strain-level differences in response to environmental stress remain poorly understood. Here, we present a first-of-its-kind study tracking the adaptive evolution of an anaerobic, carbon-fixing microbiota under a controlled engineered ecosystem focused on carbon dioxide bioconversion into methane. Leveraging strain-resolved metagenomics with an ad hoc variant calling and phasing approach, we mapped mutation trajectories and observed that the two dominant Methanothermobacter species maintained distinct sweeping haplotypes over time, most likely due to niche-specific metabolic roles. By combining population genetic statistics and peptide reconstruction, mer and mcrB genes emerged as potential drivers of archaeal strain-level competition. These findings pave the way for targeted engineering of microbial communities to enhance bioconversion efficiency, with significant implications for sustainable energy and carbon management in anaerobic systems.

Metagenomics↗
PubMed1996

[Dynamics of the haplotype frequencies in populations: study using the Monte Carlo method].

A program that simulates random genetic drift, random mating, recombination, natural selection, and mutation process was developed to study the influence of these processes on the evolutionary dynamics of haplotype frequencies in populations. The program can track nine sites, each including up to 15 alleles. The program application was illustrated by the study of frequency dynamics in the HOXB haplotypes (17q) in different populations. The simulation results confirmed the hypothesis, which was proposed on the basis of the experimental data, that, in the absence of recurrent mutations, population mixing, and natural selection, the harmonic mean of the effective population size from the moment of New World colonization up to now was more than 1000.

Alleles↗
PubMed2026

Epitranscriptomic erasers in bivalves: Evolutionary divergence and species-specific transcriptional plasticity of the ALKBH family under acute thermal stress.

The AlkB homolog (ALKBH) family of Fe(II)/α-ketoglutarate-dependent dioxygenases mediates nucleic acid demethylation, thereby governing RNA metabolism and genomic stability. Despite their pivotal roles in epitranscriptomic regulation across vertebrates, the evolutionary dynamics and functional significance of ALKBH proteins in bivalve mollusks remain largely unexplored. Here, we present a comprehensive phylogenomic analysis of 210 ALKBH genes identified across 35 bivalve species. Our analyses reveal a distinct evolutionary trajectory characterized by the lineage-specific loss of ALKBH4 and the restricted distribution of ALKBH5 to the Mytilidae family, contrasting sharply with vertebrate repertoires. Using the noble scallop (Chlamys nobilis) and Pacific oyster (Crassostrea gigas) as model systems, we demonstrate that ALKBH genes exhibit conserved spatiotemporal expression patterns, with pronounced enrichment in gonadal tissues and during metamorphic transitions, implicating these enzymes in gametogenesis and larval development. Furthermore, comparative thermal stress experiments reveal divergent transcriptional plasticity: the subtropical scallop C. nobilis mounts rapid, transient induction of ALKBH1/2/6 under heat shock, whereas the eurythermal oyster C. gigas maintains sustained ALKBH3 expression, potentially underpinning its superior thermal tolerance. Conversely, cold stress elicits bimodal regulation in C. nobilis, with ALKBH1/2 upregulation contrasting with ALKBH6/7/8 suppression. These findings illuminate the functional diversification of bivalve ALKBH genes and their potential utility as molecular biomarkers for assessing developmental competence and thermal resilience in shellfish aquaculture.

Animals↗
PubMed1996

Contingency tests of neutrality using intra/interspecific gene trees: the rejection of neutrality for the evolution of the mitochondrial cytochrome oxidase II gene in the hominoid primates.

Contingency tests of neutrality are performed using mitochondrial cytochrome oxidase II (COII) DNA sequences from hominoid primates, including humans. An intra-/interspecific haplotype tree is estimated, including a statistical assessment of ambiguities in tree topology and branch lengths. Four functional mutational categories are considered: silent and replacement substitutions in the transmembrane portion of the COII molecule, and silent and replacement substitutions in the cytosolic portion. Three tree topological mutational categories are used: intraspecific tips, intraspecific interiors, and interspecific fixed mutations. A full contingency analysis is performed, followed by nested contingency analyses. The analyses indicate that replacement mutations in the cytosolic portion are deleterious, and replacement mutations in the transmembrane portion and silent mutations throughout tend to be neutral. These conclusions are robust to ambiguities in tree topology and branch lengths. These inferences would have been impossible with an analysis that only contrasts silent and replacement vs. polymorphic and fixed. Also, intraspecific interior mutations have similar evolutionary dynamics to fixed mutations, so pooling tip and interior mutations into a single "polymorphic" class reduces power. Finally, the detected deleterious selection causes lowered inbreeding effective sizes, so arguments for small effective sizes in recent human evolutionary history based upon mitochondrial DNA may be invalid.

Animals↗
PubMed1995

Male gamete output of asexuals and the dynamics of populations polymorphic for reproductive mode.

Most asexual plants retain male sexual function, albeit at levels much lower than their sexual counterparts. This phenomenon has not typically received full representation in mathematical models of the cost of sex. We formulate and analyze a genetic model of reproductive mode in order to study the evolutionary dynamics of populations consisting of both sexual and asexual individuals. Our model incorporates levels of production and fertility of male gametes produced by individuals that are asexual in their female function, that vary from zero to a level equal to that in a sexual individual. This encompasses a range of naturally occurring situations that has been beyond the scope of most previous theoretical studies. We show that the cost of sex is frequency-dependent in many biologically relevant situations. Consequently, the fitness advantage needed for sexuals to resist invasion by asexuals may frequently be much less than twofold. However, the fitness advantage required for sexuals successfully to invade an asexual population may be much higher. Moreover, the viability/fertility advantage required by sexuals to equal the fitness of asexuals is not necessarily equal to the intrinsic cost of sex, but may be greater when asexual individuals produce fertile male gametes. We also show that panmictic populations cannot be stably polymorphic for reproductive mode when fitnesses are constant, and that the conditions for the fixation of sexual or asexual genotypes are not affected by the degree of dominance at the locus determining reproductive mode. With frequency-dependence, and no possibility of stable polymorphism, the reproductive mode that finally evolves will, in many cases, depend upon the initial frequencies of asexual and sexual individuals.

Biological Evolution↗