Using the ancestral recombination graph to study the history of rare variants in founder populations.

The nucleotide-binding site (NBS) gene family is central to plant innate immunity. However, a comprehensive understanding of its evolutionary dynamics and functional diversity in maize, particularly within a pan-genomic context, remains limited. We conducted a systematic pan-genomic analysis of the ZmNBS gene family across 26 representative maize inbred lines. Our approach integrated evolutionary genetics, structural variation analysis, and expression profiling to investigate presence-absence variation (PAV), duplication modes, evolutionary rates, and the impact of structural variants (SVs). We observed extensive presence–absence variation (PAV), distinguishing conserved “core” subgroups (ZmNBS31 and ZmNBS17-19) from highly variable ones (ZmNBS1-10 and ZmNBS43-60), thereby supporting a “core-adaptive” model of resistance gene evolution. Duplication mode analysis revealed subtype-specific preferences: canonical CNL/CN genes largely originated from dispersed duplications, while N-type genes were enriched in tandem duplications. Evolutionary rate analysis showed that whole-genome duplication (WGD)-derived genes exhibited strong purifying selection (low Ka/Ks), whereas tandem and proximal duplications (TD/PD) showed signs of relaxed or positive selection. Structural variants (SVs) were associated with altered motif structures and significantly impacted gene expression. Notably, ZmNBS31 emerged as a conserved, highly expressed gene under both stressed and control conditions, underscoring its potential role in basal immunity. Our findings demonstrate how duplication mechanisms, structural variations and differential selection pressures collectively shape the evolution of the ZmNBS gene family. The identification of ZmNBS31 as a candidate for basal immunity, along with our established "core-adaptive" framework, provides valuable insights and a conceptual foundation for identifying and improving broad-spectrum resistance genes in maize breeding programs.

Evolutionary genetics meets ecological immunology: insights into the evolution of immune systems.

ABSTRACTAmino acids are the building blocks of proteins that perform essential physiological functions. Theory suggests that the proteome composition—the amino acid frequencies across all proteins in a genome—is associated with an organism's optimal growth temperature, offering insights into species' temperature limits. This hypothesis, however, is largely based on prokaryotic models and has not been thoroughly tested in complex multicellular eukaryotes, where many amino acids must be acquired through diet. Here, we integrated multiple databases and analysed amino acid frequencies in the proteomes of orthologous and non‐orthologous genes from 35 Lepidoptera species to test for correlations with maximum observed temperatures and diet breadth. Using a robust phylogenetic comparative approach, we found no evidence that proteome composition correlates with temperature or diet breadth, which are important ecological traits for Lepidopterans and affect their interactions with other species. These results suggest that, unlike in simpler organisms, animal proteome composition is shaped more strongly by intrinsic biophysical and energetic constraints than by ecological factors such as temperature exposure or dietary specialisation. Our study bridges evolutionary genetics with ecological physiology across a diverse group of insects and highlights the importance of publishing well‐designed null results. These findings also emphasise the limitations of using proteome composition as a proxy for ecological adaptation in multicellular species, while opening avenues of future research to further explore the complex interplay between genetics, physiology, and environment in shaping biodiversity.

BackgroundAs key components of insects’ energy storage and mobilization systems and their various membranes, lipids are crucial to diverse phenotypes and fitness components of these metamorphic, poikilothermic organisms. Yet little is known about the ecological and evolutionary genetics of insect lipids. Historically, assay methodologies have been unable to resolve the diverse components of their lipidomes.ResultsWe have used modern lipidomics to screen for heritable differences in adult male Bactrocera tryoni, examining over 400 lipids in 15 different classes of neutral and phospho- ester and ether lipids. We found substantial differences in most classes between populations recently collected from opposite extremes of the species’ range and/or during their subsequent domestication. Differences were found in both newly emerged and sexually mature flies. The differences in the former reflect differential use of resources accumulated in the larval stage during metamorphosis. The differences in the latter also reflect differential utilization of adult food resources. Most of the differences were found in the newly emerged flies and there was no obvious relationship between the differences at the two stages, implying largely independent genetic controls. The differences in lipid compositions seen among the recently collected strains suggest that lipids have played significant roles in ecotypic variation. In particular, differences in the acyl chain compositions of the phospholipids could have underpinned differences in the fluidity of the flies’ membranes in the tropical versus temperate populations sampled. There were also many differences between the source populations in the patterns of change in their lipid profiles during domestication, suggesting they adapted in different ways to the ‘common garden’ laboratory environment; acyl chain compositions in lipids from the different populations converged, but their relative abundances did not.ConclusionThe diverse patterns of genetic variation described here are consistent with the complex, multi-gene pathways for lipid syntheses and remodeling now being discovered by other insect ‘omic’ analyses and show that heritable lipid differences could underpin differences in a wide variety of adaptively important insect phenotypes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12862-025-02433-4.

The natural world is full of valuable lessons about genetic adaptation as organisms respond to changing conditions around them. Deciphering these changes is a major goal of evolutionary genetics. Advances have been made through phylogenomic approaches using the wealth of closely related genome sequences in mammals. These studies bring us lessons about the adaptive capacity allowed by the evolutionary process as well as the underlying genetic mechanisms controlling important traits. Diverse methods are now routinely used to identify the genetic basis of these adaptations. These reveal new functions of genes and regulatory regions that have responded to changes in lifestyle, such as aquatic life and flight, as well as major life history axes, such as lifespan. Phylogenomic studies have been equally revealing of specific traits that evolve in response to different selective pressures, such as hair formation and vocal learning. These approaches continue to develop to overcome challenges inherent in information-poor regulatory regions to find changes to gene regulatory networks as well. The development of these approaches is expected to accelerate as new tools, such as machine learning models, are incorporated and deployed on ever denser phylogenies containing new interesting traits.

Objective: To analyse the symptoms of Bardet-Biedl Syndrome, and to check the association of BBS10 (Bardet-Biedl syndrome 10 gene), BBS6 (Bardet-Biedl syndrome 6 gene) and BBS12 (Bardet-Biedl syndrome 12 gene) with the pathogenesis of Bardet-Biedl Syndrome. Method: The case-control study was conducted in Karachi in 2019-20, and comprised Bardet-Biedl Syndrome patients and healthy controls from the same family. Blood was drawn from all the subjects for deoxyribonucleic acid extraction. Genotyping was performed by conventional and tetra primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) to identify the possible genetic variations. To validate the results, samples were randomly selected and sent for sequencing. Data was analysed using SPSS 20, while sequencing data was analysed using the Molecular Evolutionary Genetics Analysis X software. Results: Of the 20 subjects with mean age 15.8+/-5.09 years (range: 9-25 years), 8(40%) were cases and 12(60%) were controls. The male-to-female ratio was 1:1. Pedigree analysis revealed that the pattern of inheritance was autosomal recessive. All the 8(100%) cases were obese compared to the controls. Truncal obesity, polydactyly, learning impairment and dysmorphic features, renal pain, olfactory dysfunction, respiratory tract infection and dysphasia were observed in all the 8(100%) cases. The globally reported genetic variants of BBS10 (rs1057516628 and rs1489342987) and BBS12 (rs121918327 and rs587777802) did not indicate any association with the clinical phenotype in the family concerned. The genetic variations of BBS6 (rs1547, rs1545 and rs1351192494), BBS12 (rs309370, rs2292493) and a BBS10 variant (rs35676114) had significant association with the disease. Conclusion: The genetic variations showed confounding effects of BBS10, BBS6 and BBS12 genes which might indicate the epistatic effects of other variants present on different loci. Key Words: Bardet-Biedl syndrome, BBS10, BBS6, BBS12, Genetic variations, Polymorphism.

A key insight of evolutionary genetics is that the evolvability of a population depends crucially on the amount and distribution of heritable phenotypic variation across traits. Because this insight focuses on segregating variation, the traits that don't vary among individuals but differ among higher taxa are ignored. Slowly evolving traits, like body plan organization and homologs, are nevertheless essential because they set the phenotypic boundary conditions within which variation segregates. Therefore, understanding long-term evolutionary change requires understanding the principles that control variation in varying AND conserved traits, in addition to understanding how drift and selection influence segregating population variation. In this perspective, I propose that this understanding is attainable if we acknowledge that different processes, which map sequence variation to phenotypic variation, have different capacities to produce variation and evolve. I suggest decomposing the GP map according to types of processes with different variational properties. For vertebrates, these are: morphogenesis, growth, and maintenance. This perspective allows us to focus on how these processes interact under the influence of natural selection and delineate the conditions leading to different patterns of evolutionary change.

We review recent findings pertaining to alternative RNA splicing, the formation of multiple distinct transcripts from a single gene, in order to judge its contribution to plant evolution and diversity. Alternative splicing (AS) is not only a key mechanism in plant development and stress response, but splicing variation often has a genetic basis, setting the stage for evolution involving splicing changes. Numerous examples involving crop species suggest that strong artificial selection often promotes splicing divergence, and splicing changes have affected key domestication traits. Examples of AS underlying adaptation and speciation in wild plants also exist but are fewer. These intriguing findings highlight the need for continued research at the intersection of gene regulation, splicing, and evolution to fully characterize the role of AS in plant diversification.

Nikolai Koltsov and his work, which anticipated many ideas in modern cellular and molecular biology, genetics, and epigenetics. Toward the 100th anniversary of the concept of template biosynthesis.

Environmental conditions shape phenotype and fitness, influencing which mutations rise in frequency, the maintenance of genetic diversity, and evolutionary outcomes. When the combined impact of two environments deviates from expectations based on their individual effects, this is known as an environment-by-environment interaction. While the terms “gene-by-gene interaction” and “gene-by-environment interaction” are widely recognized, “environment-by-environment interaction” is a term used less often. In this study, we find that environment-by-environment interactions are a meaningful driver of phenotypes, and moreover, that they differ across genotypes (suggestive of environment-by-environment-by-genotype interactions). To support this conclusion, we analyzed a large dataset of approximately 1,000 mutant yeast strains with varying degrees of resistance to different antifungal drugs. Our findings reveal that the effectiveness of a drug combination, relative to single drugs, often differs across drug-resistant mutants. Even mutants that differ by only a single nucleotide change can have dramatically different drug × drug interactions. Understanding how environment-by-environment interactions change across genotypes is crucial not only for modeling the evolution of pathogenic microbes but also for understanding the sources of phenotypic variance within populations. While the significance of environment-by-environment-by-genotype interactions has been overlooked in evolutionary and population genetics, these fields and others stand to benefit from understanding how these interactions shape the complex behavior of living systems.

Significant body size variations exist among different primate species. To investigate the genes influencing primate body size evolution, this study employed evolutionary genetics approaches to analyze functional differences and natural selection patterns of genes across species with distinct body sizes. Six primate species representing significant size variations were selected. Through comparative analysis of genome, molecular evolution and RNA-seq, Bcl-2 gene was detected and it has a significant impact on primate body size. Results demonstrated a positive correlation between Bcl-2 gene expression levels with body size, with differential natural selection observed among species of varying sizes. Population genetic analysis identified specific Bcl-2 SNP loci associated with body size evolution, and cellular experiments confirmed that this gene regulates osteoblast proliferation through pathways such as Wnt/β-catenin and BMP signaling. Multi-omics analysis further revealed that Bcl-2 expression increases with body size and exhibits significant selection signals and physicochemical property differences between species with substantial size variations. Functional studies indicated that Bcl-2 plays a crucial role in body size evolution by regulating skeletal development-related pathways. This study systematically reveals Bcl-2 as a key regulatory factor influencing primate adaptive body size evolution through processes such as apoptosis, skeletal development, and metabolism. From an evolutionary genetics perspective, it elucidates the molecular mechanisms underlying body size differences, providing new insights into primate body size evolution.

The interplay of tissue mechanics and gene regulatory networks in the evolution of morphogenesis.

Simple SummaryBdelloid rotifers are important model organisms for evolutionary and ecological research, yet their laboratory cultivation has traditionally relied on nutritionally variable natural food sources, limiting mechanistic studies of host–microbe interactions. This study developed a chemically defined Synthetic Rotifer Medium (SRM) that supports population growth of Adineta vaga comparable to traditional food-based systems. Using this standardized platform, we isolated and identified 20 bacterial strains from A. vaga, comprising 11 endozoic and 9 epizoic isolates. Antibiotic treatment experiments demonstrated that bacterial clearance remained incomplete while simultaneously reducing rotifer population growth. This work establishes key resources—a defined cultivation medium and a bacterial strain collection—which provide a foundation for future investigations into rotifer-microbial interactions and coevolutionary processes.Bdelloid rotifers are model organisms for evolutionary genetics; however, their laboratory cultivation has been limited to traditional systems that require natural food sources (e.g., lettuce juice, bacteria, or yeast) of undefined composition. This constraint impedes mechanistic studies of rotifer–microbe interactions and genetic evolution. We developed a synthetic rotifer medium (SRM) that enables axenic cultivation of Adineta vaga, the most commonly used model species of bdelloid rotifers in the laboratory, as a chemically controlled alternative. A. vaga reached a population density of 357 ± 19.95 ind./mL with a specific growth rate of 0.2131 ± 0.003 over 20 days in SRM, achieving parity with traditional food-supplemented systems while eliminating compositional variability. We further isolated 20 bacterial strains associated with SRM-cultured A. vaga, which were affiliated with two genera (Pseudomonas and Aquincola) on the body surface, as well as four genera (Lentzea, Streptomyces, Sphingomonas and Spirosoma) and one family (Burkholderiaceae) inside A. vaga. Additionally, the addition of low-concentration antibiotics over 20 days reduced the population size or specific growth rate of A. vaga, and cannot fully eliminate the associated bacteria. This study established the first nutritionally autonomous, compositionally stable culture system for bdelloids, enabling precise investigation of rotifer–microbe coevolution and functional genetics.

This paper models the genetical evolution of individual behavioral rules that guide the choice of strategies in pairwise assortative interactions under incomplete information. Building on results at the crossroads of evolutionary theory and game theory, it is first shown that in an uninvadable population state of behavioral rule evolution, individuals are compelled to use strategies that are Nash equilibria of a lineage fitness game. Thus, choice behavior evolves to be representable as the maximization of a utility function, as if each individual holds a personal preference that orders both their own and their interaction partner's strategies. Second, the paper contrasts two representations of personal utility that are found to be uninvadable. The first is semi-Kantian in form. This preference averages a fitness self-interest with a relatedness weighted Kantian interest. The latter interest evaluates the consequence of own behavior for own fitness, assuming the interaction partner adopts the same behavior as self. The second preference is a personal inclusive fitness. This preference combines a self-regarding interest with a relatedness weighted other-regarding interest. Each such interest takes the form of an average effect, which evaluates the consequence of expressing own behavior, instead of average population behavior, on a statistical average fitness to self and the interaction partner.

The distribution of fitness effects (DFE) describes the proportions of new mutations that have different effects on fitness. Accurate measurements of the DFE are important because the DFE is a fundamental parameter in evolutionary genetics and has implications for our understanding of other phenomena like complex disease or inbreeding depression. Current computational methods to infer the DFE for non-synonymous mutations from natural variation first estimate demographic parameters from synonymous variants to control for the effects of demography and background selection. Then, conditional on these parameters, the DFE is then inferred for non-synonymous mutations. This approach relies on the assumption that synonymous variants are neutrally evolving. However, some evidence points toward synonymous mutations having measurable effects on fitness. To test whether selection on synonymous mutations affects inference of the DFE of non-synonymous mutations, we simulated several possible models of selection on synonymous mutations using SLiM and attempted to recover the DFE of non-synonymous mutations using Fit∂a∂i, a common method for DFE inference. Our results show that the presence of selection on synonymous variants leads to incorrect inferences of recent population growth. Furthermore, under certain parameter combinations with pervasive selection on synonymous mutations, the inferred DFEs for non-synonymous mutations show an inflated proportion of highly deleterious and nearly-neutral mutations. However, this bias can be eliminated if the correct demographic parameters are used for DFE inference instead of the biased ones inferred from synonymous variants. Our work demonstrates how unmodeled selection on synonymous mutations may affect downstream inferences of the DFE.

Leishmania tropica is causing cutaneous leishmaniasis (CL) from North Africa to India and in Ethiopia and is reported to be transmitted from humans to humans through sand fly bites. While this species is characterized by a high genomic diversity all over the area of endemicity, there is very little information on diversity at micro-epidemiological scale. Here, we zoomed on an epidemic Moroccan focus of CL and studied transmission patterns by comparative genomics of parasites in human patients. We used a culture-independent method of genome sequencing, applied directly on dermal scrapings. We identified 7 groups of nearly identical genotypes, as well as parasites with mixed ancestry. Our results reveal a micro-focal transmission among humans, underlain by (pseudo) clonal and sexual reproductive modes. This study demonstrates the power of direct genome sequencing for evolutionary genetics at a micro-epidemiological scale.

Evolutionary trade-offs—opposing trait effects on total fitness via different fitness components—are likely to be widespread. Some key trade-offs are expected to be the result of chains of causation acting across an organism’s lifetime. For example, a trait imparting reproductive benefits early in life may trade off against reduced survival to attain later-life reproductive opportunities. Tools in evolutionary quantitative genetics have recently been developed to formally characterize selection acting through different causal pathways throughout the life cycle and, therefore, to formally characterize evolutionary trade-offs. We use these methods to investigate a trade-off between early life reproduction and survival and how that trade-off affects selection on body size in the Soay sheep population inhabiting St Kilda (Outer Hebrides, Scotland). We decompose and quantify the total effects of first-year female body mass on lifetime fitness, with particular attention to the effect of body mass on early-life reproduction and the potential survival cost of early-life reproduction. Our results establish that the total effect of body mass on lifetime fitness is positive, despite the strong negative contribution acting via early life reproduction. Moreover, we show that the magnitude of the selection on body mass acting through different causal paths highly depends on population density. At higher densities, the cost of early-life reproduction is higher, and therefore, it contributes a strong negative component to the total selection of body mass—i.e., at higher population density, selection on body mass is weaker than it is when the population density is smaller. By decomposing total selection and quantifying selection acting through different causal paths, we expose the underlying mechanics shaping body mass in Soay sheep female lambs, and we provide a meaningful contribution to the understanding of the evolution of body size in this population.

This article examines the mutational process from the standpoint of dialectical materialism, challenging the prevailing notion of mutation as a purely random phenomenon. By analyzing classical and contemporary biological data—such as the Cairns experiment on adaptive mutation, stress-induced mutagenesis (SOS response), and the molecular action of nucleotide analogs—it becomes clear that the environment plays a fundamental role not only in selecting but also in initiating mutations. This insight reframes mutagenesis as a materially conditioned and environmentally mediated process. Through dialectical categories such as necessity, contingency, and the “whole and moment” framework, the paper integrates philosophical analysis with empirical data to propose a systemic, causally intelligible theory of mutation. The implications of this approach extend to evolutionary theory, genetics, and systems biology.

The Varied Solitaire (Myadestes coloratus Nelson, 1912) is a near-threatened bird species, endemic to the highlands of eastern Panama and the Colombian border. In this study, we report the complete mitochondrial genome of M. coloratus. The mitogenome exhibits a typical avian structure with a slight AT bias and a control region. Phylogenetic analysis confirms the close relationship between M. coloratus and other thrush (Turdidae) species, including the extinct M. myadestinus. This data is crucial for future research on the evolutionary history and population genetics of M. Coloratus. These findings are particularly relevant as the species is increasingly threatened by human expansion.