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bioRxiv2025

Population Genetics of Fluctuating Selection among Individuals (FSI): a New Paradigm of Molecular Evolution

The FSI (fluctuating selection among individuals) theory of population genetics postulates that the fitness effect of a mutation may fluctuate among individuals with the same genotype (heterozygote or homozygote), whereas the wildtype fitness remains a constant. We conducted a comprehensive population genetic analysis and demonstrated profound impacts on the current wisdom of population genetics and molecular evolution. First, genetic drift induced by FSI, FSI-genetic drift for short, may play an important role in molecular evolution when the Ne-genetic drift is weak, i.e., the effective population size is not very small. Second, FSI toppled the golden-standard of neutrality in molecular evolution: the substitution rate equals to the mutation rate if and only if the mutation is strictly neutral. Instead, the concept of selection-duality claims that, under FSI, slightly beneficial mutations may be subject to a negative selection, resulting in a substitution rate less than the mutations rate. Consequently, there are three types of neutrality under FSI: the fixation neutrality (substitution rate equals to mutation rate), the generic neutrality (the population mean of selection coefficient is zero), and the FSI-neutrality (the midpoint of fixation neutrality and generic neutrality). Intriguingly, our theoretical analysis shows that the null hypothesis ( = 0) of MacDonald-Kreitman (MK) test exactly corresponds to the FSI-neutrality. Rejection of the null that, say, favors the alternative > 0, could lead to two interpretations: when the observed is below a threshold, the selection-duality is favored; otherwise an adaptive evolution is favored. We calculated the threshold for several mammals (human, macaque, lemur and vole), and found that all those observed values (from 3.5% to 29%) were below the threshold and so they be interpreted by the selection duality rather than adaptive evolution.

evolutionary biology↗

bioRxiv2026

Genetic variation in a plant-parasitic nematode is associated with gene expression changes conserved across evolutionarily distant host plants

A hallmark of the interactions between endoparasites (parasites that live within plant tissue) and their hosts, is the parasites ability to hijack host gene expression to support their own existence. While a number of studies have been performed to identify plant genes that are recruited in this process, there is much that remains unknown. One mechanism by which these connections can be explored is using a traditional genetics approach - identifying connections between genetic variation and phenotype variation. To that end, we leverage experiments examining tissue from three host plants, each infected with one of two genetically distinct strains of the endoparasite Meloidogyne hapla. Using gene expression profiles, we identify plant genes that differ based on the genetic background of the parasite, and show that these signals are common across plant hosts. These results indicate that the plant genes recruited by the parasite differ according to the parasites genetic background, and that these alternative patterns are conserved across evolutionarily distant hosts. We also leverage public data to identify conserved host expression differences when comparing M. hapla-infected roots to uninfected root tissue. Finally, we demonstrate that parasite gene expression varies based on the parasites genetic background, and these signals are also conserved when inhabiting different host species.

genomics↗

bioRxiv2026

Mutualistic rhizobia harbor genetic variation for traits related to parasite infection

Nutritional mutualisms are defined by resource exchange, but growing evidence suggests that these interactions also shape resistance to parasites and pathogens. The evolutionary significance of this phenomenon is unclear, primarily because research has focused on mutualist-mediated plasticity rather than on mutualist contributions to heritable variation in the outcome of infection. To test whether nutritional mutualists harbor genetic variation for infection-related traits, we performed a quantitative genetic experiment in the nutritional mutualism between legumes and nitrogen-fixing rhizobia. We paired 10 mutualistic Sinorhizobium meliloti rhizobia strains with 20 Medicago truncatula plant genotypes in an incomplete factorial design, and experimentally infected plants with parasitic root-knot nematodes (Meloidogyne hapla). We used this design to estimate plant and rhizobia contributions to genetic variation in four infection-related traits: resistance, tolerance, virulence, and mutualism robustness to infection. Rhizobia contributed directly to genetic variation in virulence, and to parasite resistance and mutualism robustness via genotype-by-genotype interactions. Rhizobia did not contribute to genetic variation in tolerance. The effect of rhizobia on parasite resistance was partially explained by their effect on root growth. Our results raise the possibility that some nutritional mutualists play a role comparable to defensive mutualists in shaping the evolutionary potential of host defense traits. Teaser textNutritional mutualisms are everywhere. These mutualisms are defined by the exchange of resources between partners, but many have secondary effects on resistance to parasites, pathogens, or herbivores. Here, we show that a textbook nutritional mutualist (nitrogen-fixing rhizobia) harbors genetic variation for the hosts response to parasite infection. Our results imply that nutritional mutualists can impact the evolutionary potential of infection-related traits in their hosts, suggesting that these mutualisms may be overlooked drivers of defense evolution.

evolutionary biology↗

bioRxiv2026

Population structure and genetic diversity of smooth newts (Lissotriton vulgaris) in North Tyrol, Austria: influences of allochthonous individuals and conservation implications

Amphibians are threatened worldwide by various environmental and anthropogenic factors, making non-invasive conservation studies particularly valuable. Newts are one example of a thus challenged amphibian group. In Austria, local population declines of newts have been observed, with the smooth newt (Lissotriton vulgaris) being strongly affected. In this study, skin swabs were used as a non-invasive method to gather DNA, combined with established microsatellite markers. We sampled 139 L. vulgaris individuals at ten sites in North Tyrol, Austria, and, for comparison, 22 L. vulgaris meridionalis individuals in Brixen, Italy. We genotyped all individuals and analysed their population structure. We demonstrate the presence of three distinct L. vulgaris population clusters and find differences in population structure between supposedly introduced allochthonous L. vulgaris individuals and autochthonous populations, as evidenced by differences in Bayesian clustering and elevated values of the fixation index FST. A captive population in a zoological garden, with origins in the Kramsacher Loar in the Tyrolean Unterland (eastern part of Tyrol), performed poorly in terms of conservation genetics, with low genetic diversity (number of alleles) and clear genetic differentiation from populations in the wild (high pairwise FST values with wild individuals, clear separation in cluster analysis). Habitat restoration programs are a crucial aspect of amphibian conservation, as they restore ecosystems that are critical to the animals survival. While breeding programs can play an additional role in the future, they must carefully consider genetic diversity to ensure resilient and viable populations, especially in the face of climate change and chytrid fungus infection. This study emphasizes the significance of considering the geographic origin and genetic diversity of newts in conservation efforts. It also serves as a foundation for future population genetic studies of newts in Austria.

molecular biology↗

bioRxiv2026

Comparative Proteomic Analysis of Environmental and Genetic Models of Parkinsons Disease Highlights the Role of Purine Metabolism.

Parkinsons Disease (PD) is the second most common neurodegenerative disease, with many cases being attributed to environmental contaminant exposures. Paraquat (PQ), is a pesticide and environmental neurotoxicant that has been strongly associated with increased risk of PD. PQ is known to be a weak inhibitor of complex I of the electron transport chain, and while its acute toxicity is well understood, the underlying mechanism by which PQ exposure contributes to PD pathophysiology remains unclear. Additionally, the mechanism of PQ neurotoxicity has yet to be effectively compared and related to genetic forms of PD. Given that PD is a heterogeneous disease with both genetic and environmental determinants, we sought to systematically compare the proteomic changes that occur in different genetic and environmental models of PD. In this study, we leveraged untargeted omics approaches to differentiate between systemic, peripheral, and CNS-specific changes in the proteome. We did this by performing a comparative proteomic analysis on the heads and bodies of Drosophila models of PQ ingestion and neuronal -synuclein expression in males. Additionally, we validated the findings with metabolomic analysis of male and female brain stems from a murine PQ inhalation model using C57BL/6J mice. Our findings indicate shared dysregulated pathways across all models, highlighting similar mechanisms of action. Specifically, we identified a glia-specific role in purine nucleotide metabolism upstream of inosine catabolism, which may protect against PQ neurotoxicity. This work identifies potential early points for biomarker detection and potential targets for drug intervention. Significance StatementNeurodegenerative diseases such as Parkinsons disease (PD) pose a growing public health burden, yet disease-modifying therapies remain limited due to lack of mechanistic understanding and disease heterogeneity. Both genetic and environmental factors contribute to PD, complicating the identification of shared therapeutic targets. Here, we identify a convergent pathway common to genetic and environmental models of Parkinsonism that not only affects the brain but also systemically. Using integrated metabolomics, proteomics, and genome-scale metabolic modeling, we demonstrate that purine metabolism is dysregulated across models. Reverse genetic screening of key enzymes in this pathway mitigates locomotor deficits induced by neurotoxic pesticide exposure in Drosophila. These findings reveal a shared metabolic vulnerability in PD and highlight purine metabolism as a potential therapeutic target.

neuroscience↗

bioRxiv2026

MGIDI selection and machine learning reveal harvest index driving traits in sodium azide-induced rice mutants with SSR-based genetic diversity

Sodium azide mutagenesis offers a powerful approach to generate genetic diversity for rice improvement, yet comprehensive characterization of mutant populations using integrated modern breeding tools remains limited. M mutants of BRRI dhan28 induced with sodium azide, were evaluated for 17 agronomic traits and genetic diversity was characterized using 30 SSR markers. The MGIDI was used to characterize elite genotypes and machine learning approaches were used to dissect trait architecture underlying harvest index. The phenotypic variation captured by principal component analysis was 52.12%, and yield was the trait with the highest genotypic variance (278.22) and genotypic coefficient of variation (29.07%). MGIDI analysis detected 10 elite mutants that significantly outperformed within the same environment in combined yield and harvest index. The main predictors of harvest index variability were examined using a Random Forest analysis, and this showed that grain and straw yield were the main predictors of harvest index variability. The SSR markers showed high level of genetic diversity (PIC = 0.264), population structure analysis revealed two subgroups (Fst = 0.0437) and the pairwise genetic distance ranged from 0.000 to 0.733. Procrustean alignment showed a high correlation between molecular and phenotypic variation. An integrated approach of MGIDI selection and prediction of diversity using machine learning underpinned the identification of elite mutants that can be quickly forwarded to breeding programs. This study provides valuable genetic resources and demonstrates that sodium azide mutagenesis combined with modern analytical tools accelerates genetic gains in rice improvement.

plant biology↗

bioRxiv2026

Advancing Vibrio genetics: A platform for efficient genomic manipulation

Most non-model Vibrio species lack the genetic tools needed for targeted mutagenesis, which limits the ability to functionally characterize newly identified pathways. To address this challenge, we present here efficient, robust methods for genetically manipulating Vibrio species that rely on RecA-mediated homologous recombination and two well-characterized counterselection methods, galactokinase (galK) 2-Deoxy-D-galactose (DOG-2) toxicity and the rpsLR/rpsLS streptomycin susceptibility system, both of which are active across a broad range of Vibrio species. We further characterized two genus-specific conserved promoters capable of driving high-level ectopic expression across all tested species. These promoters were incorporated into two broadly applicable, conjugatively transferable suicide backbones designed to facilitate double homologous recombination. Using these systems, we successfully disrupted polar flagellar motility in multiple Vibrio species and introduced extensive modifications to both flagellar and secretory pathways in V. diazotrophicus. Notably, although the galK system exhibited broader applicability, the rpsL system proved to be more efficient in cases where a streptomycin resistant strain could be generated. We also developed two mobilizable replicative backbones that express pH-stable fluorescent proteins for use within the genus. Collectively, these tools expand the genetic toolkit available for both gene disruption and heterologous gene expression in non-model members of the Vibrionaceae. ImportanceMembers of the Vibrionaceae are not only among the most abundant and ecologically influential microorganisms in marine ecosystems, but they also represent major drivers of disease across a wide range of hosts, including humans. However, identifying the genetic determinants of Vibrionaceae pathogenesis has remained challenging due to their halophilic growth requirements, restriction enzyme profiles, and resistance to expressing foreign proteins. Canonical counterselection pathways are largely ineffective in these species, which underscores the need for novel and efficient genetic tools to advance functional studies. This study adapts two strategies previously successful in other non-model organisms for use within the Vibrio genus and its close relatives. These methods therefore represent an essential step toward overcoming long-standing genetic barriers in Vibrio species and provide a framework to expand our understanding of biology in this important bacterial genus.

microbiology↗

bioRxiv2026

Development and assessment of tailored illustrations to enhance community understandings of genetics topics

ObjectivesEffective communication about genetics concepts is essential for collaborative anthropological genetics research. However, communication can be challenging because many ideas are abstract and may be especially unfamiliar to communities with limited access to formal education. Indeed, there are no widely adopted models for communicating such information, nor a clear understanding of the social factors that may shape participant engagement. Here, we conducted a qualitative and quantitative, community-driven study to understand how illustrations can be useful to support concept sharing with two Indigenous groups--the Orang Asli of Peninsular Malaysia and the Turkana of Kenya. MethodsWe used a two phase approach to create and evaluate how illustrations can bolster communication about genetics concepts. First, we created images illustrating answers to frequently asked questions about genetics, iteratively updating the illustrations based on participant feedback. Second, we conducted 92 interviews to evaluate the finalized illustrations effectiveness. Finally, we analyzed the interview data using thematic analyses, multivariable modeling, and multiple correspondence analyses to identify patterns in participant understanding and feedback, including age, sex, market integration, and schooling. ResultsParticipants reported high interest in genetics research (92%) and broadly positive perceptions of the illustrations. Familiar, locally-grounded imagery was preferred and associated with greater perceived clarity, while more technical illustrations were more frequently reported as confusing. Quantitative analyses showed strong internal consistency across measures of engagement and understanding, with modest variation by degree of market-integration, schooling, and sex. DiscussionOur findings demonstrate that community-specific visualizations, co-developed through iterative feedback, can effectively support engagement with genetics research in participant communities.

scientific communication and education↗

bioRxiv2026

Cross-disease genetic and epigenetic architecture of the MOBP locus shows convergence in ALS-PSP

BackgroundMyelin associated oligodendrocyte basic protein (MOBP) is an abundantly expressed oligodendrocyte gene. Genetic variation at the MOBP locus has been associated with risk for multiple neurodegenerative disorders, including progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Epigenetically, MOBP promoter hypermethylation and reduced expression have been reported in multiple system atrophy (MSA). Although MOBP is thought to play a role in oligodendrocyte morphology and myelin structure, how genetic and epigenetic variation at this locus influences gene regulation and contributes to disease risk remains poorly understood across neurodegenerative disorders. MethodsWe assessed genetic overlap and colocalisation at the MOBP locus across multiple neurodegenerative diseases. Disease-associated signals were fine-mapped to prioritise putative causal variants, and the strongest signals were subsequently investigated using molecular quantitative trait loci and post-mortem brain tissue datasets. ResultsALS and PSP showed strong genetic association at MOBP, with highly overlapping associated variants and strong evidence that both diseases share the same causal signal. Overlap with frontotemporal dementia was weaker. Methylation quantitative trait locus colocalisation identified cg15069948, located near an exon junction within MOBP, as strongly colocalising with the ALS and PSP genetic risk signals. In PSP brain tissue, carriers of the rs1768208-T risk allele showed lower methylation at cg15069948. We additionally identified evidence for an interaction between rs1768208 genotype and cg15069948 methylation associated with altered MOBP 3' untranslated region architecture. ConclusionsThese findings identify a shared ALS/PSP genetic-epigenetic mechanism at MOBP that is distinct from promoter-associated dysregulation in MSA. Together, they position MOBP as a key oligodendrocyte regulatory locus with both shared and disea e-specific roles in neurodegeneration.

neuroscience↗

bioRxiv2026

Genetic architecture of cichlid brain morphology

How evolutionary and developmental processes interact to determine axes of neural variation that produce behavioural diversity has been debated for many decades, with alternative hypotheses giving differential emphasis to functional coupling, which favours co-evolution, and developmental constraint, which enforces it. A critical omission is data on the genetic architecture of brain size and structure, which more closely illuminates the shared developmental dependencies between components of an integrated system. Here, we exploit ecological divergence between Astatotilapia calliptera and Aulonocara stuartgranti, two closely related cichlid species from Lake Malawi, to explore the genetic architecture of brain evolution. Using computer vision and machine learning techniques to extract volumetric data from micro-tomographic images, we first demonstrate significant divergence in brain composition between these species. Genomic and micro-tomographic imaging data from a population of hybrids generated between the two species were used to investigate genetic factors shaping this differentiation. We show that the majority of brain components are integrated phenotypically in hybrids, but genetic correlations between them are generally weaker. We further show that variation in multiple brain components is associated with variation in largely structure-specific quantitative trait loci, rather than determined by genetic factors with broad effects across the entire brain. These results suggest a genetic architecture that can facilitate modular changes in brain structure, and imply that individual components are independently evolvable.

evolutionary biology↗

bioRxiv2026

Strategy Sets the Scene: Genetic architecture of linalool resistance in Botrytis cinerea

Botrytis cinerea is a necrotrophic fungal pathogen that infects thousands of plant species. During infection, these diverse plant hosts produce different specialized metabolites that can inhibit pathogen growth and shape pathogen fitness. However, the genetic architecture of pathogen resistance toward individual host defense metabolites remains poorly understood. To address this question, we exposed 83 B. cinerea isolates to the metabolite linalool and quantified metabolic and structural responses. Exposure revealed extensive phenotypic diversity across isolates. Population structure analysis using genome-wide SNP data showed little genetic subdivision despite diverse hosts and geographic location. Genome-wide association identified 98 genes of interest associated with membrane transport and stress response regulation. Genetic associations were stronger for morphological traits than for metabolic traits, suggesting that hyphal architecture may have a complex genetic architecture contributing to linalool resistance. Together, these results establish natural variation in linalool response and provide candidate loci for understanding how generalist pathogens respond to host-derived chemical defenses. Article SummaryTo understand how a generalist pathogen responds to host defenses, we asked how Botrytis cinerea responds to linalool, a widespread monoterpene involved in plant defense. We exposed 83 B. cinerea isolates to 1000 {micro}M of linalool for 72 hours and quantified metabolic traits (growth curves and growth dynamics over time) and morphological traits (hyphal network features). Using GWA, we linked phenotypic variation to genetic variants. Results indicate substantial natural variation in linalool resistance and distinct genetic architectures across trait classes: metabolic responses are driven by a relatively small number of loci with larger effects, whereas structural/morphological responses appear more polygenic.

genomics↗

bioRxiv2026

Contrasting patterns of seascape genetics in Acropora cf. tenuis and their symbiotic algae.

Theory suggests that pairs of mutualist species will often co-disperse and share the same dispersal patterns, though the extent to which this happens remains unclear. Photosynthetic corals constitute an example of this dynamic, as they rely on algal symbionts to meet their energetic needs, yet many acquire their symbionts environmentally after their larval dispersal phase. Consequently, corals and their symbionts may exhibit similar or contrasting patterns of genetic variation across the seascape, with implications for their evolutionary and ecological processes. Here, we densely sample corals of the key reef-building taxon Acropora cf. tenuis and their algal symbionts across a reefscape in the central Philippines to examine genetic variation across space. Four distinct coral taxa show genetic evidence of long distance dispersal, including weak or absent isolation by distance signals and parent-offspring pairs at widely spaced sites. These coral taxa all host a single group of algal symbionts from the genus Cladocopium, which shows landscape genetic structure independent from its coral hosts. In fact, Cladocopium genetics vary with both latitude and depth, potentially indicating genome-wide local adaptation at a finer spatial scale than that seen in their hosts. Genetic variation at markedly different spatial scales between host and symbiont may be beneficial for hosts if these differences enable them to acquire symbionts adapted to their settlement environments.

ecology↗

bioRxiv2026

Population genetics of bumble bee species with diverging population dynamics

Pollinator populations are facing worldwide declines, underscoring conservation needs. Yet, conservation assessments still mostly rely on occurrence data, often derived from heterogeneous and opportunistic observations. While such data can inform on species presence and distribution, they may overlook important markers of population declines. This is particularly problematic for social species such as bumble bees, which typically exhibit low effective population sizes despite high abundance of workers observed in the field. Despite these putative pitfalls, the relationship between occurrence-based and genetic-based estimates remains largely unexplored in social bees. We here investigated spatio-temporal genetic patterns in five Swiss Bombus species representing contrasting population trajectories over the last century: B. humilis and B. sylvarum (stable), B. ruderatus (increasing), B. pomorum (regionally extinct), and B. veteranus (declining). Museum specimens collected between 1929 and 2023 were genotyped at 11 microsatellite loci to compare spatio-temporal fluctuations in genetic diversity and population structure with occurrence data. Overall, multilocus heterozygosity and allelic richness remained stable in all species during the time period investigated, indicating that the diverging population trends did not result in substantial variation of genetic diversity. In contrast, strong and significant shifts in allelic frequencies between time periods were detected in three species, suggesting recent immigration events. Isolation by distance was detected in the cold-adapted B. veteranus, while the extant warm-adapted species (B. humilis, B. sylvarum, B. ruderatus) showed high levels of gene flow between locations. In B. pomorum, increasing genetic homogenization was observed before extinction. Altogether, these findings show that genetic diversity indexes are not the most adapted tools to monitor conservation status of social bee populations, and that estimates of population structure such as allelic shifts may be more informative. Moreover, these results highlight the importance of monitoring metapopulation dynamics and ensuring connectivity among populations to facilitate gene flow and enable demographic rescue processes.

ecology↗

bioRxiv2026

Adding iPSC donor lines does not adequately control for genetic heterogeneity

Human induced pluripotent stem cell (iPSC)-based disease modelling studies are widely expected to include three to five independent donor lines to control for the contribution of donor genetic background to phenotypic variance. This convention has been formalized into major guidelines, yet no power analysis has evaluated whether these sample sizes can detect, estimate, or control for donor-level genetic effects. Here, we provide that evaluation. Using Monte Carlo simulation, closed-form confidence intervals, population genetics, and empirical resampling of transcriptomic data from iPSC lines, we show that studies with three to five donors cannot reliably detect donor-level variance, cannot estimate its magnitude with useful precision, and cannot determine whether a treatment effect generalizes across genetic backgrounds. The sample sizes required to reliably detect, estimate, or control for donor-level variance exceed 20 donors and, for many phenotypes, exceed 50, well beyond what any standard disease modelling experiment can deliver. Adding two or three donor lines to a study does not meaningfully increase statistical power, narrow confidence intervals, or establish whether a treatment effect generalizes across genetic backgrounds. The inability to control for genetic background is not a limitation of individual study design but a structural property of iPSC-based modelling. We propose that the field adopt isogenic controls for variant-specific questions and orthogonal validation against clinical datasets for generalizability, rather than treating donor number as a proxy for rigour.

bioengineering↗

bioRxiv2026

Sex differences in the genetic basis of human recombination within 190,000 parent-child pairs

Structured AbstractO_ST_ABSIntroductionC_ST_ABSSexual reproduction uses a specialized cell division called meiosis, in which a single round of DNA replication is followed by two cell divisions to create hap-loid gametes. Genetic recombination in meiosis assures faithful segregation of chromosomes and establishes patterns of genetic linkage and inheritance. Meiotic recombination is thus a fundamental genomic process that shapes major features of the genomic landscape, influences mutation, and creates genetic diversity. RationaleThe genetic basis of between-individual variation in the occurrence and genomic location of meiotic recombination events remains poorly understood in humans. In particular, we lack an understanding of whether the same DNA regions shape vari-ation in recombination rates across studies. We address this by curating 112,144 maternal and 78,653 paternal meiosis events (parent-child pairs) across cohorts from four countries, creating the largest dataset of its kind. ResultsWe identify 58 independent genomic regions associated with the occurrence and genomic location of recombination events, 24 of which are unique across phe-notypes. Of the 24 unique regions, 6 are novel and specific to female meiotic recombination harboring genes linked to ovarian function, a 7th novel region is linked to male recombination. Many regions have significant sex-dependent ef-fects across studies. We estimate the between-sex genetic correlation for meiotic recombination rate to be 0.374 (0.072 SD), which captures the extent to which the genetic factors influencing a trait in one sex also impact the same trait in the other. 30-40% of the individual-level variation in recombination rate is at-tributable to DNA markers, of which only 37.7% (2.7% SD) and 47.1% (3.8% SD) is attributable to previously known global modulators of meiotic recombi-nation, in females and males respectively. We create a polygenic predictor that significantly predicts recombination rates of both women and men after adjusting for age and year of birth. We find significant correlations between female meiotic recombination, reproductive outcomes and reproductive aging, after adjusting for study ascertainment. ConclusionsIn the largest meta-analysis to date of human meiotic recombination, we identify novel loci with sex-specific effects that influence male and female recombination rate across multiple cohorts.

genomics↗

bioRxiv2026

Genetic polymorphisms in a mate choice locus are maintained by balancing selection in a wild medaka population

Sexual selection arises from individual differences in reproductive success, which can drive the maintenance of genetic polymorphisms in genes subject to balancing selection by the pleiotropic effects that trade-off between survival and reproduction. However, the extent to which sexual selection maintains genetic polymorphisms in wild populations remains unclear. Here, we explored on genomic signatures of balancing selection and selective sweep in the northern medaka, Oryzias sakaizumii in Japan by performing whole-genome resequencing of wild individuals. In addition, we re-evaluated the population genetic structure and admixture of Oryzias latipes and O. sakaizumii across the Japanese archipelago and detected genomic regions affected by introgression. Regions with signatures of selection from multiple statistics were located on eleven chromosomes. In particular, a region spanning 4.25 to 6.80 Mb on chromosome 18 showed high genetic diversity that could not be explained by sex differentiation or introgression from O. latipes in Eastern Japan. This pattern suggests that balancing selection maintains genetic polymorphisms in O. sakaizumii. Specifically, because a previously reported quantitative trait locus associated with female mating behavior overlaps with this region, we infer that sexual selection contributes to the maintenance of genetic polymorphism at this locus.

evolutionary biology↗

bioRxiv2026

Oligonucleotide genetics for Pseudomonas aeruginosa enables high throughput hypomorph screening

The continual advancement of genetic tools has been critical to our modern understanding of bacteria, with transposons, plasmids, and homologous recombination becoming workhorses of molecular microbiology. However, precisely specified reverse genetic approaches remain painstakingly slow and inaccessible, particularly in non-model strains. This reality is exemplified by the opportunistic pathogen, Pseudomonas aeruginosa (Pa), where conventional allelic exchange remains the dominant reverse genetic method. Here, we adapt a rapid genetic toolkit for use in Pa, relying directly on commercially available oligonucleotides (120 bases) to create precise genomic mutations through homologous recombination (i.e. oligo recombineering). Oligo Recombineering followed by Bxb-1 Integrase Targeting (ORBIT) uses a short attachment site for an integrating plasmid, which provides traditional antibiotic selection and can also carry flexible cargo. We establish Pa ORBIT works effectively for gene deletion without off target mutations, optimize protocol parameters (e.g. oligo length, electroporation), and demonstrate markerless and clean deletions. Importantly, our toolkit works well in clinical Pa strains as demonstrated by constructing efflux pump deletions in three different isolates. To test the high throughput capabilities of Pa ORBIT, we created over 160 degron-based hypomorphs (i.e. knockdowns) across 43 essential proteins in a pooled mutant library. Upon screening this library with and without antibiotics, we identify highly vulnerable essential proteins and hypomorphs that display synergy with clinical drugs. Therefore, ORBIT can be used for cutting edge low and high throughput investigations in this priority pathogen, setting the stage for answering critical basic and clinical science questions. SignificanceTo understand bacterial genomes, researchers need access to rapid, flexible, precise and high throughput genetic perturbation tools. Here we present an oligonucleotide-based method that satisfies these requirements for use in the opportunistic pathogen, Pseudomonas aeruginosa. By relying on oligos to encode genomic homology arms, no molecular cloning is required - making these tools rapid, robust, and scalable. We benchmark gene deletions in both lab and clinical strains, opening the possibility of rapid genetic studies across the P. aeruginosa pangenomic space. At high throughput, we use an oligo pool to create a mutant library of degron tagged essential proteins. These knockdowns (i.e. hypomorphs) show certain essential genes are highly vulnerable and others are synergistic with clinical drugs, providing insight into future antibiotic and co-therapy development.

microbiology↗

bioRxiv2026

Life-history traits may buffer genetic erosion under isolation in mountain sky-island systems

Sky-island systems provide natural case studies for understanding how geography and Quaternary history shape genomes, phenotypes and life-history traits in mountain endemics. We investigated Xatartia scabra (Apiaceae), a monotypic scree specialist plant species restricted to sky-island summits in the eastern Pyrenees, by integrating population genomics with abiotic condition-informed distribution modeling. Using a ddRAD-seq-like protocol (nGBS), we genotyped 125 individuals (21,970 SNPs), and applied species distribution modeling to identify suitable environmental conditions from the Last Glacial Maximum to 2100. Genetic analyses revealed unexpected genetic "resilience", with moderate genome-wide diversity (HE = 0.17, Ho = 0.15) and low inbreeding (FIS = 0.07), despite small census sizes and strong isolation. Significant overall genetic differentiation (FST = 0.16), with pronounced summit-level structure and strong isolation-by-distance, supports deep valleys as barriers to gene flow. Abiotic niche reconstructions recovered extensive Heinrich Stadial 1 connectivity (+ 58,4% relative to present), followed by postglacial loss of suitable habitats at lower elevations and increasing fragmentation; projections under climate change forecast contraction (-61,2%, relative to present) of climatic suitability, expected to intensify drift in small, isolated populations. Demographic inferences align with this narrative, indicating postglacial decline in effective population sizes. Taken together, genetic, climatic, and demographic evidence supports a transition from historically connected lowland corridors to modern sky islands where distance-limited drift dominates. The maintenance of moderate genetic diversity and low inbreeding under strong isolation suggests that X. scabra may have evolved life-history strategies including outcrossing and monocarpy that allow limiting genetic erosion in such extreme and fragmented environments.

genomics↗