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bioRxiv2024

Unraveling the genetic legacy of commercial whaling in bowhead whales and narwhals

Commercial whaling decimated many whale populations over several centuries. Bowhead whales (Balaena mysticetus) and narwhal (Monodon monoceros) have similar habitat requirements and are often seen together in the Canadian Arctic. Although their ranges overlap extensively, bowhead whales experienced significantly greater whaling pressure than narwhals. The different harvest histories but similar habitat requirements of these two species provide an opportunity to examine the demographic and genetic consequences of commercial whaling. We whole-genome resequenced Canadian Arctic bowhead whales and narwhals to delineate population structure and reconstruct demographic history. Bowhead whale effective population size sharply declined contemporaneously with the intense commercial whaling period. Narwhals instead exhibited recent growth in effective population size, reflecting limited opportunistic commercial harvest. Although the genetic diversity of bowhead whales and narwhals was similar, bowhead whales had more genetic diversity prior to commercial whaling and will likely continue to experience significant genetic drift in the future. In contrast, narwhals appear to have had long-term low genetic diversity and may not be at imminent risk of the consequences of the erosion of genetic diversity. This work highlights the importance of considering population trajectories in addition to genetic diversity when assessing the genetics of populations for conservation and management purposes.

genomics↗

bioRxiv2024

Resolving Paradoxes in Molecular Evolution: The Integrated WF-Haldane (WFH) Model of Genetic Drift

Genetic drift, the random changes in frequencies of neutral variants, is the fundamental force of molecular evolution. Under-estimation of genetic drift is a major cause of mis-conclusions on evolution. However, the standard Wright-Fisher (WF) model of random sampling in population of size N only partially defines genetic drift with 1/N or 1/Ne (Ne being a function of varying N's). In parallel, JBS Haldane proposed the branching process for genetic drift (Haldane 1927), whereby each gene copy is transmitted to K descendants with the mean and variance of E(K) and V(K). Genetic drift in its essence is V(K), i.e., the variance in transmission success, or V(K)/N when averaged over the population. Under the general WF models (i.e., the standard model as well as the many modifications), paradoxes have emerged. They include: i) Most curiously, genetic drift may often become stronger as N becomes larger at the ecological time scale, opposite to the model; ii) Sex chromosomes experience drift differently even with the same normalized N; iii) Genetic drift operates on advantageous mutations depends on V(K) but not on N; iv) Irresolution and paradoxes emerge in multi-copy gene systems, including diploidy, viruses and others, whereby evolution progresses both within and between individuals (Wang, et al. 2024). We now show that the integration of the WF and Haldane (i.e., WFH) model can resolve these paradoxes. Most important, the WFH model can fully define genetic drift in molecular evolution.

evolutionary biology↗

bioRxiv2024

Tree sequences as a general-purpose tool for population genetic inference

As population genetics data increases in size new methods have been developed to store genetic information in efficient ways, such as tree sequences. These data structures are computationally and storage efficient, but are not interchangeable with existing data structures used for many population genetic inference methodologies such as the use of convolutional neural networks (CNNs) applied to population genetic alignments. To better utilize these new data structures we propose and implement a graph convolutional network (GCN) to directly learn from tree sequence topology and node data, allowing for the use of neural network applications without an intermediate step of converting tree sequences to population genetic alignment format. We then compare our approach to standard CNN approaches on a set of previously defined benchmarking tasks including recombination rate estimation, positive selection detection, introgression detection, and demographic model parameter inference. We show that tree sequences can be directly learned from using a GCN approach and can be used to perform well on these common population genetics inference tasks with accuracies roughly matching or even exceeding that of a CNN-based method. As tree sequences become more widely used in population genetics research we foresee developments and optimizations of this work to provide a foundation for population genetics inference moving forward.

evolutionary biology↗

bioRxiv2024

Genetic diversity and connectivity of the invasive gastropod, Callinina georgiana (Caenogastropoda: Viviparidae) across a fragmented riverscape: a mitonuclear perspective.

O_LIAquatic Invasive Species (AIS) are a significant threat to global freshwater biodiversity. This study focuses on the banded mystery snail, Callinina georgiana, an invasive species in the Adirondack region of northern New York - an important section of the New York Great Lakes Basin. This project aims to explore the genetic connectivity of C. georgiana within its invasive range using a combination of mitochondrial and nuclear markers. C_LIO_LISampling was conducted in the Raquette River and adjacent waterways, with a total of 229 snails collected from 16 distinct populations distributed across eight different waterbodies. Also included were two populations from the species native range in the southern United States. DNA was extracted, and a 710 bp fragment of the mtDNA marker COI and a 351 bp fragment of nuclear marker Histone-3 (H3) were amplified. Population genetic analyses including haplotype patterning, AMOVA and genetic diversity estimates, neutrality tests and tests for isolation by distance (IBD) were performed to assess connectivity patterns. C_LIO_LIResults showed moderate to high levels of genetic admixture within the snails invasive range as indicated by the lack of geographic patterning of haplotypes and low to moderate levels of genetic differentiation across multiple sites. Demographic analyses combined with high numbers of private haplotypes indicate population expansion. Interestingly, a case of mitonuclear discordance was detected for native and invasive populations as evident by incongruent haplotype patterns for the COI and H3 markers. C_LIO_LICallinina georgiana exhibits a high level of genetic connectivity in its invasive range. The presence of dams does not significantly affect gene flow, indicating that anthropogenic activities, such as boat traffic might be key in dispersing the snails across this fragmented freshwater system. C_LIO_LIThis study offers new insights into the dispersal and genetic structure of an invasive freshwater snail. It highlights the importance of considering anthropogenic factors when confronting complex patterns of genetic diversity. The findings are significant for biodiversity conservation and provide a basis for developing strategies to manage and contain the spread of AIS like C. georgiana, especially in regions with high human activity. C_LI

ecology↗

bioRxiv2024

The effect of host population genetic diversity on variation in metrics of parasite success

According to conventional wisdom, disease transmission rate is usually higher in more genetically homogenous host populations. Previous studies have principally considered how host population genetic diversity impacts the mean of parasite infection performance. However, when considering risks from epidemics and the emergence of novel infectious diseases, variability in parasite success may be just as important as the mean. Here we propose an Epidemic Diversity Model for how host-parasite population genetic diversity influences both the mean and variability in parasite success. We evaluate this conceptual model by re-analysing effect size data from two meta-analyses, including 211 comparisons of high versus low genetic diversity host populations from 48 studies. Our analysis challenges previous understanding by demonstrating that high host population genetic diversity only reduces mean parasite success for specialist parasites with narrow host range, but not for generalist multi-host parasites. We also find that the combination of host range and parasite population genetic diversity determine the effect of host population genetic diversity on the variability in parasite success. These results have important implications for the management of host population genetic diversity for natural populations.

ecology↗

bioRxiv2024

A pluripotent stem cell platform for in vitro systems genetics studies of mouse development

The directed differentiation of pluripotent stem cells (PSCs) from panels of genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact of natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines and experimental approaches for modeling embryonic development in a genetically diverse, outbred mouse stock (Diversity Outbred mice). We show that a range of inbred and outbred PSC lines can be stably maintained in the primed pluripotent state (epiblast stem cells -- EpiSCs) and establish the contribution of genetic variation to phenotypic differences in gene regulation and directed differentiation. Using pooled in vitro fertilization, we generate and characterize a genetic reference panel of Diversity Outbred PSCs (n = 230). Finally, we demonstrate the feasibility of pooled culture of Diversity Outbred EpiSCs as "cell villages", which can facilitate the differentiation of large numbers of EpiSC lines for forward genetic screens. These data can complement and inform similar efforts within the stem cell biology and human genetics communities to model the impact of natural genetic variation on phenotypic variation and disease-risk.

developmental biology↗

bioRxiv2024

Sporadic distribution of a new archaeal genetic code with all TAG codons as pyrrolysine

Numerous genetic codes developed during the evolution of Eukaryotes and three are known in Bacteria, yet no alternative genetic code has been established for Archaea. Some bacterial and archaeal proteins include selenocysteine or pyrrolysine, the 21st and 22nd amino acids, but no evidence establishes the adoption of a genetic code in which a stop codon universally encodes either amino acid. Here, we used proteomics to confirm the prediction that certain Archaea consistently incorporate pyrrolysine at TAG codons, supporting a new archaeal genetic code which we designate Genetic Code 34. This genetic code has 62 sense codons encoding 21 amino acids, and only two stop codons. In contrast with monophyletic genetic code distributions in bacteria, Code 34 occurs sporadically. This, combined with evidence for lateral gene transfer of the code change machinery and anticipated barriers to code reversal, suggests Code 34 arose independently in multiple lineages. TAG codon distribution patterns in Code 34 genomes imply a wide range in time since code switch. We identified many new enzymes containing Pyl residues, raising questions about potential roles of this amino acid in protein structure and function. We used five new PylRS/tRNAPyl pairs from Code 34 archaea to introduce new-to-nature pyrrolysine analogs into proteins in E. coli, demonstrating their utility for genetic code expansion. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/615893v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@f363a5org.highwire.dtl.DTLVardef@112f061org.highwire.dtl.DTLVardef@63ad59org.highwire.dtl.DTLVardef@9eddb_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2024

Genetic diversity and fine-scale structure of two populations of a subterranean rodent, Ellobius talpinus

Subterranean rodents represent an interesting model system for molecular ecologists. Their lifestyle is associated with fragmented environments, limited dispersal ability, and low fecundity. These characteristics all are expected to increase inter- and intrapopulation differentiation and reduce intra- population genetic diversity, yet the published empirical data revealed the lack of generality of this pattern. This emphasizes the importance of accumulating more data on individual species to understand what factors shape the genetic dynamics of populations. This study represents the first characterization of the population genetic diversity and fine-scale genetic structure of a highly specialized subterranean vole, Ellobius talpinus. We used nine microsatellite loci and a fragment of the mitochondrial D-loop to investigate genetic patterns of two distant populations: the Novosibirsk population at the extreme northeastern edge of the species range, and the sub-peripheral Saratov population. As a result, the two populations exhibit distinct patterns of genetic structure. The Novosibirsk population showed a low nuclear diversity with an observed heterozygosity (Ho) of 0.34 and an unbiased expected heterozygosity (uHe) of 0.55. Mitochondrial D-loop was nearly monomorphic with over 90% of the observed haplotypes being identical, resulting in a haplotype diversity (Hd) of 0.14 and nucleotide diversity ({pi}) of 0.0004. In contrast, the Saratov population displayed moderate nuclear (Ho = 0.64; uHe = 0.76) and high mitochondrial variation (Hd = 0.83;{pi} = 0.034), compared to the surface-dwelling voles. Nine haplotypes representing four well-differentiated mitochondrial clades were found in the Saratov population. In a heterogeneous landscape, significant genetic differentiation was revealed at both intermediate (dozens of kilometers) and fine (several kilometers) scales. However, within the continuous suitable habitat, no fine-scale spatial structure was observed apart from that caused by kin clustering. The spatial genetic patterns revealed in E. talpinus appear to reflect a combination of effects of strong social structure, local natural and anthropogenic barriers limiting dispersal opportunities, and occasional long-distance dispersal.

zoology↗

bioRxiv2024

Whole-genome evaluation of genetic rescue: the case of a curiously isolated and endangered butterfly

Genetic rescue, or the translocation of individuals among populations to augment gene flow, can help ameliorate inbreeding depression and loss of adaptive potential in small and isolated populations. Genetic rescue is currently under consideration for an endangered butterfly in Canada, the half-moon hairstreak (Satyrium semiluna). A small, unique population persists in Waterton Lakes National Park, Alberta, isolated from other populations by >350km. However, whether genetic rescue would actually be helpful has not been evaluated. Here, we generate the first chromosome-level genome assembly and whole-genome resequence data for the species. We find that the Alberta populations genetic diversity is extremely low and very divergent from the nearest populations in British Columbia and Montana. Runs of homozygosity suggest this is due to a long history of inbreeding, and coalescent analyses show that the population has been small and isolated, yet stable for up to 40k years. When a population maintains its viability despite inbreeding and low genetic diversity, it has likely undergone purging of deleterious recessive alleles and could be threatened by their reintroduction via genetic rescue. Ecological niche modelling indicates that the Alberta population also exhibits environmental associations that are atypical of the species. Together, these results suggest that population crosses are likely to result in outbreeding depression. We infer that, in this case, genetic rescue has a relatively unique potential to be harmful rather than helpful at present. However, due to reduced adaptive potential, the Alberta may still benefit from future genetic rescue as climate conditions change. Proactive experimental population crosses should be completed to assess reproductive compatibility and offspring fitness.

ecology↗

bioRxiv2025

Uniform bacterial genetic diversity along the guts of mice inoculated with human stool

Environmental gradients throughout the digestive tract shape spatial variation in the composition and abundance of bacterial species along the gut. However, much less is known about how genetic diversity within bacterial species is distributed along the gut. Understanding this distribution is important because bacterial genetic variants confer traits that influence both microbiome function and host physiology, including local inflammation and nutrient metabolism. Thus, to understand how the microbiome functions at a mechanistic level, it is essential to understand how genetic diversity is organized along the gut. In this study, we profiled genetic diversity of approximately 30 common gut commensal bacteria in five regions along the gut lumen in germ-free mice colonized with the same healthy human stool sample. Although species composition varied considerably along the gut, genetic diversity within species was substantially more uniform. Driving this uniformity were similar strain frequencies along the gut, implying that multiple, genetically divergent strains of the same species can coexist within a host without spatially segregating. Additionally, the approximately 60 unique evolutionary adaptations arising within mice tended to sweep throughout the gut, showing little gut region specificity. We then analyzed metagenomic samples collected along the guts of conventional mice and healthy humans and found similar dynamics with their natural microbiomes, suggesting that uniform bacterial genetic diversity may be common to multiple host species. Together, our findings demonstrate that uniform spatial distribution of genetic diversity along the gastrointestinal tract is a robust feature of mammalian gut ecosystems.

microbiology↗

bioRxiv2025

Influence of past climate changes and human-mediated introduction on patterns of genetic diversity distribution of the Papuan nutmeg (Myristica argentea) Warb.

Understanding the distribution of genetic diversity of endemic food tree species holds significant importance for conservation planning and the formulation of effective management strategies. Natural and anthropogenic factors can influence species geographic range and distribution of genetic diversity. Here, we tested the relative influence of barriers to gene flow (rivers, mountains and past climate change) and recent human activities on the evolutionary history of an endemic species from Fakfak district, Papua Island, Myristica argentea Warb (Myristicaceae), better known as Papuan nutmeg. Myristica argentea is a spice tree species used by local populations since centuries/millennia. The species has been introduced in other locations from the region. Fourteen microsatellite markers (nSSRs), whole chloroplast (cp) genome, and nuclear-targeted sequence genes (nrDNA sequence) were used to characterize the genetic diversity, population structure, and demographic history of the species across its distribution range (native and introduced populations). We found that native populations of the species in Fakfak present higher levels of genetic diversity than introduced populations. We further detected the presence of a moderate genetic structure (FST = 0.143), and the presence of three intraspecific genetic clusters. Additionally, our findings indicate that population fragmentation within the native range of the species in Fakfak, may have been influenced by the presence of riparian networks, mountain ranges and by Pleistocene climatic fluctuations. Our results suggest that all introduced populations were sourced mainly from the native population of Raduria, in the South of Fakfak region. Given the population genetic variation across the ranges of Papuan nutmeg, management plans should not treat them as single populations, but rather consider the broader genetic diversity within its range.

evolutionary biology↗

bioRxiv2025

A genetically-diverse mouse model reveals a complex gene-environment regulation of cognitive resilience and susceptibility to Alzheimer disease

Alzheimers disease (AD) has a complex etiology arising from largely unknown interactions between genetic and environmental (GxE) factors. Even in populations with causal familial Alzheimers disease mutations, there is variation in disease onset and progression, suggesting that clinical symptoms are modified by genetics and environment. Identification of such modifiers is critical, as mechanisms that promote resilience to high-risk AD mutations, unhealthy diet, or aging represent promising therapeutic targets for AD; global resilience factors that protect against multiple "hits" are among the highest priority for discovery. Both genetic and environmental protective factors in AD have been identified; however, GxE factors are incredibly difficult to study in human populations given complex genomes, poor self-reporting, limited data from underrepresented groups, and incompletely documented exposomes. Here, we (1) validate novel GxE tools using population of mouse strains that model the polygenic nature of human AD, (2) characterize individuals with cognitive resilience to high-risk genetic and dietary perturbations, (3) define and quantitate roles for genetics, sex, age, and diet, and (4) present data for the discovery of complex interactions that are nearly impossible to elucidate from humans or inbred mice. We found that a high-fat high-sugar (HFHS) diet is not universally damaging, as some strains showed an improved AD-related cognitive outcome when fed a HFHS diet, suggesting the need for personalized recommendations for dietary interventions in AD. Cognitive resilience to AD is polygenic; however, we found a locus on Chr 10 that was modestly associated with cognitive resilience to AD in females, and this association was strengthened by HFHS diet, pointing to an unexpected interaction between specific genetic loci and unhealthy diet in AD risk and resilience. This study is the first of its kind to explore characteristics of AD resilience and GxE interactions in a genetically diverse mouse model. We present a subset of strains that exemplify global cognitive resilience to be leveraged for deep mechanistic studies aimed toward development of resilience-based, personalized therapeutic interventions. HighlightsO_LIAD-BXD mouse models and data repository provide unprecedented tools for understanding individual differences arising from Gene x Environment factors in aging and AD. C_LIO_LIEvidence of global cognitive resilience to AD-relevant outcomes that is partially mediated by a resilience to aging and dietary risk factors. C_LIO_LICognitive resilience in AD-BXDs its polygenic nature, with a modest locus on Chr 10 whose association with resilience was amplified by a high-fat/high-sugar diet. C_LIO_LIThe genetic factors mediating resilience to AD in humans also predict cognitive resilience in AD-BXDs, suggesting robust, translatable global resilience factors. C_LI

neuroscience↗

bioRxiv2025

Evaluating genetic-ancestry inference from single-cell RNA-seq data

Characterizing the ancestry of donors in single-cell transcriptomic studies is crucial to ensure genetic homogeneity, reduce biases in analyses, identify ancestry-specific regulatory mechanisms and their downstream roles in disease, and ensure that existing datasets are representative of human genetic diversity. While these datasets are now widely available, information on the ancestry of donors is often missing, hindering further analysis. Here, we propose a framework to evaluate methods for inferring genetic-ancestry from genetic polymorphisms detected in single-cell sequencing reads. We demonstrate that widely used tools (e.g., ADMIXTURE) provide accurate inference of genetic-ancestry and admixture proportions, despite the limited number of genetic polymorphisms identified and imperfect variant calling from sequencing reads. We infer genetic-ancestry for 401 donors from ten Human Cell Atlas datasets and report a high proportion of donors of European ancestry in this resource. For researchers generating single-cell transcriptomic datasets, we recommend reporting genetic-ancestry inference for all donors and generating datasets that represent diverse ancestries.

bioinformatics↗

bioRxiv2025

Beyond genetic indicators: how reproductive mode and hybridization challenge freshwater mussel conservation

Genetic diversity is a fundamental component of biodiversity that should be monitored and preserved. Unionid freshwater mussels provide essential ecosystem services but are among the most imperilled aquatic organisms worldwide. Here, we assess key genetic Essential Biodiversity Variables (EBVs)--genetic diversity, genetic differentiation, inbreeding, and effective population size--in all Anodonta species in Switzerland. After generating draft genomes for Anodonta cygnea and Anodonta anatina, we performed whole-genome resequencing of 421 individuals (243 A. anatina, 151 A. cygnea, 17 A. exulcerata and 10 Anodonta sp.) from 31 populations. While A. anatina populations followed a metapopulation structure shaped by catchment areas, genetic diversity correlated positively with waterbody size, suggesting greater vulnerability in small ponds compared with large lakes. Inbreeding levels were low, however effective population sizes were consistently below 100, indicating serious extinction risks. We also detected hybridization between A. cygnea and A. exulcerata, indicating genomic permeability between these species. Furthermore, genomic data suggested facultative selfing in A. cygnea, leading to a marked reduction in genetic diversity, increased population structure and inbreeding, and a decline in effective population size compared to the outcrossing A. anatina, emphasizing that A. cygnea faces a particularly high risk of extinction due to its reproductive strategy. Our study reveals the vulnerability of freshwater mussels and emphasizes the need for genetic indicators to reflect species-specific reproductive strategies. More broadly, it calls for conservation policies to integrate genetic monitoring and consider reproductive modes to tailor conservation efforts and better assess extinction risks.

genomics↗

bioRxiv2025

Genetic differentiation in Anopheles stephensi from India and Ethiopia: insights from mitochondrial genome analysis

Anopheles stephensi is a primary malaria vector, particularly in urban areas of South Asia and the Middle East. Its recent spread into Africa has raised significant interest in understanding its genetic structure and evolutionary history. This study presents a comprehensive analysis of 98 mitochondrial genomes of An. stephensi from India, Pakistan, and Ethiopia, providing critical insights into the species genetic diversity patterns. High genetic diversity was observed among Indian samples, with two distinct genetic ancestries identified. While one ancestry was more prevalent in specific geographical regions, both lineages were found across all study sites, suggesting the co-existence of multiple lineages within these areas. Further analysis revealed significant genetic differentiation between Indian and Ethiopian populations, with limited overlap in shared mutations. Although some Ethiopian samples showed genetic relatedness to the SDA500 strain from Pakistan (used in genome sequencing by the Broad Institute), the majority of Ethiopian samples showed distinct genetic ancestry. The distinctiveness of Ethiopian populations, compared to other countries outside of Africa, was also reflected in the COI datasets analyzed in this study. However, further expanding the mitogenome dataset to include additional wild samples from regions such as Pakistan, Iran, Saudi Arabia, Sri Lanka and other African countries will provide a more comprehensive understanding of An. stephensis invasion history. Overall, the findings of this study highlight the significant genetic differentiation between Ethiopian and Indian An. stephensi populations, and existence of multiple lineages in Ethiopia indicating multiple independent introductions from different countries.

zoology↗

bioRxiv2025

Development, validation, and evidence of frequent exchange of mating type HD alleles of Puccinia striiformis f. sp. tritici provide an insight into highly genetic diversity

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a worldwide destructive wheat disease. It possesses the potential to generate novel virulence races through sexual reproduction, which is the primary cause of its extensive epidemics. Mating type (MAT) of Pst lacks direct experimental evidence to account for the role of sexual recombination on high genetic diversity in evolution. Herein, we developed 11 pairs of HD alleles of Pst MAT genes, and 2 pairs HD alleles of P. striiformis f. sp. hordei (Psh, the causal agent of barley stripe rust) MAT genes. HD alleles in Pst are different from those in Psh. We tested that mating system of Pst is tetrapolar responsible for sexual genetic recombination via HD genes by experiments of selfing and sexual hybridization on alternate (secondary) hosts. Multiple HD gene types and HD gene recombination types were detected in Chinese natural Pst populations of 200 Pst isolates and 13 Psh isolates from 92 sampling sites in 11 provinces, supporting that sexual reproduction accounts for frequent emergence of new races and high genetic diversity of Pst population in northwestern oversummering variable region (hotspot) than other stripe rust-occurring regions in China. Overall, these results provide an insight into diverse types and frequent exchange of Ps MAT alleles, revealing the important role of sexual recombination via MAT alleles in virulence variation, high genetic diversity and epidemics of Pst, and also provide a basis for wheat stripe rust control in those regions where sexual reproduction occurs. Author summaryHeteroecism of the wheat stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst) was discovered a decade ago. The significance of sexual reproduction in maintaining genetic diversity has emerged as a pressing concern in contemporary scientific discourse. In this study, we elucidated the presence of multiple HD gene types (HD1 linked to HD2) in Puccinia striiformis f. sp. tritici (Pst), distinguishing it from P. striiformis f. sp. hordei. Through biological experiments on sexual reproduction, we demonstrated that the mating system of Pst is tetrapolar. Furthermore, we observed that sexual reproduction, particularly selfing (individual race) and crossing (between two races), facilitates sexual recombination via HD genes, leading to pathogenic variation and a high level of genetic diversity. We established a model illustrating sexual reproduction of Pst by selfing and crossing, respectively. In China, we have observed that the Pst population exhibits a diverse range of HD gene types and HD gene recombination types. Notably, northwestern oversummering variable regions (hotspot) have a higher number of HD genes compared to other epidemic region. Population structure and cluster analyses based on HD genes indicate that Pst populations in Tibet and Xinjiang are distinct from those in other inland regions. These findings provide valuable insights into comprehending the intricate interplay between sexual reproduction and genetic diversity of Pst, thereby elucidating the reasons behind the high genetic diversity of the Chinese Pst population.

microbiology↗

bioRxiv2025

Drivers of genetic diversity across the marine tree of life

Why do some species have more genetic diversity than others? This question is one of the greatest remaining mysteries in evolutionary biology, yet we still know little about what factors predict genetic diversity among species. Efforts to quantify diversity or understand its distribution have been hampered by a lack of genomic data analyzed in a consistent way with statistical approaches that can move beyond the population level to generate species-wide estimates of genetic diversity. We address this critical gap by generating standardized estimates of genomic-level genetic diversity for 93 species sampled over 9,000 localities. Because marine species have evolved a strikingly diverse array of biological traits that have long been hypothesized to affect species-level genetic diversity, we focus our study on marine taxa. For each species, we aggregated biotic traits related to life history and abiotic features of the species range. We show that genetic diversity increases with species range extent and planktonic dispersal. We hypothesize that these traits increase a species ability to avoid or recover from bottlenecks, thereby maintaining genetic diversity. Our findings provide insights into how biotic and abiotic factors interact to shape genomic variation in the ocean, and offer a predictive framework for understanding marine biodiversity in the face of global change. Significance statementSpecies exhibit vast trait diversity that allows populations to persist. However, diversity in these traits -- e.g., how organisms reproduce, disperse, and feed -- is not easily linked to what is known of genomic diversity, even in well-studied organisms. We investigate a diverse assemblage of marine species to begin to build a predictive framework for how species traits drive genomic diversity across the worlds oceans. We find that species with larger geographic ranges have higher genomic diversity. More dispersive species also harbor higher diversity, suggesting that greater dispersal facilitates resilience to environmental change. As available datasets increase, our ability to understand fundamental links between trait and genetic diversity and how they shape species responses to environmental change will continue to improve.

evolutionary biology↗

bioRxiv2025

A pathway-informed mutual exclusivity framework to detect genetic interactions in pediatric cancer

BackgroundThe exponential increase of sequenced cancer genomes has enabled the in-silico study of genetic interactions in tumors across many cancer types - particularly synthetic lethality, where two gene alterations lead to cell death - and identify new candidate therapeutic targets. This rise is primarily present in adult cancer, while in-silico investigation of genetic interactions remains challenging in pediatric cancer especially in tumors of low incidence. Consequently, this underscores the need for specialized approaches to advance our understanding of genetic interactions in pediatric oncology. MethodsHere, we present the pathway-informed genetic interaction framework (PIGI) that employs mutual exclusivity and co-occurrence testing and leverages biological pathways to infer candidate genetic interactions. Pathways facilitate the detection of hidden biology by grouping genes in functional units, as well as alleviate key confounders of these analyses: pathway epistasis and cancer subtypes - thereby highlighting genes of greater interest. ResultsPIGI detected candidate genetic interactions by assessing pathway mutual exclusivity and co-occurrence in two primary pediatric cancer datasets, DKFZ and TARGET. PIGI detected, from high significance pathway relationships, 35 mutually exclusive and 2 co-occurring mutated gene pairs. The already known ME gene pair of TP53-DROSHA is detected in the much smaller collection of the DKFZ Wilms tumors. Over half of the identified gene pairs represent new discoveries that have not been previously described in the literature. Four of them could be promising candidates for synthetic lethal genetic interactions. ConclusionThese findings highlight the benefits of genetic interactions inference by exploring a different aspect of pediatric cancer data through pathways and propose new gene pairs for follow-up synthetic lethality experimentation.

bioinformatics↗