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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2026

Genomic and pan-genomic insight into longan domestication and improvement

Longan (Dimocarpus longan) is a tropical tree in Sapindaceae family with economic importance known for its nutritous fruits. Genetic improvement of longan requires knowledge of reliable molecular markers and functional genes associated with key traits. However, it is largely impeded by lacking a complete genome and pangenome reference encompassing the broad genetic diversity in diverse longan germplasms. Here, we present a telomere-to-telomere (T2T) gap-free genome of longan cultivar Shixia and a graph-based pangenome constructed using newly assembled chromosome-level genomes of 101 accessions. We completely assemble the longan centromere regions primarily composed of Gypsy-CRM retrotransposons. The pan-genome analysis reveals 58,978 non-redundant structural variants (SVs) that exhibit signs of genomic selective sweep during longan domestication and breeding. Additionally, haplotype-resolved genome analysis suggests allele-specific gene expression associated with SV-driven changes in 3D genome architecture. Importantly, the graph-based pan-genome empowers population-scale SV genotyping and genomewide association with various longan traits. SV-GWAS revealed 12 QTLs significantly linked with longan maturity period. Among them, a 758bp insertion is located downstream of the DlDAZ gene encoding a C2H2 zinc-finger transcription factor, and DIDAZ-transgenic tomatoes showed delayed maturity. Together, our T2T genome and pan-genome provide valuable resources to facilitate longan genetic research and precise improvement.

genomics↗

bioRxiv2026

Complete chloroplast genome of African Baobab (Adansonia digitata L.): structural characterization, comparative genomics, and phylogenetic placement within Malvaceae

Chloroplast genomes are invaluable resources for plant genomic research, providing insights into genome evolution and molecular adaptation. With the growing scientific and economic interest in Adansonia digitata, a comprehensive characterization of its chloroplast is timely and necessary. A complete chloroplast genome of A. digitata was assembled, annotated, and characterized. Comparative structural analysis was conducted against other Adansonia species, and the assembly was validated through phylogenetic placement within Malvaceae. The assembled genome exhibits the canonical quadripartite organization, spanning 160,061 bp with a GC content of 36.88%, 79 protein-coding genes, 32 tRNAs, and 4 rRNAs. Repeat analysis identified 100 simple sequence repeat motifs, predominantly A/T-rich mononucleotide types (76%), alongside 50 long sequence repeats dominated by forward (26) and palindromic (17) repeats. Comparative analysis with other Adansonia species revealed conserved genome structure, with minor IR boundary shifts involving the ndhF gene, and ycf1 duplication in A. gregorii and A. grandidieri. Average nucleotide identity exceeded 99% across all Adansonia species, with near-complete similarity (ANI {approx} 99.96%) observed with the putative A. kilima. All predicted RNA editing events were nonsynonymous, dominated by C[->]U conversions (55.02%). Codon usage showed non-random synonymous preferences biased toward A/U-ending codons, driven primarily by mutational pressure with detectable gene-specific translational selection. Nucleotide diversity ({pi}) was higher in intergenic spacers (0.00490 {+/-} 0.00574) than in coding regions (0.00167 {+/-} 0.00199), with the majority of genomic regions showing no sequence variation ({pi} = 0). Substitution patterns indicated pervasive purifying selection, with relatively high but insignificant signals in matK, ycf1, accD, and rpoB. Phylogenomic analyses placed the assembled A. digitata chloroplast genome within the Adansonia lineage, consistent with its established systematic position. This study provides detailed insight into the chloroplast genome of A. digitata, and the findings will contribute towards advancing its genomic research.

genomics↗

bioRxiv2026

Genome-wide structural variants uncover strain-specific genes and evolutionary genomic determinants of a fungal maize pathogen

Genomic structural variants (SVs) are important sources of genetic diversity and contribute to the adaptation and evolution of plant-pathogenic fungi. Colletotrichum graminicola, the causal agent of maize (Zea mays L.) anthracnose, causes significant yield losses and serves as an important model for genetic studies. To investigate genomic plasticity in this pathogen, long-read genome assemblies were generated for four C. graminicola field strains collected in France, Croatia, Brazil, and Argentina and compared with the chromosome-level reference genome from the USA. Comparative analyses revealed extensive structural variation across core chromosomes, including large-scale translocations, inversions, duplications, and insertions and deletions, whereas minichromosomes showed markedly reduced collinearity among strains. Secreted proteins and predicted effectors were located significantly closer to regions affected by SVs. Approximately 174 kb of segmental duplications lacking genes were shared between core chromosome 04 and minichromosomes 11 and 13 in the reference genome but were absent from the other field strains, revealing a strain-specific structural link between core and minichromosomes. Protein clustering identified 733 candidate strain-specific genes across the reference genome. Approximately 72% of the genes annotated on the minichromosomes were strain-specific, indicating that most of their annotated genes lacked orthologous gene models in the other strains. Of the 733 candidate strain-specific genes, 492 retained homologous genomic sequences in at least one other strain and many also showed evidence of gene disruption. This pattern is consistent with lineage-specific pseudogenization and suggests that apparent gene presence-absence variation may arise through several evolutionary processes, including gene gain, gene loss and loss of gene function. Insertions and deletions in potentially regulatory flanking regions were associated with plant-pathogen interaction genes. In addition, interpretable machine learning analyses revealed a co-occurrence of duplications and LTR retrotransposons in genomic regions associated with secreted genes. This study shows that structural variation, transposable elements, and lineage-specific pseudogenization are important features of genome evolution in C. graminicola and identifies associations between genomic variation and genes involved in plant-pathogen interactions.

genomics↗

bioRxiv2026

Chromosome-scale nuclear and mitochondrial genome assemblies reveal extreme genome compartmentalization in the hazelnut pathogen Anisogramma anomala

Anisogramma anomala is an obligate biotrophic ascomycete and the causal agent of Eastern filbert blight, the most economically important disease of hazelnut in the United States. Here, we generated a chromosome-scale reference genome for A. anomala isolate OR-Ennis-d and characterized its nuclear and mitochondrial genome architecture. The 344-Mb nuclear genome was resolved into 9 predicted chromosomes and is repeat-rich, with transposable elements comprising 88.8% of the assembly. Although transposable elements are abundant, their divergence landscape and low retention of conserved protein domains support a history of past extensive transposon proliferation followed by widespread degeneration. Repeat accumulation was highly uneven and generated pronounced genome compartmentalization. Approximately half of predicted genes occur in compact, TE-poor regions with short flanking intergenic regions that are enriched for conserved BUSCO orthologs. In contrast, genes in TE-rich, gene-sparse regions with long flanking intergenic regions are enriched for carbohydrate-active enzymes, secreted proteins, and candidate secreted effector proteins, consistent with a two-speed-like genome architecture. The 462-kb mitochondrial genome is among the largest reported for ascomycetes and contains 117 introns, including an intron adjacent to cob codon 143 that may prevent acquisition of the p.G143A substitution associated with resistance to quinone outside inhibitor fungicides. Finally, we identified mitochondrial DNA insertions at 20 nuclear loci totaling at least 616.9 kb, an unusually extensive amount for a fungal genome. This chromosome-scale genome resource reveals the extreme nuclear and mitochondrial genome architecture in A. anomala and provides a foundation for investigating genome evolution and adaptation to hazelnut resistance.

genomics↗

bioRxiv2015

Genome-wide and single-base resolution DNA methylomes of the Sea Lamprey (Petromyzon marinus) Reveal Gradual Transition of the Genomic Methylation Pattern in Early Vertebrates

In eukaryotes, cytosine methylation is a primary heritable epigenetic modification of the genome that regulates many cellular processes. While the whole-genome methylation pattern has been generally conserved in different eukaryotic groups, invertebrates and vertebrates exhibit two distinct patterns. Whereas almost all CpG sites are methylated in most vertebrates, with the exception of short unmethylated regions call CpG islands, the most frequent pattern in invertebrate animals is mosaic methylation, comprising domains of heavily methylated DNA interspersed with domains that are methylation free. The mechanism by which the genome methylation pattern transited from a mosaic to a global pattern and the role of the one or two-round whole-genome duplication in this transition remain largely elusive, partly owing to the lack of methylome data from early vertebrates. In this study, we used the whole-genome bisulfite-sequencing technology to investigate the genome-wide methylation in three tissues (heart, muscle, and sperm) from the sea lamprey, an extant Agarthan vertebrate. Analyses of methylation level and the extent of CpG dinucleotide depletion of geneencoding, intergenic and promoter regions revealed a gradual increase in the methylation level from invertebrates to vertebrates, with the sea lamprey exhibiting an intermediate position. In addition, the methylation level of the majority of CpGs was intermediate in each sea lamprey tissue, indicating a high level of heterogeneity of methylation status between individual cells. In this regard, we defined the genomic methylation pattern of sea lamprey as \"global genomic DNA intermediate methylation\". The methylation features in different genomic regions, such as the transcription start site (TSS) region of the gene body, exon-intron boundaries, transposons, as well as genes grouping with different expression levels, supported the gradual methylation transition hypothesis. We further discussed that the copy number difference in DNA methylation transferases and the loss of the PWWP domain and/or DNTase domain in DNMT3 sub-family enzymes may have contributed to the methylation pattern transition in early vertebrates. These findings demonstrate an intermediate genomic methylation pattern between invertebrates and jawed vertebrates, providing evidence that supports the hypothesis that methylation patterns underwent a gradual transition from invertebrates (mosaic) to vertebrates (global).

Evolutionary Biology↗

bioRxiv2017

dRep: A tool for fast and accurate genome de-replication that enables tracking of microbial genotypes and improved genome recovery from metagenomes

The number of microbial genomes sequenced each year is expanding rapidly, in part due to genome-resolved metagenomic studies that routinely recover hundreds of draft-quality genomes. Rapid algorithms have been developed to comprehensively compare large genome sets, but they are not accurate with draft-quality genomes. Here we present dRep, a program that sequentially applies a fast, inaccurate estimation of genome distance and a slow but accurate measure of average nucleotide identity to reduce the computational time for pair-wise genome set comparisons by orders of magnitude. We demonstrate its use in a study where we separately assembled each metagenome from time series datasets. Groups of essentially identical genomes were identified with dRep, and the best genome from each set was selected. This resulted in recovery of significantly more and higher-quality genomes compared to the set recovered using the typical co-assembly method. Documentation is available at http://drep.readthedocs.io/en/master/ and source code is available at https://github.com/MrOlm/drep.

bioinformatics↗

bioRxiv2017

seq-seq-pan: Building a computational pan-genome data structure on whole genome alignment

BackgroundThe increasing application of next generation sequencing technologies has led to the availability of thousands of reference genomes, often providing multiple genomes for the same or closely related species. The current approach to represent a species or a population with a single reference sequence and a set of variations cannot represent their full diversity and introduces bias towards the chosen reference. There is a need for the representation of multiple sequences in a composite way that is compatible with existing data sources for annotation and suitable for established sequence analysis methods. At the same time, this representation needs to be easily accessible and extendable to account for the constant change of available genomes.\n\nResultsWe introduce seq-seq-pan, a framework that provides methods for adding or removing new genomes from a set of aligned genomes and uses these to construct a whole genome alignment. Throughout the sequential workflow the alignment is optimized for generating a representative linear presentation of the aligned set of genomes, that enables its usage for annotation and in downstream analyses.\n\nConclusionsBy providing dynamic updates and optimized processing, our approach enables the usage of whole genome alignment in the field of pan-genomics. In addition, the sequential workflow can be used as a fast alternative to existing whole genome aligners. seq-seq-pan is freely available at https://gitlab.com/groups/rki_bioinformatics

bioinformatics↗

bioRxiv2020

Integrated genomics and comprehensive validation reveal novel drivers of genomic evolution in esophageal adenocarcinoma

Identification of genes driving genomic evolution can provide novel targets for cancer treatment and prevention. Here we show identification of a genomic instability gene signature, using an integrated genomics approach. Elevated expression of this signature correlated with poor survival in esophageal adenocarcinoma (EAC) as well as three other human cancers. Knockout and overexpression screens confirmed the relevance of this signature to genomic instability. Indepth evaluation of TTK (a kinase), TPX2 (spindle assembly factor) and RAD54B (recombination protein) further confirmed their role in genomic instability and tumor growth. Mutational signatures identified by whole genome sequencing and functional studies demonstrated that DNA damage and homologous recombination were common mechanisms of genomic instability induced by these genes. Consistently, a TTK inhibitor impaired EAC cell growth in vivo, and increased chemotherapy-induced cytotoxicity while inhibiting genomic instability in surviving cells. Thus inhibitors of TTK and other genes identified in this study have potential to inhibit/delay genomic evolution and tumor growth. Such inhibitors also have potential to increase chemotherapy-induced cytotoxicity while reducing its harmful genomic impact in EAC and possibly other cancers.

cancer biology↗

bioRxiv2020

Genome-scale phylogeny and contrasting modes of genome evolution in the fungal phylum Ascomycota

Ascomycota, the largest and best-studied phylum of fungi, contains three subphyla: Saccharomycotina (budding yeasts), Pezizomycotina (filamentous fungi), and Taphrinomycotina (fission yeasts); organisms from all three subphyla have been invaluable as models in diverse fields (e.g., biotechnology, cell biology, genetics, and medicine). Despite its importance, we still lack a comprehensive genome-scale phylogeny or understanding of the similarities and differences in the mode of genome evolution within this phylum. To address these gaps, we examined 1,107 genomes from Saccharomycotina (332), Pezizomycotina (761), and Taphrinomycotina (14) species to infer the Ascomycota phylogeny, estimate its timetree, and examine the evolution of key genomic properties. We inferred a robust genome-wide phylogeny that resolves several contentious relationships and estimated that the Ascomycota last common ancestor likely originated in the Ediacaran (~563 {+/-} 68 million years ago). Comparisons of genomic properties revealed that Saccharomycotina and Pezizomycotina, the two taxon-rich subphyla, differed greatly in their genome properties. Saccharomycotina typically have smaller genomes, lower GC contents, lower numbers of genes, and higher rates of molecular sequence evolution compared to Pezizomycotina. Ancestral state reconstruction showed that the genome properties of the Saccharomycotina and Pezizomycotina last common ancestors were very similar, enabling inference of the direction of evolutionary change. For example, we found that a lineage-specific acceleration led to a 1.6-fold higher evolutionary rate in Saccharomycotina, whereas the 10% difference in GC content between Saccharomycotina and Pezizomycotina genomes stems from a trend toward AT bases within budding yeasts and toward GC bases within filamentous fungi. These results provide a robust evolutionary framework for understanding the diversification of the largest fungal phylum.

evolutionary biology↗

bioRxiv2020

An enormous Paris polyphylla genome sheds light on genome size evolution and polyphyllin biogenesis

The monocot family Melanthiaceae with varying genome sizes in a range of 230-fold is an ideal model to study the genome size fluctuation in plants. Its family member Paris genus demonstrates an evolutionary trend of bearing huge genomes characterized by an average c-value of 49.22 pg. Here, we report a 70.18 Gb genome assembly out of the 82.55 Gb genome of Paris polyphylla var. yunnanensis (PPY), which represents the biggest sequenced genome to date. We annotate 69.53% repetitive sequences in this genome and 62.50% of which are long-terminal repeat (LTR) transposable elements. Further evolution analysis indicates that the giant genome likely results from the joint effect of common and species-specific expansion of different LTR superfamilies, which might contribute to the environment adaptation after speciation. Moreover, we identify the candidate pathway genes for the biogenesis of polyphyllins, the PPY-specific medicinal saponins, by complementary approaches including genome mining, comprehensive analysis of 31 next-generation RNA-seq data and 55.23 Gb single-molecule circular consensus sequencing (CCS) RNA-seq reads, and correlation of the transcriptome and phytochemical data of five different tissues at four growth stages. This study not only provides significant insights into plant genome size evolution, but also paves the way for the following polyphyllin synthetic biology.

plant biology↗

bioRxiv2020

A versatile resource of 1500 diverse wild and cultivated soybean genomes for post-genomics research

With the advance of next-generation sequencing technologies, over 15 terabytes of raw soybean genome sequencing data were generated and made available in the public. To develop a consolidated, diverse, and user-friendly genomic resource to facilitate post-genomic research, we sequenced 91 highly diverse wild soybean genomes representing the entire US collection of wild soybean accessions to increase the genetic diversity of the sequenced genomes. Having integrated and analyzed the sequencing data with the public data, we identified and annotated 32 million single nucleotide polymorphisms (32mSNPs) with a resolution of 30 SNPs/kb and 12 non-synonymous SNPs/gene in 1,556 accessions (1.5K). Population structure analysis showed that the 1.5K accessions represent the genetic diversity of the 20,087 (20K) soybean accessions in the U.S. collection. Inclusion of wild soybean genomes significantly increased the genetic diversity and shorten linkage disequilibrium distance in the panel of soybean accessions. We identified a collection of paired accessions sharing the highest genomic identity between the 1.5K and 20K accessions as genomically "equivalent" accessions to maximize the use of the genome sequences. We demonstrated that the 32mSNPs in the 1.5K accessions can be effectively used for in-silico genotyping, discovering trait QTL, gene alleles/mutations, identifying germplasms containing beneficial allele and domestication selection of trait alleles. We made the 32mSNPs and 1.5K accessions with detailed annotation available at SoyBase and Ag Data Commons. The dataset could serve as a versatile resource to release the potential of the huge amount of genome sequencing data for a variety of postgenomic research.

plant biology↗

bioRxiv2021

A large-scale genome-based survey of acidophilic Bacteria suggests that genome streamlining is an adaption for life at low pH

Genome streamlining theory suggests that reduction of microbial genome size optimizes energy utilization in stressful environments. Although this hypothesis has been explored in several cases of low nutrient (oligotrophic) and high temperature environments, little work has been carried out on microorganisms from low pH environments and what has been reported is inconclusive. In this study, we performed a large-scale comparative genomics investigation of more than 260 bacterial high-quality genome sequences of acidophiles, together with genomes of their closest phylogenetic relatives that live at circum-neutral pH. A statistically supported correlation is reported between reduction of genome size and decreasing pH that we demonstrate is due to gene loss and reduced gene sizes. This trend is independent from other genome size constraints such as temperature and G+C content. Genome streamlining in the evolution of acidophilic Bacteria is thus supported by our results. Analyses of predicted COG categories and subcellular location predictions indicate that acidophiles have a lower representation of genes encoding extra-cellular proteins, signal transduction mechanisms and proteins with unknown function, but are enriched in inner membrane proteins, chaperones, basic metabolism, and core cellular functions. Contrary to other reports for genome streamlining, there was no significant change in paralog frequencies across pH. However, a detailed analysis of COG categories revealed a higher proportion of genes in acidophiles in the following categories: "Replication and repair", "Amino acid transport" and "Intracellular trafficking". This study brings increasing clarity regarding genomic adaptations of acidophiles to life at low pH while putting elements such as the reduction of average gene size under the spotlight of streamlining theory.

bioinformatics↗

bioRxiv2022

Comparative genomics support reduced-genome Paraburkholderia symbionts of Dictyostelium discoideum amoebas are ancestrally adapted professional symbionts

The social amoeba Dictyostelium discoideum is a predatory soil protist frequently used for studying host-pathogen interactions. A subset of D. discoideum strains isolated from soil persistently carry symbiotic Paraburkholderia, recently formally described as P. agricolaris, P. bonniea, and P. hayleyella. The three facultative symbiont species of D. discoideum present a unique opportunity to study a naturally occurring symbiosis in a laboratory model protist. In addition, there is a large difference in genome size between P. agricolaris (8.7 million base pairs) vs. P. hayleyella and P. bonniea (4.1 Mbp) and in GC content (62% vs. 59%). We took a comparative genomics approach and compared the three genomes of D. discoideum-symbionts to 12 additional Paraburkholderia genomes to test for genome evolution patterns that frequently accompany host adaptation. Overall, P. agricolaris is difficult to distinguish from other Paraburkholderia based on its genome size and content, but the two reduced genomes of P. bonniea and P. hayleyella display characteristics that support evolution in a host environment. In addition, all three D. discoideum-symbiont genomes have increased secretion system and motility genes that may mediate interactions with their host. Specifically, adjacent BurBor-like type 3 and T6SS-5-like type 6 secretion system operons shared among all three D. discoideum-symbiont genomes may be important for host interaction. Ultimately, our combined evidence supports that the reduced-genome D. discoideum-symbionts have evolved to be professional symbionts ancestrally adapted to their protist hosts.

evolutionary biology↗

bioRxiv2022

Prediction of the 3D cancer genome from genomic rearrangements using InfoHiC

Although cancer genomes often contain complex genomic rearrangements, its impact on tumorigenesis is still unclear, especially when they are involved in non-coding regions. Understanding 3D genome architecture is crucial for uncovering the impacts of genomic rearrangements. Here, we present InfoHiC, a method for predicting 3D genome folding and cancer Hi-C from complex genomic rearrangements. InfoHiC provides distinct interaction views of multiple contigs from the cancer Hi-C matrix. We then validated cancer Hi-C prediction using breast cancer cell line data and found contig-specific interaction changes. Moreover, we applied InfoHiC to patients with breast cancer and identified neo topologically associating domains and super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. Finally, we applied InfoHiC to pediatric patients with medulloblastoma, and found genomic rearrangements in non-coding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In summary, InfoHiC can predict genome folding changes in cancer genomes and may reveal therapeutic targets by uncovering the functional impacts of non-coding genomic rearrangements.

bioinformatics↗

bioRxiv2022

Chromosome-level genome assembly of Euphorbia peplus, a model system for plant latex, reveals that relative lack of Ty3 transposons contributed to its small genome size

Euphorbia peplus (petty spurge) is a small, fast-growing plant that is native to Eurasia and has become a naturalized weed in North America and Australia. E. peplus is not only medicinally valuable, serving as a source for the skin cancer drug ingenol mebutate, but also has great potential as a model for latex production owing to its small size, ease of manipulation in the laboratory, and rapid reproductive cycle. To help establish E. peplus as a new model, we generated a 267.2 Mb HiC-anchored PacBio HiFi nuclear genome assembly with an embryophyta BUSCO score of 98.5%, a genome annotation based on RNA-seq data from six tissues, and publicly accessible tools including a genome browser and an interactive organ-specific expression atlas. Chromosome number is highly variable across Euphorbia species. Using a comparative analysis of our newly sequenced E. peplus genome with other Euphorbiaceae genomes, we show that variation in Euphorbia chromosome number is likely due to fragmentation and rearrangement rather than aneuploidy. Moreover, we found that the E. peplus genome is relatively compact compared to related members of the genus in part due to restricted expansion of the Ty3 transposon family. Finally, we identify a large gene cluster that contains many previously identified enzymes in the putative ingenol mebutate biosynthesis pathway, along with additional gene candidates for this biosynthetic pathway. The genomic resources we have created for E. peplus will help advance research on latex production and ingenol mebutate biosynthesis in the commercially important Euphorbiaceae family. Significance statementEuphorbia is one of the five largest genera in the plant kingdom. Despite an impressive phenotypic and metabolic diversity in this genus, only one Euphorbia genome has been sequenced so far, restricting insights into Euphorbia biology. Euphorbia peplus has excellent potential as a model species due to its latex production, fast growth rate and production of the anticancer drug ingenol mebutate. Here, we present a chromosome-level E. peplus genome assembly and publicly accessible resources to support molecular research for this unique species and the broader genus. We also provide an explanation of one reason the genome is so small, and identify more candidate genes for the anticancer drug and related compounds.

plant biology↗

bioRxiv2024

3D genome organization under extreme metabolic adaptation shows variations in genome compartmentalization and looping

The cave morphs of Astyanax mexicanus have evolved a suite of distinct adaptations to life in perpetual darkness, including the loss of eyes and pigmentation loss, as well as profound metabolic changes such as hyperphagia and starvation resilience, traits that sharply contrast with those of their river-dwelling surface counterparts. While changed gene expression is a primary driver of these adaptations, the underlying role of 3D genome organization - a key regulator of gene expression - remains unexplored. Here, we investigate the 3D genome architecture of the livers of surface fish and two cavefish morphs (Pachon and Tinaja) using Hi-C, performing the first comparative 3D genomic analysis in this species. We analyzed and identified cave-specific 3D genomic features, such as genomic compartments and loops, which were conserved in both the cave populations but absent in surface fish. Integrating the 3D genome data with transcriptomic and epigenetic datasets, linked these changes to differential expression of metabolically relevant genes, such as Arhgef19 and Endog. Additionally, our study also uncovered genomic inversions unique to cavefish, potentially tied to cave adaptation. Our findings suggest that 3D genome organization contributes to transcriptomic shifts underlying cavefish phenotypes, providing a novel intra-species and morph specific perspective on 3D chromatin evolution. This study establishes a foundation for exploring how genome architecture potentially facilitates adaptation to new environments. Comparison of morphs within the same species also establishes a foundation for better understanding of how 3D genome reorganization may drive speciation and phenotypic diversity.

evolutionary biology↗

bioRxiv2025

MutBERT: Probabilistic Genome Representation Improves Genomics Foundation Models

MotivationUnderstanding the genomic foundation of human diversity and disease requires models that effectively capture sequence variation, such as single nucleotide polymorphisms (SNPs). While recent genomic foundation models have scaled to larger datasets and multi-species inputs, they often fail to account for the sparsity and redundancy inherent in human population data, such as those in the 1000 Genomes Project. SNPs are rare in humans, and current masked language models (MLMs) trained directly on whole-genome sequences may struggle to efficiently learn these variations. Additionally, training on the entire dataset without prioritizing regions of genetic variation results in inefficiencies and negligible gains in performance. ResultsWe present MutBERT, a probabilistic genome-based masked language model that efficiently utilizes SNP information from population-scale genomic data. By representing the entire genome as a probabilistic distribution over observed allele frequencies, MutBERT focuses on informative genomic variations while maintaining computational efficiency. We evaluated MutBERT against DNABERT-2, various versions of Nucleotide Transformer, and modified versions of MutBERT across multiple downstream prediction tasks. MutBERT consistently ranked as one of the top-performing models, demonstrating that this novel representation strategy enables better utilization of biobank-scale genomic data in building pretrained genomic foundation models. Availabilityhttps://github.com/ai4nucleome/mutBERT Contactyanlinzhang@hkust-gz.edu.cn

bioinformatics↗

bioRxiv2025

Pan-genome and core genome insights into AMR-Positive Salmonella Lineages from African Food Chains

Salmonella enterica is a major public health concern in Africa because of its increasing antimicrobial resistance (AMR) to multiple antibiotics that threatens effective treatment and control. In this study, we analyzed 135 publicly available antimicrobial resistant Salmonella genomes from African food sources. Using a pan genomic analysis approach, we identified a pangenome of 15,269 genes, including a core genome of [~]3.5 Mbp with 3,350 core genes (99-100% prevalence) and a substantial accessory genome comprising 183 soft-core, 1,441 shell, and 10,295 cloud genes. We found substantial genomic diversity among the AMR-positive Salmonella enterica isolates. AMR profiling revealed widespread distribution of resistance genes, with aac(6)-laa_1 present in nearly all genomes, and tet(A), sul2, and fosA71 frequently co-occurring. Core virulence genes such as invA, ssaL, and steA were nearly universally conserved, suggesting essential roles in pathogenesis. Sporadic rare virulence genes like papE, tcpC, and ybtP were present in the genome pointing to lineage-specific patterns. The presence of macrolide inactivation genes (ereA) points to a huge risk of resistance to the globally important antibiotic Azithromycin. Quorum-sensing genes, including the AI-2 system (luxS, lsrA-D, lsrK) and biofilm formation genes were widely conserved across the isolates, highlighting their potential role in adaptation and the spread of antimicrobial resistance in foodborne Salmonella in Africa. Hierarchical clustering based on core genome multilocus sequence typing (cgMLST) revealed monophyletic clades for major serovars like Enteritidis and Infantis. Shannon diversity indices revealed geographical variation in AMR gene richness, with Burkina Faso, South Africa and Tunisia showing high intra-country diversity. Our analysis identified lineage-associated accessory genes, hence providing potential markers for surveillance. This study offers valuable insights into the genomic architecture and AMR landscape of Salmonella in Africa and underscores the need for expanded genomic surveillance across diverse geographic and food production contexts.

microbiology↗