Biology subjects

Corbett-Detig, R.

Publications and source records attributed to Corbett-Detig, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Accretion of novel genetic elements reverses genome erosion and enables host-switching in the deep sea

Endosymbiont genome erosion is driven by relaxed selection and isolation from free-living relatives' gene pools, and can be stalled by horizontal transmission events, but it remains unknown whether genome erosion can be reversed. The chemosynthetic gammaproteobacterial symbionts of deep-sea clams in the family Vesicomyidae offer a useful test case for whether eroded symbiont genomes can acquire novel functional content. Despite having some of the smallest genomes among marine endosymbionts, several lines of evidence, including divergent 16S rRNA variants within hosts, host-switching in sympatry, and phylogenetic signatures of repeated host transitions, suggest these symbionts retain more environmental exposure and evolutionary flexibility than expected under strict vertical transmission. Here, we use comparative genomics across the vesicomyid symbionts to test for evidence of functional gene gain. We find that three lineages have each independently expanded their genomes by approximately 25% relative to close relatives, with some expansions driven by insertion sequence (IS) or phage acquisition. The genomes that contain IS elements have disrupted genome synteny genome-wide, suggesting that these elements mediated structural rearrangements through ectopic recombination. Most strikingly, the symbiont of a thyasirid clam host, Thyasira sp. Haima SOB, harbors four unusually large (~24-40 kb), highly repetitive genes with structural homology to adhesins found broadly across prokaryotes and eukaryotes. These genes show hallmarks of horizontal acquisition and IS-mediated mobilization, and their predicted export via a Type I secretion system suggests a role in mediating attachment to, or exchange of metabolites across, host cell surfaces. Considering that this symbiont lineage switched from a vesicomyid host to a thyasirid host relatively recently, and thyasirids typically host extracellular symbionts, these adhesins may have been instrumental in this host-switch. Together, these findings provide evidence that genome erosion in intracellular symbionts is not strictly unidirectional, and mobile genetic elements can serve as vectors for functional innovation, potentially enabling adaptation to new hosts and environments even after substantial genome reduction has occurred.

evolutionary biology↗

bioRxiv2026

Real-time accessible phylogenetics for every highly sampled virus

The scale of viral genome sequencing has outpaced the phylogenetic tools traditionally used to analyze it, as highlighted by the COVID-19 pandemic. We present viral_usher, a unified framework for scalable viral phylogenetics built on UShER. viral_usher is a containerized command-line tool that constructs mutation-annotated trees directly from public sequence repositories with minimal user input, building phylogenies of tens of thousands of genomes in minutes. Applying it across the International Nucleotide Sequence Database Collaboration, we assembled viral_usher_trees, a repository of 446 phylogenies spanning 163 well-sequenced viral species, rebuilt automatically monthly as new genomes are deposited. We extended Taxonium from a tree viewer into a web platform supporting in-browser phylogenetic placement and de novo tree construction, so that users can upload sequences and contextualize them within global phylogenies without local computational infrastructure. Because every tree is built by the same procedure, the repository enables comparative analyses across the breadth of viral diversity. We demonstrate the utility of this resource by asking what factors shape viral mutation spectra. We found that replication machinery, captured as Baltimore class, explains 46% of the variance across 162 viral genomes, while host taxon and envelope status together explain under 5%. These resources provide an extensible platform for real-time genomic epidemiology and for comparative evolutionary analysis across viral pathogens. Resources and code are freely available at https://taxonium.org/, https://github.com/lilymaryam/spectrum_analysis, https://github.com/AngieHinrichs/viral_usher_trees, and https://github.com/AngieHinrichs/viral_usher.

bioinformatics↗

bioRxiv2026

Ultra-accurate sequencing reveals an extreme transmission bottleneck in a deep-sea clam symbiosis

Vertically transmitted symbionts experience progressive genome degradation driven by transmission bottlenecks each host generation that reduce genetic diversity and promote fixation of deleterious mutations. Direct estimates remain rare because inference requires scarce parent-offspring samples and sequencing sensitive enough to detect rare variants. Here, we investigate symbiont transmission bottlenecks in a vesicomyid clam by deeply sampling within-host endosymbiont genetic diversity using two ultra-accurate sequencing methods. Demographic modeling revealed an effective bottleneck size of approximately eight symbionts (95% CI: 1-17 genomes) per host generation. This estimate is sharply reduced relative to prior cytological estimates of bottleneck census size, with important implications for understanding the rate and dynamics of endosymbiont genome degradation.

genomics↗

bioRxiv2026

EMS Mutation and SNP Detection in Intracellular Wolbachia Genomes

Endosymbiotic bacteria such as Wolbachia pose significant challenges to genetic and molecular investigation due to their obligate intracellular lifestyle and complex growth requirements.Current understanding of their protein biology relies heavily on functional assignments inferred by homology, which may not reflect the specific roles endosymbiont proteins play within the host. This work addresses the need for robust genetic perturbation by demonstrating the successful application and detection of chemical mutagenesis in the genome of the wMel strain of Wolbachia grown within a stably infected Drosophila melanogaster JW18 cell line. To accurately detect EMS-induced mutations in a large, unsorted cell culture population, in which mutations remain at very low allele frequency, we implemented an ultra-low error rate sequencing strategy, circle sequencing. This technique enables confident detection of EMS-induced single nucleotide polymorphisms (SNPs) that would be swamped by the inherent error rates of standard next-generation sequencing. Circle sequencing library preparations successfully revealed a clear EMS mutation signal in treated cells, characterized by a significant enrichment of canonical C/G>T/A transitions. Furthermore we present a model explaining observed EMS mutation rates across the genome for different sequence contexts. These findings show that EMS-treatment can successfully leave detectable mutation signals in intracellular genomes, and offer promise for the future development of protocols to make targeted edits in Wolbachia genomes. ImportanceAs the use of intracellular symbionts for bioengineering projects grows, so does the need for foundational protocols for the genetic manipulation of intracellular genomes. Ethyl methanesulfonate (EMS), a chemical mutagen, has been a research tool for initial genomic analysis of gene function in plant and animal systems for decades and represents an established way of generating mutations for future functional testing.

genomics↗

bioRxiv2026

Panmap: Scalable phylogeny-guided alignment, genotyping, and placement on pangenomes

Pangenomes capture population-level variation but remain computationally challenging at scale. We present Panmap, a tool that leverages evolutionary structure to place, align, and genotype sequencing reads against mutation-annotated pangenomes containing up to millions of genomes. Panmap introduces a phylogenetically compressed k-mer index that stores only sequence differences along branches, enabling efficient comparison of reads to both sampled genomes and inferred ancestors. This approach reduces index size by up to 600-fold and construction time by over three orders of magnitude relative to existing tools. Panmap places a 100x coverage SARS-CoV-2 sample onto 20,000 genomes in 0.4 seconds and onto 8 million genomes in under two minutes. Furthermore, it enables accurate haplotype identification and abundance estimation in metagenomic samples and sensitive placement of ancient environmental DNA without prior alignment. Our approach makes large-scale pangenomes directly amenable to read mapping, genome assembly, alignment-free phylogenetic placement, and metagenomic analysis.

bioinformatics↗

bioRxiv2026

Interactive exploration of biobank-scale ancestral recombination graphs with Lorax.

Ancestral Recombination Graphs (ARGs) underpin analyses of natural selection, disease association, and population history but remain difficult to explore at biobank scale. We introduce Lorax, a GPU-accelerated, web-native platform for real-time visualization of population-scale ARGs. Lorax integrates genomic position, coalescent time, local genealogy, and metadata, enabling interactive exploration of ancestry and variant inheritance in biobank-scale datasets.

genomics↗

bioRxiv2025

Evidence for an ancient master sex determination gene in Hymenoptera

The vast majority of Hymenopterans determine sex by haplodiploidy, in which males and females develop from haploid unfertilized and diploid fertilized eggs, respectively. At the molecular level, the majority of Hymenoptera are thought to determine sex by so-called Complementary Sex Determination (CSD). Under CSD, sex is determined by the feminizing effects of one or more allele-rich loci, in which the feminizing function is imparted by the interactions of functionally distinct alleles. Because of high allelic diversity, most diploids are heterozygous and develop as females, whereas haploid individuals develop as males, as do rare homozygous diploids. Despite diverse empirical results suggesting that CSD is widespread in Hymenopterans, and substantial theoretical and empirical study of the consequences of CSD, the molecular biology of CSD has received little attention outside of the honeybee, Apis mellifera. Available evidence provides support for divergent perspectives ranging from a single (nearly) universally-conserved CSD locus or a pattern dominated by evolutionary turnover with different genes serving as the CSD gene(s) in different lineages. Recently, a novel non-coding RNA gene named ANTSR was shown to serve as a CSD gene in different ant lineages, and the authors suggested that ANTSR might serve as a more broadly-conserved CSD gene. To assess the role of ANTSR role in CSD across diverse Hymenoptera, we studied syntenic conservation and polymorphism patterns in the broad ANTSR locus, genome-wide sequence from available male and female diploid Formica ants, and data from a sibling cross for Bombus terrestris. We find evidence that ANTSR is a conserved CSD gene across diverse Aculeata, the largest group of Hymenoptera, and provide preliminary evidence that Formica may have multiple CSD loci including ANTSR.

genetics↗

bioRxiv2025

Extensive splicing deficiency in a degenerating mating-type chromosome

Splicing deficiency may represent a critical yet underexplored form of genomic erosion in non-recombining regions. Across four phytoplankton species diverged [~]333-639 million years ago, genes within U (female) and V (male) "UV" mating-type regions--non-recombining chromosomal regions that determine mating compatibility--show strikingly elevated intron retention relative to genes in other genomic regions. Long-read data reveal abundant aberrant, likely non-functional mRNA isoforms despite preserved coding potential. This preservation suggests that splicing defects arose early in UV evolution and have persisted over deep time. We propose that these defects arise from evolutionary changes in sequence composition and chromatin organization that accompany recombination suppression, such as reduced GC content, altered nucleosome occupancy, and disrupted methylation, that collectively compromise splicing fidelity. Unlike sex chromosomes, which often degenerate through gene loss, splicing-deficient UV regions in green algae retain hundreds of genes, indicating that transcript-level dysfunction provides an alternative route to functional decay. Our results identify chromatin-mediated splicing deficiency as a novel axis of genomic erosion and position algal UV systems as models for studying how recombination suppression reshapes RNA processing fidelity in essential, non-recombining genomes.

genomics↗

bioRxiv2025

Ancient metagenomics reveals subglacial microbiomes driven by oxygen availability

Beneath Earths glaciers and ice sheets lies an aquatic realm where ice, water, rock, and microbial life interact, driving chemical reactions that can collectively influence the global carbon cycle, polar oceans, and climate. Efforts to describe subglacial microbiomes have been limited by the challenge of cleanly drilling through hundreds of meters of ice, such that only a few sites have ever been directly sampled. Here we use ancient metagenomics to present the first spatiotemporal characterization of subglacial bacteria and archaea. We extracted DNA from 25 subglacial precipitate samples, sedimentary accumulations of minerals that form in subglacial waters prior to exposure on the surface. The precipitates studied here formed between 16,000 and 570,000 years ago beneath the Antarctic and Laurentide Ice Sheets. We show that postmortem DNA damage patterns can reliably distinguish between ancient subglacial and modern surface taxa, and that this approach can enable reconstruction of subglacial microbiomes across poles and ice ages. Our analysis suggests that subglacial microbiomes are dominated by chemolithoautotrophs, ultra-small microbes, and taxa closely related to those found in deep subsurface or extreme cold and hypersaline environments. These microbiomes split into two distinct clusters distinguished by oxygen availability and redox conditions, irrespective of geography or age. Geochemical measurements of subglacial redox state, measured either indirectly via precipitate calcite Fe and Mn concentrations or directly via water reduction potential, reproduce these same two clusters exactly. Our findings describe how subglacial water redox states are held in balance by microbes, hydrology, and oxygen input from fresh subglacial meltwater, that we interpret to be controlled by the ice sheet response to past climate variations.

genomics↗

bioRxiv2025

Efficient Estimation of Nucleotide Diversity and Divergence using Depth Information

The increasing scale of population genomic datasets presents computational challenges in estimating summary statistics such as nucleotide diversity ({pi}) and divergence (dxy). Unbiased estimates of diversity require knowledge of missing data and existing tools require all-sites VCFs. However, generating these files is computationally expensive for large datasets. Here, we introduce Callable Loci And More (clam), a tool that leverages callable loci--determined from depth information--to estimate population genetic statistics using a variant-only VCF. This approach offers improvements in storage footprint and computational performance compared to contemporary methods. We benchmark clam using a large muskox dataset and demonstrate that it produces unbiased estimates of {pi} while reducing runtime and storage requirements, compared to an existing approach. clam provides an efficient and scalable alternative for population genomic analyses, facilitating the study of increasingly large and diverse datasets. clam is available as a standalone program and integrated into snpArcher for efficient reproducible population genomic analysis.

genomics↗

bioRxiv2025

Double-stranded DNA viruses may serve as vectors for horizontal transfer of intron-generating transposons

Specialized transposable elements capable of generating introns, termed introners, are one of the major drivers of intron gain in eukaryotes. Horizontal gene transfer (HGT) is thought to play an important role in shaping introner distributions. Viruses could function as vehicles of introner HGT since they often integrate into host genomes and have been implicated in widespread HGT in eukaryotes. We annotated integrated viral elements in diverse dinoflagellate genomes with active introners and queried viral elements for introner sequences. We find that 25% of viral elements contain introners. The vast majority of viral elements represent maverick-polinton-like double-stranded DNA (dsDNA) viruses as well as giant dsDNA viruses. By querying a previously annotated set of maverick-polinton-like proviruses, we show that introners populate full-length elements with machinery required for transposition as well as viral infection. Introners in the vast majority of viral elements are younger than or similar in age to others in their host genome, suggesting that most viral elements acquired introners after integration. However, a subset of viral elements show the opposite pattern wherein viral introners are significantly older than other introners, possibly consistent with virus-to-host horizontal transfer. Together, our results suggest that dsDNA viruses may serve as vectors for HGT of introners between individuals and species, resulting in the introduction of intron-generating transposons to new lineages.

evolutionary biology↗

bioRxiv2025

A phylogenetic method identifies candidate drivers of the evolution of the SARS-CoV-2 mutation spectrum

The molecular processes that generate new mutations evolve, but the causal mechanisms are largely unknown. In particular, the relative rates of mutation types (e.g., C>T), the mutation spectrum, sometimes vary among closely related species and populations. I present an algorithm for subdividing a phylogeny into distinct mutation spectra. By applying this approach to a SARS-CoV-2 phylogeny comprising approximately eight million genome sequences, I identify 10 shifts in the mutation spectrum. I find strong enrichment consistent with candidate causal amino-acid substitutions in the SARS-CoV-2 polymerase, and strikingly three appearances of the same homoplasious substitution are each associated with decreased C>T relative mutation rates. With rapidly growing genomic datasets, this approach and future extensions promises new insights into the mechanisms of evolution of mutational processes.

bioinformatics↗

bioRxiv2024

Lethal Plague Outbreaks in Lake Baikal Hunter-gatherers 5500 Years Ago

The rise of zoonotic diseases in prehistory is often associated with the Neolithic agricultural transition1,2. In particular, plague has been linked to population declines in Late Neolithic Europe3,4. Although plague is amongst the most devastating diseases in human history, early strains of Yersinia pestis, the causal agent of plague, lack virulence factors required for the bubonic form5, and their severity remains unclear. Here, we describe the oldest strains of plague reported so far, associated with two early phases of outbreaks among prehistoric hunter-gatherers in the Lake Baikal region in East Siberia, beginning from [~]5600-5400 years ago (cal. BP). These outbreaks occur across four hunter-gatherer cemeteries; the largest of these (Ust-Ida I) has a 38.7% detection rate for plague infection (39% detection across all sites). By reconstructing kinship pedigrees, we show that small familial groups are affected, consistent with human-to-human spread of the disease, and the first outbreak occurred within a single generation. Intriguingly, the infections appear to have resulted in acute mortality events, especially among children. Zoonotic transmission is separately indicated by a Brucella infection in one of the children. Interestingly, we see differences in functional genomic variants in the prehistoric plague strains, including in the ypm superantigen known from Y. pseudotuberculosis today. The new strains diverge ancestrally to all known Y. pestis diversity and push back the Y. pestis divergence from Y. pseudotuberculosis by some 2000 years6. Our results show that plague outbreaks happen earlier than previously thought and that these early outbreaks were indeed lethal. The findings challenge the common notion that high population densities and lifestyle changes during the Neolithic transition were prerequisites for plague epidemics.

genetics↗

bioRxiv2024

Compressive Pangenomics Using Mutation-Annotated Networks

Pangenomics is an emerging field that uses a collection of genomes of a species instead of a single reference genome to overcome reference bias and study the within-species genetic diversity. Future pangenomics applications will require analyzing large and ever-growing collections of genomes. Therefore, the choice of data representation is a key determinant of the scope, as well as the computational and memory performance of pangenomic analyses. Current pangenome formats, while capable of storing genetic variations across multiple genomes, fail to capture the shared evolutionary and mutational histories among them, thereby limiting their applications. They are also inefficient for storage, and therefore face significant scaling challenges. In this manuscript, we propose PanMAN, a novel data structure that is information-wise richer than all existing pangenome formats - in addition to representing the alignment and genetic variation in a collection of genomes, PanMAN represents the shared mutational and evolutionary histories inferred between those genomes. By using "evolutionary compression", PanMAN achieves 5.2 to 680-fold compression over other variation-preserving pangenomic formats. PanMANs relative performance generally improves with larger datasets and it is compatible with any method for inferring phylogenies and ancestral nucleotide states. Using SARS-CoV-2 as a case study, we show that PanMAN offers a detailed and accurate portrayal of the pathogens evolutionary and mutational history, facilitating the discovery of new biological insights. We also present panmanUtils, a software toolkit that supports common pangenomic analyses and makes PanMANs interoperable with existing tools and formats. PanMANs are poised to enhance the scale, speed, resolution, and overall scope of pangenomic analyses and data sharing.

bioinformatics↗

bioRxiv2024

Horizontal transmission of functionally diverse transposons is a major source of new introns

Specialized transposable elements (TEs), introners, are one of the major drivers of intron gain in diverse eukaryotes. However, the molecular mechanism(s) and evolutionary processes driving introner propagation within and between lineages remain elusive. We analyze 8716 genomes, revealing 1093 introner families in 201 species spanning 1.7 billion years of evolution. Introners are derived from functionally diverse TEs including families of terminal-inverted-repeat DNA TEs, retrotransposons, cryptons, and helitrons as well as mobile elements with unknown molecular mechanisms. We identify eight cases where introners recently transferred between divergent host species, and show that giant viruses that integrate into genomes may facilitate introner transfer across lineages. We propose that intron gain is an inevitable consequence of TE activity in eukaryotic lineages, thereby resolving a key mystery of genome structure evolution.

genomics↗

bioRxiv2024

Diverging Arabidopsis populations quickly accumulate pollen-acting genetic incompatibilities

The process by which species diverge from one another, gradually accumulate genetic incompatibilities and eventually reach full-fledged reproductive isolation is a key question in evolutionary biology. However, the nature of reproductive barriers, the pace at which they accumulate and their genomic distribution remain poorly documented. The disruption of co-adapted epistatic interactions in hybrids and the accumulation of selfish genetic elements are proposed contributors to this process, and can lead to the distortion of the mendelian segregation of the affected loci across the genome. In this study we detect and quantify segregation distortion across the genomes of crosses produced from a diverse sampling of Arabidopsis lyrata and A. halleri populations, two species at the early stages of speciation and that can still interbreed. We show that both the frequency of occurrence and the magnitude of distortion loci increase as the parents genetic distance from one another increases. We also observe that distorter loci evolve rapidly, as they occur not only within interspecific hybrids, but also in intraspecific hybrids produced from isolated population crosses. Finally, we identify both genome-wide non-independence and two specific genomic regions on different chromosomes where opposite distortion effects are repeatedly observed across multiple F1 individuals, suggesting negative epistasis is a major contributor to the evolution of hybrid segregation distortion. Our study demonstrates that pollen-acting segregation distortion is ubiquitous, and contributes not only to the ongoing reproductive isolation between A. halleri and A. lyrata, but also between very recently diverged populations of the same species.

genomics↗

bioRxiv2024

A Structural Proteome Screen Identifies Protein Mimicry in Host-Microbe Systems

Host-microbe systems are evolutionary niches that produce coevolved biological interactions and are a key component of global health. However, these systems have historically been a difficult field of biological research due to their experimental intractability. Impactful advances in global health will be obtained by leveraging in silico screens to identify genes involved in mediating interspecific interactions. These predictions will progress our understanding of these systems and lay the groundwork for future in vitro and in vivo experiments and bioengineering projects. A driver of host-manipulation and intracellular survival utilized by host-associated microbes is molecular mimicry, a critical mechanism that can occur at any level from DNA to protein structures. We applied protein structure prediction and alignment tools to explore host-associated bacterial structural proteomes for examples of protein structure mimicry. By leveraging the Legionella pneumophila proteome and its many known structural mimics, we developed and validated a screen that can be applied to virtually any host-microbe system to uncover signals of protein mimicry. These mimics represent candidate proteins that mediate host interactions in microbial proteomes. We successfully applied this screen to other microbes with demonstrated effects on global health, Helicobacter pylori and Wolbachia, identifying protein mimic candidates in each proteome. We discuss the roles these candidates may play in important Wolbachia-induced phenotypes and show that Wobachia infection can partially rescue the loss of one of these factors. This work demonstrates how a genome-wide screen for candidates of host-manipulation and intracellular survival offers an opportunity to identify functionally important genes in host-microbe systems.

bioinformatics↗

bioRxiv2024

Mixed Wolbachia infections resolve rapidly during in vitro evolution

The intracellular symbiont Wolbachia pipientis evolved after the divergence of arthropods and nematodes, but it reached high prevalence in many of these taxa through its abilities to infect new hosts and their germlines. Some strains exhibit long-term patterns of co-evolution with their hosts, while other strains are capable of switching hosts. This makes strain selection an important factor in symbiont-based biological control. However, little is known about the ecological and evolutionary interactions that occur when a promiscuous strain colonizes an infected host. Here, we study what occurs when two strains come into contact in host cells following horizontal transmission and infection. We focus on the faithful wMel strain from Drosophila melanogaster and the promiscuous wRi strain from Drosophila simulans using an in vitro cell culture system with multiple host cell types and combinatorial infection states. Mixing D. melanogaster cell lines stably infected with wMel and wRi revealed that wMel outcompetes wRi quickly and reproducibly. Furthermore, wMel was able to competitively exclude wRi even from minuscule starting quantities, indicating that this is a nearly deterministic outcome, independent of the starting infection frequency. This competitive advantage was not exclusive to wMels native D. melanogaster cell background, as wMel also outgrew wRi in D. simulans cells. Overall, wRi is less adept at in vitro growth and survival than wMel and its in vivo state, revealing differences between cellular and humoral regulation. These attributes may underlie the observed low rate of mixed infections in nature and the relatively rare rate of host-switching in most strains. Our in vitro experimental framework for estimating cellular growth dynamics of Wolbachia strains in different host species, tissues, and cell types provides the first strategy for parameterizing endosymbiont and host cell biology at high resolution. This toolset will be crucial to our application of these bacteria as biological control agents in novel hosts and ecosystems. Author SummaryWolbachia pipientis is one of the most common bacterial endosymbionts due to its ability to manipulate host reproduction, and it has become a useful biological control tool for mosquito populations. Wolbachia is passed from mother to offspring, however the bacterium can also "jump" to new hosts via horizontal transmission. When a Wolbachia strain successfully infects a new host, it often encounters a resident strain that it must either replace or co-exist with as a superinfection. Here, we use a Drosophila melanogaster cell culture system to study the dynamics of mixed Wolbachia infections consisting of the high-fidelity wMel and promiscuous wRi strains. The wMel strain consistently outcompetes the wRi strain, regardless of wMels initial frequency in D. melanogaster cells. This competitive advantage is independent of host species. While both strains significantly impede host cell division, only the wMel strain is able to rapidly expand into uninfected cells. Our results suggest that the wRi strain is pathogenic in nature and a poor cellular symbiont, and it is retained in natural infections because cell lineages are not expendable or replaceable in development. These findings provide insights into mixed infection outcomes, which are crucial for the use of the bacteria in biological control.

evolutionary biology↗