Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.11.04.764303

A largely shared genetic architecture underlies Saccharomyces cerevisiae persistence across different mouse host genotypes

Ehrenreich, I. M.·Bernardo, B.·Eoh, Y.·Dean, M. D.
View original source ↗Export metadata ↓

Abstract

The extent to which interactions between microbial and host genotypes shape opportunistic pathogen persistence within hosts is an important open question. To assess the contribution of these interactions to persistence, we used Saccharomyces cerevisiae , a genetically tractable model for studying opportunistic fungal persistence in mammalian hosts. A pooled panel of barcoded haploid segregants from a cross between a laboratory strain and a clinical isolate, together with both parents, was introduced intravenously into seven genetically diverse mouse strains. We measured the relative persistence of segregants in mouse brains and livers using barcode sequencing. Persistence showed transgressive segregation in both organs. On average across the two organs, yeast genotype explained 45.2% of the variance in segregant persistence, whereas yeast genotype-by-host genotype interactions explained only 2.9%. Linkage mapping showed that loci detected in more host genotypes generally explained more phenotypic variance than those detected in fewer host genotypes. At some loci, genetic variation correlated with increased yeast persistence across multiple organs (general loci) while at others increased persistence in one organ came at the cost of decreased persistence in another (antagonistic loci). General loci contributed disproportionately to brain persistence, whereas liver persistence reflected contributions from both classes. The clinical parent showed greater persistence than the laboratory parent in every host-organ combination, and the additive effects of detected loci predicted the direction of this advantage. Overall, this work shows that in this system, relative microbial persistence is polygenic, with a strong additive component and only a very small contribution from microbial genotype-by-host genotype interactions.

Explore related subjects

geneticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ehrenreich, I. M., Bernardo, B., Eoh, Y., Dean, M. D.. 2026-11-09. A largely shared genetic architecture underlies Saccharomyces cerevisiae persistence across different mouse host genotypes. https://doi.org/10.64898/2026.11.04.764303

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Host control and regulation of human anellovirus persistence

Anelloviruses are the most abundant and diverse eukaryotic viruses known to infect humans and can persist throughout our lifetimes. Despite their ubiquity, the host factors governing their physiologic distribution and abundance remain poorly understood. Here, we construct a viral pangenome of 2,023 strains to quantify anellovirus DNA in >1.1 million participants spanning three genetic biobanks. Genome-wide association studies identify 121 loci linked to viral persistence, predominantly via immune regulation by NF-kB signaling. Further, we associate variable anellovirus detection with conditions characterized by immune dysfunction, including lymphoid malignancies. By screening 3.2 petabases of human single-cell sequencing data, we identify myeloid progenitors in the bone marrow as a prominent site of anellovirus transcription in vivo. Finally, Perturb-seq of anellovirus proteins reveals that anellovirus ORF2, particularly from Alphatorquevirus, attenuates TNF-a-induced NF-kB signaling, connecting host genetic variation, cellular context, and viral immunomodulation to characterize the persistence of the eukaryotic human virome's most abundant component.

genetics↗
bioRxiv2026

Regulation of sociality and neuronal development by the translation initiation factor eIF4H1 in Drosophila

Most animal species exhibit some level of sociality. However, whether sociality-related traits evolved independently, or are instead derived from common core mechanisms, remains controversial. Nevertheless, an emerging theoretical framework stipulates that key aspects of how animals interact with their social environments may be regulated by a phylogenetically conserved genetic toolkit. Therefore, we hypothesized that mutations that lead to social deficits in specific human disorders may implicate genes that play conserved roles in the regulation of core social traits across Animalia. Specifically, here we focus on genes associated with Williams syndrome (WS), a rare human multi-system disorder characterized in part by hypersocial cognitive traits. WS is caused by a hemizygous chromosomal microdeletion of 25-28 protein-coding genes. Consequently, it has been hypothesized that haploinsufficiency in at least one of these genes plays an important role in the development and/or function of social neural circuits in humans. Because the Drosophila genome encodes orthologs of 17 of the 28 genes deleted in WS, we reasoned that at least some of them may serve a conserved role in the regulation of social traits across flies and humans, as predicted by the genetic toolkit framework. Using a neuron-specific RNAi knockdown screen, we identified eIF4H1, an ortholog of a highly conserved subunit of the eukaryotic translation initiation complex eIF4F, as a candidate gene for neuronal regulation of sociality in the fly. We show that eIF4H1 expression is predominantly neuronal in the adult fly brain, and that its action plays a differential role in the organization of specific dopaminergic neuron subtypes that are associated with sociality and cognitive functions. These results indicate that eIF4H1 may serve a conserved function in regulating the development of the neuronal circuits that regulate social behaviors, thus supporting the idea of a conserved sociality genetic toolkit.

genetics↗
bioRxiv2026

Genomic signatures of long-term selection in the Langhill dairy herd: the power of a five-decade experiment for sustainable dairy cattle breeding

Background Selective breeding has transformed dairy cattle productivity, but the genomic consequences of long-term directional selection - what it costs in diversity and where in the genome it acts - are hard to quantify because contemporaneous control populations are rare. The Langhill experiment, established in 1973, is one of the world's longest-running dairy cattle selection trials with a designed control line kept under common management. We used this resource population to ask what five decades of bull selection have cost in genetic diversity, where in the genome selection has acted, and whether complementary scans converge on the loci under selection. Results We genotyped archived blood samples from 1,126 cows of two genetic lines: a Select line sired by bulls in the top decile of UK genetic merit for milk fat-plus-protein yield, and a Control line sired by bulls of average merit. The Select line showed the expected gains in every yield trait. Inbreeding accumulated at the same annual rate in both lines, and effective population size, estimated from that rate, was approximately 33. Linkage disequilibrium was higher in the Select line at every marker distance from 2 to 300 kb. Autozygosity was 24.7% higher in the Select line than in the Control line (0.078 versus 0.063), a difference robust across four calling parameter sets and two independent callers. The excess was confined to runs of homozygosity longer than 2 Mb; shorter runs did not differ between lines, confirming a shared founder base and placing all divergence after the lines were split. It did not arise from a numerically narrower sire pool: the Select line used more sires (79 versus 72), each with fewer daughters, yet its cows were three times more related to one another. Twenty-eight regions across thirteen chromosomes showed strong differentiation; intersecting five scans identified a four-method signal on chromosome 21 spanning the SERPINA gene cluster and sixteen three-method regions, including chromosome 3, with haplotype and diversity statistics agreeing on the line carrying the signal in fourteen of seventeen. Autozygosity itself did not localise to any region. Conclusions Selection left two genomic footprints: diffuse, recent inbreeding accumulated through the narrow ancestry of the elite sire pool, and localised differentiation at specific loci. Runs of homozygosity index only the first process; the second is captured by frequency- and haplotype-based differentiation scans. Because the cost of inbreeding is incurred through ancestry rather than the number of bulls used, mating schemes that constrain the rate of co-ancestry would be preferable to simply managing the number of sires selected and used.

genetics↗