Biology subjects

Schaye, E. S.

Publications and source records attributed to Schaye, E. S..

3 recordsLinked to original sources

bioRxiv2025

Caenorhabditis briggsae ancestral genomic hyper-diversity contrasts with globally distributed genome-wide haplotypes

Comparative genomics provides a powerful framework to uncover the molecular and evolutionary mechanisms that shape genetic diversity within and across species, revealing how shared and lineage-specific processes influence their evolutionary trajectories through time. The nematode Caenorhabditis briggsae is distributed world-wide and is a comparative model to Caenorhabditis elegans in the biology of development, cellular mechanisms, neurobiology, genetic mappings of complex traits, and genome evolution. Following massive collection efforts by the nematode research community, we present the isolation of over 2,000 wild strains and analyses of genome sequences that catalog over six million single-nucleotide and insertion-deletion variants. This genome and strain resource provide a powerful means to interrogate the causal genetic bases of phenotypic variation for diverse traits. Additionally, we describe its global population structure and discover new and genetically distinct groups within this primarily self-fertilizing species, including groups of highly related strains that were sampled across different continents. We leverage expansive genetic variation to decipher the effects of linkage and selection on the distribution of genetic diversity across the genome and across geographic regions. Within the species, we find genomic regions with extremely high levels of genetic variation similar to hyper-divergent regions found in C. elegans and other species. These regions harbor new genes and variation enriched for environmental sensing and pathogen responses. In comparison to the outbreeding sister species Caenorhabditis nigoni, we conclude that long-term balancing selection has maintained substantial functional variation since the divergence from their outbreeding ancestor, likely in response to differences in the ecological niche. Overall, this massive strain resource enables future comparative genetics and genomics studies, including genome-wide association studies between Caenorhabditis species.

genomics↗

bioRxiv2025

Survey of benzimidazole resistance in ascarid parasites of poultry

Ascarid parasites, such as Ascaridia galli and Heterakis gallinarum, are nearly ubiquitous in poultry and can cause serious production losses. H. gallinarum is of particular concern because of its role as a vector for the protozoan Histomonas meleagridis, the cause of blackhead disease. Currently, only the benzimidazole anthelmintic, fenbendazole (FBZ), is approved for use in poultry, and recently, FBZ resistance has been discovered and validated in populations of the turkey ascarid Ascaridia dissimilis and in ascarid of gallinaceous birds H. gallinarum. Here, we further explore the prevalence of resistance in poultry ascarids by testing FBZ efficacy against thirteen isolates of A. galli and eight isolates of H. gallinarum. Isolates were used to infect day-old naive chickens. Four weeks after infection, animals to be treated received the label-recommended dosage of FBZ (SafeGuard Aquasol) for five days, per the manufacturers directions. One week after the fifth day of treatment, animals were euthanized and parasite burdens were counted to determine treatment efficacy between the untreated and treated groups. Resistance was identified and validated in a single isolate of A. galli, marking the first confirmed case in the species. All isolates of H. gallinarum were found to be resistant. The emergence of resistance in A. galli and the high prevalence of resistance in H. gallinarum highlight the growing concern of resistance in parasites of poultry. Without approved alternative treatments, the detrimental effects of infections cannot be mitigated in resistant populations, significantly impacting profit margins. Diagnostics that enable broader surveys are necessary to understand the full scope of the problem. However, we show that resistance is present across production species and should act as an impetus for the discovery of new treatments and the adoption of new management strategies.

microbiology↗

bioRxiv2024

Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans

Albendazole and ivermectin are the two most commonly co-administered anthelmintic drugs in mass-drug administration programs worldwide. Despite emerging resistance, we do not fully understand the mechanisms of resistance to these drugs nor the consequences of delivering them in combination. Albendazole resistance has primarily been attributed to variation in the drug target, a beta-tubulin gene. Ivermectin targets glutamate-gated chloride channel (GluCl) genes, but it is unknown whether these genes are involved in ivermectin resistance in nature. Using Caenorhabditis elegans, we defined the fitness costs associated with loss of the drug target genes singly or in combinations of the genes that encode GluCl subunits. We quantified the loss-of-function effects on three traits: (i) multi-generational competitive fitness, (ii) fecundity, and (iii) development. In competitive fitness and development assays, we found that a deletion of the beta-tubulin gene ben-1 conferred albendazole resistance, but ivermectin resistance required loss of two GluCl genes (avr-14 and avr-15) or loss of three GluCl genes (avr-14, avr-15, and glc-1). The fecundity assays revealed that loss of ben-1 did not provide any fitness benefit in albendazole and that no GluCl deletion mutants were resistant to ivermectin. Next, we searched for evidence of multi-drug resistance across the three traits. Loss of ben-1 did not confer resistance to ivermectin, nor did loss of any single GluCl subunit or combination confer resistance to albendazole. Finally, we assessed the development of 124 C. elegans wild strains across six benzimidazoles and seven macrocyclic lactones to identify evidence of multi-drug resistance between the two drug classes and found a strong phenotypic correlation within a drug class but not across drug classes. Because each gene affects various aspects of nematode physiology, these results suggest that it is necessary to assess multiple fitness traits to evaluate how each gene contributes to anthelmintic resistance. AUTHOR SUMMARYControl of parasitic nematodes often depends on mass-drug administration (MDA) programs, where combinations of anthelmintics are distributed to at-risk populations. Two commonly co-administered anthelmintic drugs in MDA programs are albendazole and ivermectin, and resistance to both drugs has emerged. Although the mechanism of resistance (MoR) to albendazole has been primarily attributed to variation in a beta-tubulin gene, the MoR to ivermectin remains unknown. Ivermectin acts through pentameric glutamate-gated chloride channels (GluCls). However, it is unclear whether genes that encode GluCls are involved in ivermectin resistance in parasitic nematodes. Using Caenorhabditis elegans, we quantified the fitness costs associated with deletions of the beta-tubulin gene ben-1 and three genes encoding GluCl subunits avr-14, avr-15, and glc-1 on three traits: (i) multi-generational competitive fitness, (ii) fecundity, and (iii) development. We found different anthelmintic responses across strains and traits but no evidence of multi-drug resistance. Our results suggest that multiple traits should be considered to understand resistance comprehensively and that the determination of whether a gene plays a role in anthelmintic resistance depends on the trait measured. Understanding the quantitative effects and fitness-associated costs of each GluCl subunit in C. elegans can help explain the costs of mutations in these subunits in parasites.

genetics↗