The publication of the Caenorhabditis briggsae reference genome in 2003 enabled the first comparative genomics studies between C. elegans and C. briggsae, shedding light on the evolution of genome content and structure in the Caenorhabditis genus. However, despite being widely used, the currently available C. briggsae reference genome is substantially less complete and structurally accurate than the C. elegans reference genome. Here, we used high-coverage Oxford Nanopore long-read and chromosome conformation capture data to generate chromosome-level reference genomes for two C. briggsae strains: QX1410, a new reference strain closely related to the laboratory AF16 strain, and VX34, a highly divergent strain isolated in China. We also sequenced 99 recombinant inbred lines (RILs) generated from reciprocal crosses between QX1410 and VX34 to create a recombination map and identify chromosomal domains. Additionally, we used both short- and long-read RNA sequencing (RNA-seq) data to generate high-quality gene annotations. By comparing these new reference genomes to the current reference, we reveal that hyper-divergent haplotypes cover large portions of the C. briggsae genome, similar to recent reports in C. elegans and C. tropicalis. We also show that the genomes of selfing Caenorhabditis species have undergone more rearrangement than their outcrossing relatives, which has biased previous estimates of rearrangement rate in Caenorhabditis. These new genomes provide a substantially improved platform for comparative genomics in Caenorhabditis and narrow the gap between the quality of genomic resources available for C. elegans and C. briggsae.

Parasitic nematode infections cause an enormous global burden to both human and livestock populations. Resistance to the limited arsenal of anthelmintic drugs used to combat these infections is widespread, including resistance to benzimidazole (BZ) compounds commonly found in livestock parasites. Previous studies using the free-living nematode Caenorhabditis elegans to model parasitic nematode resistance have shown that loss-of-function mutations in the beta-tubulin gene ben-1 confer resistance to BZ drugs. However, the mechanism of resistance and the tissue-specific susceptibility are not well known in any nematode species. To identify in which tissue(s) ben-1 function underlies BZ susceptibility, transgenic strains that express ben-1 in different tissues, including hypodermis, muscles, neurons, intestine, and ubiquitous expression were generated. High-throughput fitness assays were performed to measure and compare the quantitative responses to BZ compounds among different transgenic lines. Significant BZ susceptibility was observed in animals expressing ben-1 in neurons, comparable to expression using the ben-1 promoter. This result suggests that ben-1 function in neurons underlies susceptibility to BZ. Subsetting neuronal expression of ben-1 based on neurotransmitter system further restricted ben-1 function in cholinergic neurons to cause BZ susceptibility. These results better inform our current understanding of the cellular mode of action of BZ and also suggest additional treatments that might potentiate the effects of BZs.

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The publication of the Caenorhabditis briggsae reference genome in 2003 enabled the first comparative genomics studies between C. elegans and C. briggsae, shedding light on the evolution of genome content and structure in the Caenorhabditis genus. However, despite being widely used, the currently available C. briggsae reference genome is substantially less complete and structurally accurate than the C. elegans reference genome. Here, we used high-coverage Oxford Nanopore long-read and chromosome conformation capture data to generate chromosomally resolved reference genomes for two C. briggsae strains: QX1410, a new reference strain closely related to the laboratory AF16 strain, and VX34, a highly divergent strain isolated in China. We also sequenced 99 recombinant inbred lines (RILs) generated from reciprocal crosses between QX1410 and VX34 to create a recombination map and identify chromosomal domains. Additionally, we used both short- and long-read RNA sequencing (RNA-seq) data to generate high-quality gene annotations. By comparing these new reference genomes to the current reference, we reveal that hyper-divergent haplotypes cover large portions of the C. briggsae genome, similar to recent reports in C. elegans and C. tropicalis. We also show that the genomes of selfing Caenorhabditis species have undergone more rearrangement than their outcrossing relatives, which has biased previous estimates of rearrangement rate in Caenorhabditis. These new genomes provide a substantially improved platform for comparative genomics in Caenorhabditis and narrow the gap between the quality of genomic resources available for C. elegans and C. briggsae.

No abstract