GEPHE SUMMARY Print
Gephebase Gene
Entry Status
Published
GepheID
GP00001851
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
sensitive
Trait State in Taxon B
resistant
Ancestral State
Taxon A
Taxonomic Status
Taxon A
Common Name
-
Synonyms
roundworm; Rhabditis elegans; Caenorhabditis elegans (Maupas, 1900); Rhabditis elegans Maupas, 1900
Rank
species
Lineage
Show more ... s; Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Protostomia; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
-
Synonyms
roundworm; Rhabditis elegans; Caenorhabditis elegans (Maupas, 1900); Rhabditis elegans Maupas, 1900
Rank
species
Lineage
Show more ... s; Eukaryota; Opisthokonta; Metazoa; Eumetazoa; Bilateria; Protostomia; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis
NCBI Taxonomy ID
is Taxon B an Infraspecies?
Yes
Taxon B Description
ED3005, JU1808, MY18, MY795
GENOTYPIC CHANGE
Presumptive Null
Yes
Molecular Type
Aberration Type
Deletion Size
-
Molecular Details of the Mutation
Del_3540407_3540408 – 1bp deletion in coding exon 2
Experimental Evidence
Authors
Hahnel SR; Zdraljevic S; Rodriguez BC; Zhao Y; McGrath PT; Andersen EC
Abstract
Benzimidazoles (BZ) are essential components of the limited chemotherapeutic arsenal available to control the global burden of parasitic nematodes. The emerging threat of BZ resistance among multiple nematode species necessitates the development of novel strategies to identify genetic and molecular mechanisms underlying this resistance. All detection of parasitic helminth resistance to BZ is focused on the genotyping of three variant sites in the orthologs of the β-tubulin gene found to confer resistance in the free-living nematode Caenorhabditis elegans. Because of the limitations of laboratory and field experiments in parasitic nematodes, it is difficult to look beyond these three sites to identify additional mechanisms that might contribute to BZ resistance in the field. Here, we took an unbiased genome-wide mapping approach in the free-living nematode species C. elegans to identify the genetic underpinnings of natural resistance to the commonly used BZ, albendazole (ABZ). We found a wide range of natural variation in ABZ resistance in natural C. elegans populations. In agreement with known mechanisms of BZ resistance in parasites, we found that a majority of the variation in ABZ resistance among wild C. elegans strains is caused by variation in the β-tubulin gene ben-1. This result shows empirically that resistance to ABZ naturally exists and segregates within the C. elegans population, suggesting that selection in natural niches could enrich for resistant alleles. We identified 25 distinct ben-1 alleles that are segregating at low frequencies within the C. elegans population, including many novel molecular variants. Population genetic analyses indicate that ben-1 variation arose multiple times during the evolutionary history of C. elegans and provide evidence that these alleles likely occurred recently because of local selective pressures. Additionally, we find purifying selection at all five β-tubulin genes, despite predicted loss-of-function variants in ben-1, indicating that BZ resistance in natural niches is a stronger selective pressure than loss of one β-tubulin gene. Furthermore, we used genome-editing to show that the most common parasitic nematode β-tubulin allele that confers BZ resistance, F200Y, confers resistance in C. elegans. Importantly, we identified a novel genomic region that is correlated with ABZ resistance in the C. elegans population but independent of ben-1 and the other β-tubulin loci, suggesting that there are multiple mechanisms underlying BZ resistance. Taken together, our results establish a population-level resource of nematode natural diversity as an important model for the study of mechanisms that give rise to BZ resistance.
Additional References
RELATED GEPHE
Related Genes
Related Haplotypes
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