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Tanny, R. E.

Publications and source records attributed to Tanny, R. E..

3 recordsLinked to original sources

Deep sampling of Hawaiian Caenorhabditis elegans reveals high genetic diversity and admixture with global populations

Recent efforts to understand the natural niche of the keystone model organism Caenorhabditis elegans have suggested that this species is cosmopolitan and associated with rotting vegetation and fruits. However, most of the strains isolated from nature have low genetic diversity likely because recent chromosome-scale selective sweeps contain alleles that increase fitness in human-associated habitats. Strains from the Hawaii Islands are highly divergent from non-Hawaiian strains. This result suggests that Hawaiian strains might contain ancestral genetic diversity that was purged from most non-Hawaiian strains by the selective sweeps. To characterize the genetic diversity and niche of Hawaiian C. elegans, we sampled across the Hawaiian Islands and isolated 100 new C. elegans strains. We found that C. elegans strains are not associated with any one substrate but are found in cooler climates at high elevations. These Hawaiian strains are highly diverged compared to the rest of the global population. Admixture analysis identified 11 global populations, four of which are from Hawaii. Surprisingly, one of the Hawaiian populations shares recent ancestry with non-Hawaiian populations, including portions of globally swept haplotypes. This discovery provides the first evidence of gene flow between Hawaiian and non-Hawaiian populations. Most importantly, the high levels of diversity observed in Hawaiian strains might represent the complex patterns of ancestral genetic diversity in the C. elegans species before human influence.

ecology

Population selection and sequencing of C. elegans wild isolates identifies a region on chromosome III affecting starvation resistance

To understand the genetic basis of complex traits, it is important to be able to efficiently phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have been isolated from diverse populations around the globe and whole-genome sequenced. As a result, hundreds of wild strains with known genome sequences can be used for genome-wide association studies (GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans starvation resistance has not been characterized, and precise measurement of the trait is time-intensive. Here, we developed a population selection and sequencing-based approach to phenotype starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing (RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that increased in frequency over time are starvation-resistant relative to strains that decreased in frequency. These results document natural variation in starvation resistance. Further, we found that variation in starvation resistance is significantly associated with variation at a region on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for starvation resistance. This study demonstrates the feasibility of using population selection and sequencing in an animal model for phenotypic analyses of quantitative traits, reveals natural variation of starvation resistance in C. elegans, and identifies a genomic region that contributes to such variation.

genetics

A nematode-specific gene underlies bleomycin-response variation in Caenorhabditis elegans

Bleomycin is a powerful chemotherapeutic drug used to treat a variety of cancers. However, individual patients vary in their responses to bleomycin. The identification of genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic determinants of bleomycin-response differences by performing linkage mapping on recombinants derived from a cross between the laboratory strain (N2) and a wild strain (CB4856). This approach identified a small genomic region on chromosome V that underlies bleomycin-response variation. Using near-isogenic lines and strains with CRISPR-Cas9 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes variation in bleomycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause differences in the potential stress-response function of scb-1 between the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance.

genetics