scholarly journals From QTL to gene: C. elegans facilitates discoveries of the genetic mechanisms underlying natural variation

2021 ◽  
Author(s):  
Kathryn S. Evans ◽  
Marijke H. van Wijk ◽  
Patrick T. McGrath ◽  
Erik C. Andersen ◽  
Mark G. Sterken
2018 ◽  
Vol 93 (3) ◽  
pp. 319-331 ◽  
Author(s):  
P. Andrus ◽  
R. Rae

AbstractThe genetic mechanisms of how free-living nematodes evolved into parasites are unknown. Current genetic model nematodes (e.g.Caenorhabditis elegans) are not well suited to provide the answer, and mammalian parasites are expensive and logistically difficult to maintain. Here we propose the terrestrial gastropod parasitePhasmarhabditis hermaphroditaas a new alternative to study the evolution of parasitism, and outline the methodology of how to keepP. hermaphroditain the lab for genetic experiments. We show thatP. hermaphrodita(and several otherPhasmarhabditisspecies) are easy to isolate and identify from slugs and snails from around the UK. We outline how to make isogenic lines using ‘semi-natural’ conditions to reduce in-lab evolution, and how to optimize growth using nematode growth media (NGM) agar and naturally isolated bacteria. We show thatP. hermaphroditais amenable to forward genetics and thatuncandsmamutants can be generated using formaldehyde mutagenesis. We also detail the procedures needed to carry out genetic crosses. Furthermore, we show natural variation within ourPhasmarhabditiscollection, with isolates displaying differences in survival when exposed to high temperatures and pH, which facilitates micro and macro evolutionary studies. In summary, we believe that this genetically amenable parasite that shares many attributes withC. elegansas well as being in Clade 5, which contains many animal, plant and arthropod parasites, could be an excellent model to understand the genetic basis of parasitism in the Nematoda.


2021 ◽  
Author(s):  
Janneke Wit ◽  
Steffen R. Hahnel ◽  
Briana C. Rodriguez ◽  
Erik Andersen

Treatment of parasitic nematode infections depends primarily on the use of anthelmintics. However, this drug arsenal is limited, and resistance against most anthelmintics is widespread. Emodepside is a new anthelmintic drug effective against gastrointestinal and filarial nematodes. Nematodes that are resistant to other anthelmintic drug classes are susceptible to emodepside, indicating that the emodepside mode of action is distinct from previous anthelmintics. The laboratory-adapted Caenorhabditis elegans strain N2 is sensitive to emodepside, and genetic selection and in vitro experiments implicated slo-1, a BK potassium channel gene, in emodepside mode of action. In an effort to understand how natural populations will respond to emodepside, we measured brood sizes and developmental rates of wild C. elegans strains after exposure to the drug and found natural variation across the species. Some variation in emodepside responses can be explained by natural differences in slo-1. This result suggests that other genes in addition to slo-1 underlie emodepside resistance in wild C. elegans strains. Additionally, all assayed strains have higher offspring production in low concentrations of emodepside (a hormetic effect), which could impact treatment strategies. We find that natural variation affects emodepside sensitivity, supporting the suitability of C. elegans as a model system to study emodepside responses across parasitic nematodes.


PLoS Genetics ◽  
2020 ◽  
Vol 16 (8) ◽  
pp. e1008984
Author(s):  
Huimin Na ◽  
Stefan Zdraljevic ◽  
Robyn E. Tanny ◽  
Albertha J. M. Walhout ◽  
Erik C. Andersen

Nematology ◽  
2017 ◽  
Vol 19 (4) ◽  
pp. 375-387 ◽  
Author(s):  
Robbie Rae

The evolutionary genetic mechanisms that are responsible for the transition of free-living nematodes to parasites are unknown and current nematode models used to study this have limitations. The gastropod parasitePhasmarhabditis hermaphroditacould be used as a new model to dissect the molecular mechanisms involved in the evolution of parasitism.Phasmarhabditis hermaphroditais a facultative parasite of slugs and snails that, likeCaenorhabditis elegansandPristionchus pacificus, can also be maintained easily under laboratory conditions.Phasmarhabditis hermaphroditaandPhasmarhabditisspecies are easy to isolate from the wild and have been found around the world. The phylogenetic position ofPhasmarhabditisis ideal for genomic comparison with other clade 9 species such asC. elegansandP. pacificus, as well as mammalian and insect parasites. These attributes could makeP. hermaphroditaan excellent choice of model to study the evolutionary emergence of parasitism.


Science ◽  
2012 ◽  
Vol 335 (6068) ◽  
pp. 574-578 ◽  
Author(s):  
R. Ghosh ◽  
E. C. Andersen ◽  
J. A. Shapiro ◽  
J. P. Gerke ◽  
L. Kruglyak

2015 ◽  
Vol 25 (20) ◽  
pp. 2730-2737 ◽  
Author(s):  
Luke M. Noble ◽  
Audrey S. Chang ◽  
Daniel McNelis ◽  
Max Kramer ◽  
Mimi Yen ◽  
...  

2018 ◽  
Vol 10 (9) ◽  
pp. 539-548 ◽  
Author(s):  
Ivan de Carlos Cáceres ◽  
Daniel A. Porto ◽  
Ivan Gallotta ◽  
Pamela Santonicola ◽  
Josue Rodríguez-Cordero ◽  
...  

A fully automated high-throughput screen usingC. elegansto investigate genetic mechanisms affecting spinal muscular atrophy (SMA).


2018 ◽  
Author(s):  
Clotilde Gimond ◽  
Anne Vielle ◽  
Nuno Silva-Soares ◽  
Stefan Zdraljevic ◽  
Patrick T. McGrath ◽  
...  

ABSTRACTSperm morphology is critical for sperm competition and thus for reproductive fitness. In the male-hermaphrodite nematode Caenorhabditis elegans, sperm size is a key feature of sperm competitive ability. Yet despite extensive research, the molecular mechanisms regulating C. elegans sperm size and the genetic basis underlying its natural variation remain unknown. Examining 97 genetically distinct C. elegans strains, we observe significant heritable variation in male sperm size but genome-wide association mapping did not yield any QTL (Quantitative Trait Loci). While we confirm larger male sperm to consistently outcompete smaller hermaphrodite sperm, we find natural variation in male sperm size to poorly predict male fertility and competitive ability. In addition, although hermaphrodite sperm size also shows significant natural variation, male and hermaphrodite sperm size do not correlate, implying a sex-specific genetic regulation of sperm size. To elucidate the molecular basis of intraspecific sperm size variation, we focused on recently diverged laboratory strains, which evolved extreme sperm size differences. Using mutants and quantitative complementation tests, we demonstrate that variation in the gene nurf-1 – previously shown to underlie the evolution of improved hermaphrodite reproduction – also explains the evolution of reduced male sperm size. This result illustrates how adaptive changes in C. elegans hermaphrodite function can cause the deterioration of a male-specific fitness trait due to a sexually antagonistic variant, representing an example of intralocus sexual conflict with resolution at the molecular level. Our results further provide first insights into the genetic determinants of C. elegans sperm size, pointing at an involvement of the NURF chromatin remodelling complex.


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