Evolution of Toxin Resistance in the Grasshopper Mouse: A Comparative Genomics Perspective

Novel traits enable many rodents to thrive in extreme environmental niches. For example, predatory grasshopper mice have co-evolved resistance to painful and lethal neurotoxins produced by their scorpion prey. Interestingly, toxin resistance in the three species of grasshopper mice (Onychomys torridus, Onychomys leucogaster, and Onychomys arenicola) varies; Onychomys torridus exhibits the highest resistance and Onychomys leucogaster the least. Grasshopper mice also feed on pinacate beetles, whose toxic sprays irritate the eyes and nasal tissues of predators. It has been reported that the grasshopper mice have structural and functional modifications in the sodium channel Nav1.8 that decrease the effect of the toxins. This raises interesting questions: What are the molecular adaptations underlying toxin resistance in Onychomys? What genes contribute to pain and toxin response? Which sodium and potassium channels are involved? To address these questions, I followed a comparative genomics approach. I produced the first high-quality reference genomes and annotations for Onychomys species and Peromyscus eremicus (a closely related outgroup). I implemented a comprehensive pipeline to detect positive selection across genome-scale datasets and identified a promising candidate gene for pain resistance in Onychomys: Nav1.3 (Scn3a). This sodium channel gene is expressed in the central nervous system and plays an important role in nociceptive signalling. I also detected that in O. torridus, the Foxe3 gene is positively selected, which is involved in the formation and maintenance of the eye lens. Given that their eyes are continuously exposed to toxins, selection on this gene may contribute to enhanced protection or repair of eye tissue. Additionally, I detected an Onychomys-specific tandem gene duplication of the Cblif gene, which encodes a glycoprotein crucial for vitamin B12 absorption. This adaptation likely supports the species' dietary specialisation and modified stomach morphology, where parietal cells expressing Cblif are especially numerous. To better understand the molecular response to toxin exposure, we generated RNA-Seq data from the dorsal root ganglion and the trigeminal ganglion from mice that have been exposed to toxic sprays from pinacate beetles. I observed the upregulation of genes associated with transportation processes in O. torridus that can be linked to toxin resistance. In conclusion, our findings provide a key step for establishing the Onychomys species as a model system for studying toxin resistance, pain response, and behavioural traits.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2025

Author dc:creator

• Pérez Calles, Claudia

Advisor dc:contributor.advisor

• Keane, Thomas

• Onychomys torridus
• comparative genomics
• pangenome
• mouse genomes
• genomic variation
• Peromyscus eremicus

Licence

• https://www.repository.cam.ac.uk/bitstreams/6c7d2031-09f0-46e9-b9f8-7d864d474f6a/download
• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.125038

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/395589