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Journal Article Ppublish 14 citations

PubMed: 38147547 DOI: 10.1073/pnas.2313210120

Genetic crosses within and between species of .

Proc Natl Acad Sci U S A 121(1):e2313210120

Authors: Sebastian Shaw, Ian S Cohn, Rodrigo P Baptista, Guoqin Xia, Bruno Melillo, Fiifi Agyabeng-Dadzie, Jessica C Kissinger, Boris Striepen

Affiliations

  • Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030.
  • Department of Chemistry, Scripps Research, La Jolla, CA 92037.
  • Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142.
  • Department of Genetics, University of Georgia, Athens, GA 30602.
  • Center for Tropical and Emerging Global Diseases and Institute of Bioinformatics, University of Georgia, Athens, GA 30602.

Abstract

Parasites and their hosts are engaged in reciprocal coevolution that balances competing mechanisms of virulence, resistance, and evasion. This often leads to host specificity, but genomic reassortment between different strains can enable parasites to jump host barriers and conquer new niches. In the apicomplexan parasite , genetic exchange has been hypothesized to play a prominent role in adaptation to humans. The sexual lifecycle of the parasite provides a potential mechanism for such exchange; however, the boundaries of sex are currently undefined. To explore this experimentally, we established a model for genetic crosses. Drug resistance was engineered using a mutated phenylalanyl tRNA synthetase gene and marking strains with this and the previously used Neo transgene enabled selection of recombinant progeny. This is highly efficient, and genomic recombination is evident and can be continuously monitored in real time by drug resistance, flow cytometry, and PCR mapping. Using this approach, multiple loci can now be modified with ease. We demonstrate that essential genes can be ablated by crossing a Cre recombinase driver strain with floxed strains. We further find that genetic crosses are also feasible between species. Crossing a parasite of cattle and humans, and a mouse parasite resulted in progeny with a recombinant genome derived from both species that continues to vigorously replicate sexually. These experiments have important fundamental and translational implications for the evolution of and open the door to reverse- and forward-genetic analysis of parasite biology and host specificity.

MeSH

Genes, Host Specificity, Sex, Parasites, Crosses, Genetic

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