Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: A modeling study

PLoS Genet. 2023 Jan 23;19(1):e1010591. doi: 10.1371/journal.pgen.1010591. eCollection 2023 Jan.

Abstract

Wolbachia are maternally-inherited bacteria, which can spread rapidly in populations by manipulating reproduction. cifA and cifB are genes found in Wolbachia phage that are responsible for cytoplasmic incompatibility, the most common type of Wolbachia reproductive interference. In this phenomenon, no viable offspring are produced when a male with both cifA and cifB (or just cifB in some systems) mates with a female lacking cifA. Utilizing this feature, we propose new types of toxin-antidote gene drives that can be constructed with only these two genes in an insect genome, instead of the whole Wolbachia bacteria. By using both mathematical and simulation models, we found that a drive containing cifA and cifB together creates a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence. Our results suggest that these new types of drives based on Wolbachia transgenes are safe and flexible candidates for genetic modification of populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Cytoplasm / genetics
  • Cytoplasm / microbiology
  • Cytosol
  • Female
  • Gene Drive Technology*
  • Genome, Insect
  • Insecta / genetics
  • Insecta / microbiology
  • Male
  • Reproduction / genetics
  • Symbiont Induced Cytoplasmic Incompatibility*
  • Symbiosis
  • Transgenes
  • Wolbachia* / genetics

Grants and funding

This study was supported by laboratory startup funds from Peking University and the SLS-Qidong Innovation Fund to JC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.