Applications and status of gene drive in plants
Applications and status of gene drive in plants
Tags: Ecology, Fruit fly, Invasive species, Population genetics/dynamics, Toxin-antidoteHay BA, PLOS Biology, 23. 2025.
Globalization—the movement of humans, plants, animals, and microbes—together with climate change, place numerous plant and animal species under novel stresses. For plants, threats include global warming, invasive species, weeds, animal pests, and vectors of disease. Harms can be mitigated or prevented through population-scale genetic alterations that introduce beneficial traits such as disease resistance or drought tolerance (population modification), or that eliminate a harmful population (population suppression). Gene drive is a possible tool for achieving these goals. DNA mediating gene drive comprises one or more genes (the drive element) that promote their own inheritance—and any linked cargo—at rates exceeding (>50%) those of other genes. This can lead to an increase in drive element frequency even if its presence results in a fitness cost to carriers. Gene drive is attractive because it is self-amplifying and self-sustaining.
One class of gene drive utilizes a Toxin-Antidote (TA) element. In nature, these often consist of two tightly linked protein-encoding genes. One encodes a toxin that is inherited by all gametes and/or progeny of a carrier; the second is an antidote that protects carriers from death. The TA element-bearing chromosome gains a relative transmission advantage by causing death of those who fail to inherit it. The first synthetic gene drive was engineered using TA logic, in Drosophila melanogaster in 2007. Recently, TA logic was also used to create the first synthetic gene drive elements in plants, in Arabidopsis thaliana. These use a Cleave and Rescue mechanism (ClvR) adapted from earlier work in Drosophila. ClvR uses DNA cleavage mediated by Cas9 and guide RNAs (gRNAs), followed by inaccurate repair, to create loss-of-function (LOF) alleles (the toxin) of endogenous versions of an essential gene. ClvR also includes a Rescue version of the essential gene recoded to prevent gene disruption (the antidote), which guarantees survival of carriers. In Drosophila, ClvR spreads because LOF alleles created in parents cause the death of progeny who lack essential gene function. In Arabidopsis this strategy was used to create gamete killers. A naturally occurring male gamete killer from rice, DUYAO-JIEYAO, consists of a two-gene protein–protein TA cassette. Modeling suggests that gamete killers such as these can bring about population modification or suppression. Interestingly, the DUYAO-JIEYAO element has undergone a substantial increase in frequency in Japonica rice populations in China over the last 50 years, demonstrating the power of such elements in nature.
