Genetic breakdown of a Tet-off conditional lethality system for insect population control

Abstract

Genetically modified conditional lethal strains have been created to improve the control of insect pest populations damaging to human health and agriculture. However, understanding the potential for the genetic breakdown of lethality systems by rare spontaneous mutations, or selection for inherent suppressors, is critical since field release studies are in progress. This knowledge gap was addressed in a Drosophila tetracycline-suppressible embryonic lethality system by analyzing the frequency and structure of primary-site spontaneous mutations and second-site suppressors resulting in heritable survivors from 1.2 million zygotes. Here we report that F 1 survivors due to primary-site deletions and indels occur at a 5.8 × 10 −6 frequency, while survival due to second-site maternal-effect suppressors occur at a~10 −5 frequency. Survivors due to inherent lethal effector suppressors could result in a resistant field population, and we suggest that this risk may be mitigated by the use of dual redundant, albeit functionally unrelated, lethality systems.

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

“…We discuss and demonstrate methods to mitigate some of these resistance mechanisms in previous publications ( Maselko et al, 2017 ; Maselko et al, 2020 ). Recently, published work describes instances where such resistance mutations can arise reproducibly at very low frequencies ( Zhao et al, 2020 ).…”

A transgenic female killing system for the genetic control of Drosophila suzukii

“…However, the decision of releasing fertile strains should be carefully evaluated since the resistance to the lethality systems could arise. Recent studies showed that spontaneous mutations in a genetic strain could lead to the buildup of revertants, and in addition, a pre-existing inherent variation in the targeted field population could suppress the lethal system of an effector gene 47 , 48 . Nevertheless, FK approach can be used to produce male-only population and prevent the collateral damage to the fruits compared to a bi-sexual release, in which females can still damage fruits and lead to subsequent infestations even if they are sterilized 49 , 50 .…”

Reprogramming the Metabolic Network in Kluyveromyces lactis with a Transcriptional Switch for De Novo Lacto-N-biose Synthesis

“…The transcriptional switch is a useful technology in regulating the expression of target genes, especially essential genes. The most popular transcriptional switches are tet-off, , phl-off, cym-off, cam-off, , etc. In this study, we designed an Agm1-on/off switch based on the cam-off system to regulate the expression level of the AGM1 gene and attempted reprogramming the metabolic network in K.…”