Site-specific selfish genes as tools for the control and genetic engineering of natural populations

Abstract

Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can be used to manipulate natural populations, even if the number of individuals released is a small fraction of the entire population. For example, a genetic load sufficient to eradicate a population can be imposed in fewer than 20 generations, if the target is an essential host gene, the knockout is recessive and the selfish gene has an appropriate promoter. There will be selection for resistance, but several strategies are available for reducing the likelihood of it evolving. These genes may also be used to genetically engineer natural populations, by means of population-wide gene knockouts, gene replacements and genetic transformations. By targeting sexlinked loci just prior to meiosis one may skew the population sex ratio, and by changing the promoter one may limit the spread of the gene to neighbouring populations. The proposed constructs are evolutionarily stable in the face of the mutations most likely to arise during their spread, and strategies are also available for reversing the manipulations.

Genetics‐based methods for agricultural insect pest management

“…These gene‐editing approaches have been developed in mosquitoes either to suppress vector populations, by affecting female fertility (Burt, 2003; Deredec et al ., 2008; Hammond et al ., 2016), or to modify a population, by spreading a trait that affects the ability to harbour pathogens (Gantz et al ., 2015). Gene‐editing approaches could also be used to suppress agricultural pests and/or manage resistance; for example, CRISPR gene editing has been used in a functional study to identify suitable gene targets in diamondback moth (Huang et al ., 2016).…”

Agricultural production: assessment of the potential use of Cas9-mediated gene drive systems for agricultural pest control

“…If the maximal rate of increase of the drive in a DBM field population was 5-fold per generation, then such a gene drive could be effective. Burt (2003) and others (Deredec, Burt, and Godfray 2008) outline additional gene drive systems that could be even more efficient and would be theoretically predicted to limit even tropical populations of DBM.…”

“…Modeling suggests that it would be advantageous to target genes that are essential for females but not males, or required for germ-cell development or reproduction in one sex (Burt 2003;Deredec, Burt, and Godfray 2008). One possibility would be to target the transformer (tra) gene, which is essential for female development in screwworm, as in most Diptera (Li et al 2013).…”

“…Riggin-Bucci and Gould 1997). Burt (2003) has shown theoretically that a meiosis-based, gene-drive system with 90% efficiency could reduce survival by 80%. If the maximal rate of increase of the drive in a DBM field population was 5-fold per generation, then such a gene drive could be effective.…”

Genome-Editing Technologies: Principles and Applications

“…Finally, targeted nucleases have also been used to inactivate pathogenic genes to prevent viral (Lin et al 2014) or parasitic (Ghorbal et al 2014) infection, as well as to introduce knockin-specific factors capable of imparting pathogen resistance . Intriguingly, targeted nucleases could also serve as conduits for curbing mosquito-or insect-borne diseases through a technique known as gene drive (Burt 2003;Sinkins and Gould 2006), which harnesses genome editing to facilitate the introduction of a specific gene or mutation that can then confer a particular phenotype into a host and also be transmitted to its progeny (Windbichler et al 2011). Gene drives have now been tested in the malaria vector mosquitos Anopheles stephensi and Anopheles gambiae (Hammond et al 2016) as a means for achieving population control and to prevent disease transmission, respectively.…”