Abstract
The persistence of transgenes in the environment is a consideration in risk assessments of transgenic organisms. Combining mathematical models that predict the frequency of transgenes and experimental demonstrations can validate the model predictions, or can detect significant biological deviations that were neither apparent nor included as model parameters. In order to assess the correlation between predictions and observations, models were constructed to estimate the frequency of a transgene causing male sexual sterility in simulated populations of a malaria mosquito Anopheles gambiae that were seeded with transgenic females at various proportions. Concurrently, overlapping-generation laboratory populations similar to those being modeled were initialized with various starting transgene proportions, and the subsequent proportions of transgenic individuals in populations were determined weekly until the transgene disappeared. The specific transgene being tested contained a homing endonuclease gene expressed in testes, I-PpoI, that cleaves the ribosomal DNA and results in complete male sexual sterility with no effect on female fertility. The transgene was observed to disappear more rapidly than the model predicted in all cases. The period before ovipositions that contained no transgenic progeny ranged from as little as three weeks after cage initiation to as long as 11 weeks.
Highlights
The persistence of a transgene in populations of genetically modified organisms in the environment is an important consideration in determining its risk [1,2], persistence is not, in itself, an indication of harm, which would be a consideration in risk assessment
We modelled, using stochastic simulations, and in parallel, measured in laboratory experiments, the proportion of individuals carrying a transgene that causes complete sexual sterility in male hemizygotes
The number of GM and WT females and males that were restocked in cages of Ag(DSM)1 at three initial proportions of females (Figure 3) and the three trials of Ag(DSM)2 at two initial proportions (Figure 4)
Summary
The persistence of a transgene in populations of genetically modified organisms in the environment is an important consideration in determining its risk [1,2], persistence is not, in itself, an indication of harm, which would be a consideration in risk assessment. Heritable factors (including transgenes) that spread and persist can be desirable for prolonged disease suppression [8,9,10], and these qualities are traits of particular types of transgenes that are currently being created [11,12]. For those conferring sexual sterility [13] or larval lethality conferred by systems such as RIDLTM [14], persistence is neither intended nor expected, due to the phenotype of the transgene. An incremental step-by-step process of developing self-limiting approaches prior to persistent transgenes is recommended for development of genetically-modified mosquitoes [2], in part so that predictive tools can be devised and tested experimentally to ensure that the modified-mosquito behaviors expected occur or, if deviations from the models occur, whether these present greater risk than what was expected prior to the observations
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