A Synthetic Maternal-Effect Selfish Genetic Element Drives Population Replacement in Drosophila

Abstract

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.

Gene Drive: Evolved and Synthetic

“…20,21 Though the underlying molecular mechanisms are not known, this example stimulated the development of a synthetic gene drive construct in Drosophila with the same logic. 22 The construct combined a microRNAbased repressor of myd88 (an important protein normally supplied by the mother into the embryo) with a zygotically expressed myd88 gene that was not affected by the microRNA and supplied the missing protein. As intended, this construct was able to increase in frequency over successive generations in experimental cage populations.…”

“…Many naturally occurring gene drive systems act as if they produce a toxin and antidote, though often the molecular details are not known. For example, in mice heterozygous for the t -haplotype, and Drosophila heterozygous for Segregation Distorter , these elements somehow act during spermatogenesis to sabotage spermatids or sperm carrying the wild-type allele, with the result that each is transmitted to over 90% of the progeny (compared to the Mendelian 50%). , In Tribolium flour beetles, the medea gene acts in heterozygous females to somehow cause progeny that do not inherit the medea gene to die. , Though the underlying molecular mechanisms are not known, this example stimulated the development of a synthetic gene drive construct in Drosophila with the same logic . The construct combined a microRNA-based repressor of myd88 (an important protein normally supplied by the mother into the embryo) with a zygotically expressed myd88 gene that was not affected by the microRNA and supplied the missing protein.…”

Can CRISPR-Based Gene Drive Be Confined in the Wild? A Question for Molecular and Population Biology

“…One proposition is to introduce a second-generation Medea element having a distinct maternal toxin to the first and having zygotic antidotes to both the first and second-generation toxins. 12 Such a construct is expected to spread at the expense of both the first-generation Medea element and wild-type allele, with the goal of removing the effector gene from the population, albeit while leaving behind residual Medea toxin− antidote machinery (Figure 2A). It should be noted that, for both drive and remediation to be effective, the toxin and antidote must be highly efficient.…”

Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex

“…The second general type of gene drives reduces the fitness of the wild-type alleles, and thus gains an advantage by biasing selection instead of inheritance. For example, natural and synthetic Medea elements spread by causing the death of either gametes or zygotes that lack them (Akbari et al 2014;Beeman et al 1992;Chen et al 2007). Another example is gene drives based on simple, one-locus underdominance, which can cause reduced viability in heterozygotes.…”