standard Towards a Medea Drive System in Anopheles Mosquitoes

Germ-line specific promoters are useful to insect biologists and Biedler and colleagues (2015) in a just-published paper in G3-Genes|Genomes|Genetics report their efforts to identify, isolate and test maternal germline-specific genes and promoters in the Asian malaria vector, Anopheles stephensi.

“We are interested in maternal germline‐specific genes in the An. stephensi for both fundamental and translational research purpose”    Biedler et al. (2015)

Zhijian "Jake" Tu, Ph.D., Professor, Department of Biochemistry, Virginia Tech University.

Biedler et al (2015) senior author and IGTRCN Participant Zhijian “Jake” Tu, Ph.D., Professor, Department of Biochemistry, Virginia Tech University.

A powerful synthetic gene drive system developed in Drosophila melanogaster called Medea or maternal-effect dominant embryonic arrest was described a few years ago that relied on the clever use of maternal germline specific and early zygotic promoters.

The Medea system in Drosophila serves as a prototype ‘toxin/antidote’-based genetic drive system fostering interest in the creation of similar systems in insects of agricultural and public health significance. Uses for such systems include the introgression of genes into mosquito populations that alter their vectoral capacity. Alternatively, these systems could be used to severely alter sex ratios – for example, skewing sex ratios toward males and resulting, ultimately, in collapse of the population.

The toxin-antidote - based drive system known as Medea.  Embryos without Medea will die because of maternally deposited 'toxins'.

The toxin-antidote – based drive system known as Medea. Embryos without Medea will die because of maternally deposited ‘toxins’.  Maternal germline-specific promoters are needed to express an appropriate ‘toxin’. Image from: Chen CH,Huang H,Ward CM,Su JT,Schaeffer LV,Guo M,Hay BA. (2007) A Synthetic Maternal-Effect Selfish Genetic Element Drives Population Replacement in Drosophila. Science. 2007 Apr 27;316(5824):597-600.

 

To recreate the Medea system in other insects maternal germline specific promoters are needed.

Biedler et al. identified and characterized 79 previtellogenic early ovary-specific genes in An. stephensi using genome-wide RNAseq analysis over a range of developmental stages and tissues.

RT-PCR was used to validate the expression patterns of some of the candidate genes with RNAseq data of interest.

Some of the genes identified such as nanos, vasa, vgr (vitellogenin receptor) and oskar have been described in other species and are known to have germline specific expression.

Medea is notorious for kilingl her two children fathered by Jason he forsakes her

Medea is notorious for kiling her two children fathered by Jason after he forsakes her.

Two, nanos and vgr,  were further tested in transgenic An. stephensi, confirming their expected specificity.  The promoters were also used to express artificial microRNAs against suspected mosquito maternal‐effect genes, discontinuous actin hexagon and myd88 and achieved 73% and 42% knockdown of myd88 and discontinuous actin hexagon mRNA in the ovaries 48 hours after blood-feeding.

RNA localization of the Drosophila melanogaster vitellogenin receptor gene yolkless.   Similar patterns are expected in Anopheles stephensi. Image:

RNA localization of the Drosophila melanogaster vitellogenin receptor gene yolkless.
Similar patterns are expected in Anopheles stephensi.
Image from: Schonbaum et al (2000) Regulation of the Vitellogenin Receptor during Drosophila melanogaster Oogenesis Mol. Biol. Cell 11:2 511-521; doi:10.1091/mbc.11.2.511

 

 

 

 

 

The paper of Biedler et al. represent progress toward the creation of an Anopheles mosquito gene drive system and is worth reading while the availability of mosquito maternal germline specific promoters could be useful .

 

 Maternal Germline-Specific Genes in the Asian Malaria Mosquito Anopheles stephensi: Characterization and Application for Disease Control (2014) James K. Biedler, Yumin Qi, David Pledger, Anthony James, and Zhijian Tu
G3 g3.114.015578; Early Online December 5, 2014, doi:10.1534/g3.114.015578

Related Technology Posts:

Two Bombyx Testis-Specific Promoters

Medusa: Harnessing a Sex-Linked Transgenic Drive System to Control Insect Populations

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