Driving Transgenes with Disassortative Mating

Anopheles stephensi.jpeg

Anopheles stephensi female, Image Credit. Jim Gathany – This media comes from the Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), with identification number #5814.

Pike et al. (2017) in a recent publication in Science describe a novel approach to rapidly increasing transgene frequencies in mosquito populations (‘gene drive’) for the purposes of reducing or eliminating Plasmodium transmission.

There is increasing attention within the insect research community to the creation of selfish genetic elements such as synthetic homing endonucleases, for example, for the purposes of rapidly introgressing transgenes into natural populations – so-called gene drives.

Pike et al. discovered that lines of Anopheles stephensi that expressed anti-Plasmodium transgenes in the midgut also showed strong disassortative mating (negative assortative mating) .  Transgenic males showed a strong mating preference for wildtype females while transgenic females showed a strong mating preference for wildtype males.

The ‘anti-Plasmodium’ transgenes in this case included Rel2 and a splice variant of Dscam under the regulatory control of the promoter/enhancer from carboxypeptidase which is activated following a blood meal.

Starting with small mixed populations consisting of equally frequent transgenic and wildtype mosquitoes in the laboratory, the authors report that in the first generation the transgene frequency rose to 90% and remained there for 10 generations.

Pike et al. performed various fitness assessments and found no significant differences between transgenic and wildtype insects that would account for the significant skewing of transgene frequencies.

Instead what they discovered was that transgenic mosquitoes had altered gut microbiomes relative to wildtype mosquitoes.  Not only was the overall abundance of gut microbes reduced in the transgenic insects but the species composition was also altered.  There is evidence from research on other insect species that the composition of gut microbiomes can impact mate selection.

Disassortative mating can result in “gene drive”

The authors tested this hypothesis by directly manipulating the gut microbiome using antibiotics and by supplementing the gut microbiome with cultivated bacteria.  The resulting data were consistent with the hypothesis that the disassortative mating observed among transgenic and wildtype mosquitoes was driven in some way by the altered microbiome of the transgenic insects resulting from the anit-bacterial effects of the transgenes.

These are very interesting results not only for providing additional support for the hypothesis that insect microbiomes impact patterns of reproduction but also because these new patterns of reproduction can results in rapid changes in transgene frequencies – at least in the laboratory.  Naturally, whether these microbiome effects on mating patterns are seen under field conditions is an interesting open question that the authors will pursue.

Andrew Pike, Yuemei Dong, Nahid Borhani Dizaji, Anthony Gacita, Emmanuel F. Mongodin, George Dimopoulos (2017) Changes in the microbiota cause genetically modified Anopheles to spread in a population,
Science 357:1396-1399

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