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Gene drives and the introgression of background genes into wild populations – Part I

The use of gene drives – or any genetic pest management method – involves releasing gene drive-carrying organisms, e.g. mosquitoes, to mate with wild mosquitoes in the target area. Their offspring carry the gene drive which then goes off to do whatever it was designed to do. But what about all the other (non-gene-drive) genes in the released mosquitoes? What happens to them? They also enter the population’s gene pool, though unlike the gene drive they have no special mechanism to allow them to spread. Does that matter? Contrary to some recent speculation, probably not, at least in most cases.

Genetic control of mosquitoes involves introducing some sort of modified heritable trait into a wild mosquito population. That involves rearing modified mosquitoes in the lab and releasing them to mate with the target wild mosquito population. That mating delivers the modified genetic trait into the wild population and, if that’s a gene drive and the conditions are right, that gene drive will start to do its thing in that population, for example start to increase in frequency.

That initial mating produces hybrids in the wild that carry the gene drive – but they also inherit one copy of all the other genes of the lab strain. These are not transgenic or deliberately modified in any way, but nonetheless… does it matter? I argue in this series of posts that the answer is “not much”, with a few provisos, and also that there is some potential to use this phenomenon for additional beneficial impact. This commentary was stimulated by a recent paper that made some unfounded speculation to the contrary in relation to a Oxitec’s recent field trial with a (non-gene-drive) transgenic strain of the mosquito Aedes aegypti. At time of writing, the paper had an Editor’s Note “readers are alerted that the conclusions of this paper are subject to criticisms that are being considered by editors.” So first, what about that paper?

The paper showed that sequence variants (single nucleotide polymorphisms, SNPs) present in the background (non-transgene) genome of Oxitec’s release strain, called OX513A and originally described as LA513A in the study published by Phuc et al, could be detected in field-caught mosquitoes from the release site, following multi-month releases of a ‘engineered sterile male’ strain of Aedes aegypti.

Was that expected? Well, certainly the issue had been considered. Laboratory studies had shown that while the overwhelming majority of offspring of the engineered ‘sterile’ males fail to develop to functional adults, approximately 3%-5% do survive as indicated in various papers (including this one from Phuc et al). That would be more than enough to allow some introgression of background genes, which is what this paper examines. But those surviving adults were rather weak in the lab and it was not at all clear that they would be able to reproduce in the field. That’s what this paper set out to examine and it is clear that at least a few of that small proportion of survivors could reproduce (see articles published at Nature Scientific Reports and Entomologia Experimentalis et Applicata). Which is interesting, but not of much significance in terms of using this method for control – incomplete sterility is the norm for traditional sterile-male methods using radiation-sterilised males, for example. Indeed, excellent suppression of the target population was observed – up to 90% or so, depending on the metric used, in line with other similar trials with this strain and method.

Unfortunately, the paper contained some unfounded speculation at the end regarding the potential impact of such gene flow, which led to quite a few negative stories in the press that amplified these errors.

All this puts the spotlight on the question “what is the impact of introgressing background genetic information from a release strain into a wild population”? This will be addressed in the second post of this series.

Written by Luke Alphey, who has been interested in genetic control systems for 25 years. He co-founded Oxitec Ltd in 2002 while at the University of Oxford and was Oxitec’s CSO until 2014 when he returned to public-sector research, at The Pirbright Institute. He no longer has any financial interest in Oxitec. This is the first post of two examining the implications of recent interventions carried out by Oxitec in Brazil and their potential environmental and health implications. The second post is available here.

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