Mosquito transgenesis: what is the fitness cost?

Marrelli, Mauro Toledo; Moreira, Cristina K.; Kelly, Dave; Alphey, Luke; Jacobs-­Lorena, Marcelo

doi:10.1016/j.pt.2006.03.004

Cited by 140 publications

(148 citation statements)

References 48 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…Fitness costs observed in mosquitoes homozygous for the transgene could be due to hitchhiking of recessive deleterious genes residing near the point of transgene insertion (8). This would imply that such recessive deleterious genes occur fairly commonly in the mosquito genome, because a similar homozygous cost was observed with two independently derived transgenic lines.…”

Section: Resultsmentioning

confidence: 99%

“…1). Moreover, at least in Drosophila where this possibility was examined in detail, loss of fitness due to insertional mutagenesis is a rare event (8).…”

Section: Resultsmentioning

confidence: 99%

“…Catteruccia et al (6) found that Anopheles stephensi homozygous transgenic lines have lower fitness compared with WT, and Irvin et al (7) reached similar conclusions with transgenic lines of Aedes aegypti. However, these studies could not distinguish fitness effects due to the transgene itself versus insertion-site effects and/or inbreeding depression (8). In a separate study, Moreira et al (2) demonstrated that hemizygous transgenic mosquitoes expressing the SM1 dodecapeptide under the control of the blood-inducible carboxypeptidase promoter were as fit as WT controls when fed on blood of noninfected mice.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding onPlasmodium-infected blood

Marrelli

Rasgon

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

107

View full text Add to dashboard Cite

The introduction of genes that impair Plasmodium development into mosquito populations is a strategy being considered for malaria control. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this approach. We have previously shown that anopheline mosquitoes expressing the SM1 peptide in the midgut lumen are impaired for transmission of Plasmodium berghei. Moreover, the transgenic mosquitoes had no noticeable fitness load compared with nontransgenic mosquitoes when fed on noninfected mice. Here we show that when fed on mice infected with P. berghei, these transgenic mosquitoes are more fit (higher fecundity and lower mortality) than sibling nontransgenic mosquitoes. In cage experiments, transgenic mosquitoes gradually replaced nontransgenics when mosquitoes were maintained on mice infected with gametocyte-producing parasites (strain ANKA 2.34) but not when maintained on mice infected with gametocyte-deficient parasites (strain ANKA 2.33). These findings suggest that when feeding on Plasmodium-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over nontransgenic mosquitoes. This fitness advantage has important implications for devising malaria control strategies by means of genetic modification of mosquitoes. malaria control ͉ genetic modification ͉ gene drive T he use of genetically modified mosquitoes refractory to pathogen transmission is a potential strategy for controlling vector-borne diseases (1-4). In the past few years, important technical advances, including germ-line transformation of mosquitoes, the characterization of tissue-specific promoters, and the identification of molecules that interfere with parasite development (effector molecules), have led to the generation of transgenic mosquitoes that are impaired in their capacity to transmit the malaria parasite (1, 5). However, although the feasibility of genetically modifying mosquito vector competence has been demonstrated in the laboratory, we do not yet know how transgenes can be introgressed into mosquito populations in the field. Several possible approaches have been proposed (transposable elements, Wolbachia, and meiotic drive), but success of any mechanism will depend in part on the fitness load that is imposed by the presence of the transgene.Previous studies suggested that transgenic mosquitoes are less fit than wild type (WT) (6, 7). Catteruccia et al. (6) found that Anopheles stephensi homozygous transgenic lines have lower fitness compared with WT, and Irvin et al. (7) reached similar conclusions with transgenic lines of Aedes aegypti. However, these studies could not distinguish fitness effects due to the transgene itself versus insertion-site effects and/or inbreeding depression (8). In a separate study, Moreira et al. (2) demonstrated that hemizygous transgenic mosquitoes expressing the SM1 dodecapeptide under the control of the blood-inducible carboxypeptidase promoter were as fit as WT controls when fed on blood of noninfected mice.Plasmodium and other path...

show abstract

Section: Resultsmentioning

confidence: 99%

“…1). Moreover, at least in Drosophila where this possibility was examined in detail, loss of fitness due to insertional mutagenesis is a rare event (8).…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding onPlasmodium-infected blood

Marrelli

Rasgon

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

107

View full text Add to dashboard Cite

show abstract

“…In the simplest version, this works in a similar manner to radiation‐based SIT. Compared with sterilizing doses of radiation, the targeted nature of genetic engineering generally mitigates fitness reductions in transgenic insects; although some detriment in performance might occur, there will be little or no effect in the most promising candidate genetic lines (Marrelli et al ., 2006; Harvey‐Samuel et al ., 2014). This enables SIT‐like applications in further species for which a sterilizing dose of radiation can cause too much collateral damage to somatic cells and/or tissues.…”

Section: Sterile Insect Methodsmentioning

confidence: 99%

Genetics‐based methods for agricultural insect pest management

Alphey

Bonsall

2017

Agri and Forest Entomology

View full text Add to dashboard Cite

The sterile insect technique is an area‐wide pest control method that reduces agricultural pest populations by releasing mass‐reared sterile insects, which then compete for mates with wild insects. Contemporary genetics‐based technologies use insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation.Engineered strains of agricultural pest species, including moths such as the diamondback moth Plutella xylostella and fruit flies such as the Mediterranean fruit fly Ceratitis capitata, have been developed with lethality that only operates on females.Transgenic crops expressing insecticidal toxins are widely used; the economic benefits of these crops would be lost if toxin resistance spread through the pest population. The primary resistance management method is a high‐dose/refuge strategy, requiring toxin‐free crops as refuges near the insecticidal crops, as well as toxin doses sufficiently high to kill wild‐type insects and insects heterozygous for a resistance allele.Mass‐release of toxin‐sensitive engineered males (carrying female‐lethal genes), as well as suppressing populations, could substantially delay or reverse the spread of resistance. These transgenic insect technologies could form an effective resistance management strategy.We outline some policy considerations for taking genetic insect control systems through to field implementation.

show abstract

“…This often leads to position effects, which impact on the transgene functionality (6), and/or disrupts gene structure due to insertional mutagenesis, which can cause recessive lethality (12,13). These phenomena often negatively impact the overall fitness and reliability of the transgenic strain (14). However, once a fit and functional transgenic strain has been generated and characterized, it would be desirable to take advantage of such an innocuous genomic integration site to manipulate or replace the existing transgene and to introduce additional transgenes to the same genomic position.…”

mentioning

confidence: 99%

Site-specific recombination for the modification of transgenic strains of the Mediterranean fruit fly Ceratitis capitata

Schetelig

Scolari

Handler

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Insect transgenesis is mainly based on the random genomic integration of DNA fragments embedded into non-autonomous transposable elements. Once a random insertion into a specific location of the genome has been identified as particularly useful with respect to transgene expression, the ability to make the insertion homozygous, and lack of fitness costs, it may be advantageous to use that location for further modification. Here we describe an efficient method for the modification of previously inserted transgenes by the use of the site-specific integration system from phage phiC31 in a tephritid pest species, the Mediterranean fruit fly Ceratitis capitata. First, suitable transgenic strains with randomly integrated attP landing sites within transposon-based vectors were identified by molecular and functional characterization. Second, donor plasmids containing an attB site, with additional markers, and transposon ends were integrated into attP sites by phiC31 integrase-mediated recombination. Third, transposase-encoding 'jumpstarter' strains were created and mated to transgenic strains resulting in the postintegrational excision of transposon ends, which left stably integrated transgene insertions that could not be remobilized. This three-step integration and stabilization system will allow the combination of several transgeneencoded advantageous traits at evaluated genomic positions to generate optimized strains for pest control that minimize environmental concerns.insect pest management ͉ phiC31 integrase ͉ transgene stability

show abstract

Mosquito transgenesis: what is the fitness cost?

Cited by 140 publications

References 48 publications

Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding onPlasmodium-infected blood

Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding onPlasmodium-infected blood

Genetics‐based methods for agricultural insect pest management

Site-specific recombination for the modification of transgenic strains of the Mediterranean fruit fly Ceratitis capitata

Contact Info

Product

Resources

About