Selfish genes may drive out diseases

Researchers have come up with a new way to establish desirable genes in insect populations, according to an online Science report this week. The authors created a synthetic selfish genetic element that propagates rapidly through Drosophila populations -- an approach they say could also help drive malaria-resistance genes into mosquito populations.The approach "looks very convincing" for establishing disease-resistance genes in insect populations, said Marcelo Jacobs-Lorena of Johns Hopkins Bloomberg School of Public Health in Baltimore, who was not involved in the study. "If it works in Drosophila, I think the chances that it would work in insects of medical importance is quite high."Researchers have identified and created mosquitoes that carry genetic elements preventing them from transmitting malaria or dengue; last week, Jacobs-Lorena and his colleagues showed that one type of malaria-resistant mosquito can outcompete normal mosquitoes when feeding on infected blood, although this advantage may not be enough to establish the resistance gene in a mosquito population. Consequently, researchers are searching for ways to ensure that such resistance genes become ubiquitous throughout an insect population, said study senior author Bruce Hay of the California Institute of Technology in Pasadena.Led by Chun-Hong Chen, also of Caltech, the researchers created a synthetic genetic element based on Medea(maternal-effect dominant embryonic arrest) elements. These selfish genetic elements are thought to select for their own survival through a toxin-antidote system, Hay said. The mother's Medea element causes toxin release into all of her oocytes, and only those progeny that inherit the Medea element themselves can produce an antidote.The researchers constructed a transposable element vector containing both a toxin and an antidote. The "toxin" consists of two microRNAs that silence expression of a crucial development gene called myd88. When myd88 is silenced in ooctyes, embryos suffer ventral patterning defects and fail to hatch. The antidote consists of a myd88 replacement. "The toxin is a loss of an essential function, and the antidote is the restoration of that function," Hay explained.The transposable element worked as expected: When female flies containing the element mated with wild-type males, about half of the progeny suffered patterning defects and died. The other half inherited the embryonic antidote and survived. To see if this element could establish itself in a population, the researchers performed cage experiments. When 25% of the flies started out with the genetic element, all flies contained at least one copy of the element after 10-12 generations. "The next step will be to add an effector gene" to the vector, such as a gene that induces resistance to malaria, according to Frederic Tripet of Keele University in Staffordshire, UK, who was not involved in the work. That way, the vector could be used to propagate this gene through an insect population, ideally mosquitoes that can carry the virus.Currently, for the mosquito, scientists still know very little about the genes and promoters in oogenesis and early embryogenesis that would have to be involved in spreading the disease-resistant genes, Hay said. But, according to Tripet, "this is just a question of time, not a major difficulty."One potential obstacle for establishing this genetic element in the wild is that mosquito populations can be reproductively isolated from one another, Tripet told The Scientist. "It is likely that the more we study those populations, the more reproductive barriers we will find that can locally prevent or slow down the spread of introduced transgenes."Genetically altered mosquitoes will have to be released in large numbers into affected areas in order for introduced genes to establish themselves, Hay said, but previous efforts to release sterile mosquitoes have shown that this is feasible. "Getting the numbers up will always be a challenge... but we know that it can be done."Melissa Lee Phillips mail@the-scientist.comLinks within this articleC.-H. Chen et al., "A Synthetic Maternal-Effect Selfish Genetic Element Drives Population Replacement in Drosophila," Science, published online March 29, 2007. http://www.sciencemag.orgA.A. James, "Gene drive systems in mosquitoes: rules of the road," Trends in Parasitology, February 2005. 'http://www.the-scientist.com/pubmed/15664528J. Weitzman, "Molecular make-up of a malaria mosquito," The Scientist, October 3, 2002. http://www.the-scientist.com/article/display/20745/Marcelo Jacobs-Lorena http://faculty.jhsph.edu/Default.cfm?faculty_id=659K.D. Vernick et al., "Molecular genetics of mosquito resistance to malaria parasites," Current Topics in Microbiology and Immunology, 2005. http://www.the-scientist.com/pubmed/16265899S. Sanides, "The malaria hut," The Scientist, August 1, 2006. http://www.the-scientist.com/article/display/24070/M.L. Phillips, "Anti-malaria genes give mosquitoes an edge," The Scientist, March 20, 2007. http://www.its.caltech.edu/~haylab/R.W. Beeman et al., "Maternal-effect selfish genes in flour beetles," Science, April 3, 1992. http://www.the-scientist.com/pubmed/1566060Frederic Tripet http://www.keele.ac.uk/research/istm/tripet.htmlG. Davidson, "The five mating types of the Anopheles gambiae complex," Rivista di Malariologia, December 1964. http://www.the-scientist.com/pubmed/14318975F. Gould, P. Schliekelman, "Population genetics of autocidal control and strain replacement," Annual Review of Entomology, 2004. http://www.the-scientist.com/pubmed/14651462

Selfish genes may drive out diseases

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