Academic journal article Genetics

The Population Genetics of Using Homing Endonuclease Genes in Vector and Pest Management

Academic journal article Genetics

The Population Genetics of Using Homing Endonuclease Genes in Vector and Pest Management

Article excerpt

ABSTRACT

Homing endonuclease genes (HEGs) encode proteins that in the heterozygous state cause double-strand breaks in the homologous chromosome at the precise position opposite the HEG. If the double-strand break is repaired using the homologous chromosome, the HEG becomes homozygous, and this represents a powerful genetic drive mechanism that might be used as a tool in managing vector or pest populations. HEGs may be used to decrease population fitness to drive down population densities (possibly causing local extinction) or, in disease vectors, to knock out a gene required for pathogen transmission. The relative advantages of HEGs that target viability or fecundity, that are active in one sex or both, and whose target is expressed before or after homing are explored. The conditions under which escape mutants arise are also analyzed. A different strategy is to place HEGs on the Y chromosome that cause one or more breaks on the X chromosome and so disrupt sex ratio. This strategy can cause severe sex-ratio biases with efficiencies that depend on the details of sperm competition and zygote mortality. This strategy is probably less susceptible to escape mutants, especially when multiple X shredders are used.

(ProQuest: ... denotes formulae omitted.)

THE possibility of controlling man's major pests, pathogens, and disease vectors using genetic manipulation has long been discussed (Hamilton 1967; Curtis 1968) and is of great current interest (Turelli and Hoffmann 1999; Alphey et al. 2002; James 2005; Sinkins and Gould 2006). A broad spectrum of possible strategies has been explored. Organisms can be manipulated to be conditionally sterile or lethal and released into the environment to disrupt mating or to reduce the fecundity of the wild population (Thomas et al. 2000; Atkinson et al. 2007; Phuc et al. 2007). With these inundative techniques the manipulated construct is not required to persist in the environment. A different approach is to introduce a beneficial genetic construct into a wild population with a drive mechanism that causes it to increase in frequency. The construct might impose a fitness load on the population, reducing its density or causing it to go extinct. Alternatively, it may alter the phenotype of the organism with no or minor changes to its fitness. The latter is of particular relevance to disease vectors where it may be possible to reduce or eliminate transmission. Recent advances in molecular genetics have demonstrated that knocking out certain Anopheles mosquito genes, or inserting new constructs, prevents the insect from transmitting Plasmodium, the malaria pathogen (Ito et al. 2002; Moreira et al. 2002), while RNAi techniques have been used to prevent Aedes mosquitoes from transmitting the dengue virus (Franz et al. 2006). Enthusiasm for these control strategies is tempered by the realization that any method involving genetic manipulation will require the highest scrutiny and investigation prior to implementation and that support from the public will be essential for any project to go ahead (Alphey et al. 2002; James 2005; Knols et al. 2006).

A variety of different mechanisms for driving genes through a population have been considered, most of them based on elements with non-Mendelian heritance that have been discovered in nature (Burt and Trivers 2006). Some genes cause the chromosomes on which they reside to be overrepresented in the gamete pool and thus could be used to increase the frequency of an introduced linked gene (Burt and Trivers 2006). Genetic constructs can be designed that show underdominance-heterozygote inferiority-and hence will increase in frequency once their abundance passes a certain threshold (Davis et al. 2001; Magori and Gould 2006). Elements that jump between chromosomes can be used as vectors for beneficial constructs, and transposable elements in particular have received a lot of attention (Coates et al. 1998). Heterozygote females carrying medea elements modify their eggs such that they survive only if they carry the medea gene or are fertilized by sperm that carry the element. …

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