Academic journal article Genetics

Genetically Engineered Underdominance for Manipulation of Pest Populations: A Deterministic Model

Academic journal article Genetics

Genetically Engineered Underdominance for Manipulation of Pest Populations: A Deterministic Model

Article excerpt

ABSTRACT

We theoretically investigate the potential for introgressing a desired engineered gene into a pest population by linking the desired gene to DNA constructs that exhibit underdominance properties. Our deterministic model includes two independently segregating engineered constructs that both carry a lethal gene, but suppress each other. Only genotypes containing both or neither construct are viable. Both constructs also carry the desired gene with an independent regulatory mechanism. We examine the minimal number of individuals of an engineered strain that must be released into a natural population to successfully introgress the desired gene. We compare results for strains carrying single and multiple insertions of the constructs. When there are no fitness costs associated with the inserted constructs (when the lethal sequences are not expressed), the number of individuals that must be released decreases as the number of insertions in the genome of the released strain increases. As fitness costs increase, the number of individuals that must be released increases at a greater rate for release strains with more insertions. Under specific conditions this results in the strain with only a single insertion of each construct being the most efficient for introgressing the desired gene. We discuss practical implications of our findings.

RECENTLY, there has been considerable discussion regarding the potential for decreasing the incidence of mosquito-borne diseases such as malaria and dengue on the basis of spreading engineered genes for refractoriness (i.e., inability to transmit the pathogen) into native mosquito populations (GouLD and SCHLIEKELMAN 2004). Because strains bearing these engineered refractory genes are not expected to have higher fitness than native mosquitoes (CATTERUCCIA et al. 2003; IRVIN et al. 2004; MOREIRA et al. 2004), an engineered gene with Mendelian inheritance will not increase in frequency after being released. Thus, it will be necessary to develop genetic drive systems to spread the genes controlling refractoriness.

Substantial advances have been made in engineering refractory mosquito strains (e.g., ITO et al. 2002), but only limited efforts have focused on drive mechanisms and the population genetic factors that could affect their success (RiBEiRO and KIDWELL 1994; KISZEWSKI and SPIELMAN 1998; DAVIS et al. 2001; BURT 2003; GOULD and SCHLIEKELMAN 2004).

Underdominance is one mechanism that has been proposed for driving desirable genes into populations (CuRTis 1968a,b; DAVIS et al. 2001). Underdominance is classically defined as the genetic condition where the fitness of hétérozygote individuals is lower than the fitness of both of the parental homozygotes (HARTL and CLARK 1989). There are two stable and one unstable equilibria in such a system with two alleles. At the alternate stable equilibria, one of the alleles is typically fixed and the other is lost from the population. The relationship between the initial allelic frequencies and the unstable equilibrium determines which allele becomes fixed. Underdominance is typically considered to involve a single locus, and fitness is considered as survival and reproduction in a single generation. However, if first-generation hétérozygotes are as fit as their homozygote parents, but their offspring are less fit than the offspring of homozygotes in a specific population, the same three equilibria can exist. For example, when individuals that are homozygous for alternate forms of a chromosomal translocation are mated, the hétérozygotes can be quite fit because their genomes contain one copy of all genes from both parents (ROBINSON 1976). When these hétérozygotes mate with each other a fraction of their offspring lack important chromosomal segments and are notviable. Therefore if we expand our view of fitness to multiple generations, this can be considered as a case of underdominance.

A novel form of genetically engineered underdominance has been suggested by DAVIS et al. …

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