Biology subjects

Vella, M. R.

Publications and source records attributed to Vella, M. R..

4 recordsLinked to original sources

bioRxiv2020

Mathematical modeling of genetic pest management through female lethality with independently segregating alleles

Many novel genetic approaches are under development to combat insect pests. One genetic strategy aims to suppress or locally eliminate a species through large, repeated releases of genetically engineered strains that render female offspring unviable under field conditions. Strains with this female-killing (FK) characteristic have been developed either with all of the molecular components in a single construct or with the components in two constructs inserted at independently assorting loci. Strains with two constructs are typically considered to be only of value as research tools and for producing solely male offspring in rearing factories which are subsequently sterilized by radiation before release. A concern with the two-construct strains is that once released, the two constructs would become separated and therefore non-functional. The only FK strains that have been released in the field without sterilization are single-construct strains. Here, we use a population genetics model with density dependence to evaluate the relative effectiveness of female killing approaches based on single- and two-construct arrangements. We find that, in general, the single-construct arrangement results in slightly faster population suppression, but the two-construct arrangement can eventually cause stronger suppression and cause local elimination with a smaller release size. Based on our results, there is no a priori reason that males carrying two independently segregating constructs need to be sterilized prior to release. In some cases, a fertile release would be more efficient for population suppression.Competing Interest StatementThe authors have declared no competing interest.View Full Text

evolutionary biology↗

bioRxiv2019

Development and testing of a novel Killer-Rescue self-limiting gene drive system in Drosophila melanogaster

We report the development and laboratory testing of a novel Killer-Rescue (K-R) self-limiting gene drive system in Drosophila melanogaster. This K-R system utilizes the well-characterized Gal4/UAS binary expression system and the Gal4 inhibitor, Gal80. Three killer (K) lines were tested; these used either an autoregulated UAS-Gal4 or UAS-Gal4 plus UAS-hid transgene. One universal rescue (R) line was used, UAS-Gal80, to inhibit Gal4 expression. The K lines are lethal and cause death in the absence of R. We show that Gal4 RNA levels are high in the absence of R. Death is possibly due to transcriptional squelching from high levels of Gal4. When R is present, Gal4 activation of Gal80 would lead to inhibition of Gal4 and prevent overexpression. With a single release ratio of 2:1 engineered K-R to wildtype, we find that K drives R through the population while the percent of wild type individuals decreases each generation. The choice of core promoter for a UAS-Gal4 construct strongly influences the K-R system. With the strong hsp70 core promoter, K was very effective but was quickly lost from the population. With the weaker DSCP core promoter, K persisted for longer allowing the frequency of individuals with at least one copy of R to increase to over 98%. This simple gene drive system could be readily adapted to other species such as mosquito disease vectors for driving anti-viral or anti-parasite genes.\n\nSignificanceHere we report the development and testing of a novel self-limiting gene drive system, Killer-Rescue, in Drosophila melanogaster. This system is composed of an auto-regulated Gal4 Killer (K) and a Gal4-activated Gal80 Rescue (R). Overexpression of Gal4 is lethal but in the presence of R, activation of Gal80 leads to much lower levels of Gal4 and rescue of lethality. We demonstrate that with a single 2:1 engineered to wildtype release, more than 98% of the population carry R after eight generations. We discuss how this Killer-Rescue system may be used for population replacement in a human health pest, Aedes aegypti, or for population suppression in an agricultural pest, Drosophila suzukii.

genetics↗

bioRxiv2019

Locally Fixed Alleles: A method to localize gene drive to island populations

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the \"Locally Fixed Alleles\" approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to multiple genomic alleles becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.

evolutionary biology↗

bioRxiv2017

Invasion and migration of self-limiting gene drives: a comparative analysis

Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self-limiting. Here we use a population genetics model to compare the expected characteristics of three spatially self-limiting gene drive systems: one-locus underdominance, two-locus underdominance, and daisy-chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy-chain system is the most efficient, requiring the smallest release, followed by the two-locus underdominance system, and then the one-locus underdominance system. However, when the target population exchanges migrants with a non-target population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy-chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two-locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one-locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two-locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy-chain system can, for a small set of parameter values, achieve a temporally-limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications. Note: This manuscript has been accepted for publication in the journal Evolutionary Applications and is pending publication. We suggest that any reference to or quotation of this article should be made with this recognition.

bioengineering↗