scholarly journals Propagation of seminal toxins through binary expression gene drives can suppress polyandrous populations

2021 ◽  
Author(s):  
Juan Hurtado ◽  
Santiago Revale ◽  
Luciano M Matzkin
Keyword(s):  
Expression System ◽  
Target Population ◽  
The Other ◽  
Gene Drive ◽  
High Frequencies ◽  
Dominant Lethal ◽  
System Components ◽  
Fertility Gene ◽  
Highly Effective ◽  
Gene Drives

Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this restriction may be relaxed by using a double gene drive design to spread a split binary expression system. One drive carries a dominant lethal/toxic effector alone and the other a transactivator factor, without which the effector will not act. Only after the drives reach sufficiently high frequencies would individuals have the chance to inherit both system components and the effector be expressed. We explore through mathematical modeling the potential of this design to spread dominant lethal/toxic alleles and suppress populations. We show that this system could be implemented to spread engineered seminal proteins designed to kill females, making it highly effective against polyandrous populations.

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

2017 ◽  
Author(s):  
Sumit Dhole ◽  
Michael R. Vella ◽  
Alun L. Loyd ◽  
Fred Gould
Keyword(s):  
Target Population ◽  
Gene Drive ◽  
Fitness Costs ◽  
Invasion And Migration ◽  
Migration Rates ◽  
Chain System ◽  
Drive Systems ◽  
And Migration ◽  
The One ◽  
Gene Drives

AbstractRecent 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.

scholarly journals Spatial structure undermines parasite suppression by gene drive cargo

2019 ◽  
Author(s):  
James J Bull ◽  
Christopher H Remien ◽  
Richard Gomulkiewicz ◽  
Stephen M Krone
Keyword(s):  
Spatial Structure ◽  
The Other ◽  
Gene Drive ◽  
High Coverage ◽  
Disease Eradication ◽  
Vector Population ◽  
Evolution Of Resistance ◽  
Disease Agent ◽  
Gene Drives ◽  
Simple Models

ABSTRACTGene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.

scholarly journals Tethered homing gene drives: a new design for spatially restricted population replacement and suppression

2018 ◽  
Author(s):  
Sumit Dhole ◽  
Alun L. Lloyd ◽  
Fred Gould
Keyword(s):  
Mathematical Model ◽  
Genetic Load ◽  
Target Population ◽  
Gene Drive ◽  
Population Replacement ◽  
Additional Release ◽  
New Gene ◽  
Gene Drives ◽  
Population Suppression ◽  
Proof Of Principle

ABSTRACTOptimism regarding potential epidemiological and conservation applications of modern gene drives is tempered by concern about the potential unintended spread of engineered organisms beyond the target population. In response, several novel gene drive approaches have been proposed that can, under certain conditions, locally alter characteristics of a population. One challenge for these gene drives is the difficulty of achieving high levels of localized population suppression without very large releases in face of gene flow. We present a new gene drive system, Tethered Homing (TH), with improved capacity for localized population alteration, especially for population suppression. The TH drive is based on driving a payload gene using a homing construct that is anchored to a spatially restricted gene drive. We use a proof of principle mathematical model to show the dynamics of a TH drive that uses engineered underdominance as an anchor. This system is composed of a split homing drive and a two-locus engineered underdominance drive linked to one part of the split drive (the Cas endonuclease). In addition to improved localization, the TH system offers the ability to gradually adjust the genetic load in a population after the initial alteration, with minimal additional release effort.

scholarly journals Designing gene drives to limit spillover to non-target populations

2019 ◽  
Author(s):  
Gili Greenbaum ◽  
Marcus W. Feldman ◽  
Noah A. Rosenberg ◽  
Jaehee Kim
Keyword(s):  
Target Population ◽  
Unintended Effects ◽  
Gene Drive ◽  
Migration Rates ◽  
Target Populations ◽  
Disease Vector ◽  
Narrow Region ◽  
Natural Settings ◽  
Gene Drives ◽  
High Migration

AbstractThe prospect of utilizing CRISPR-based gene-drive technology for controlling populations, such as invasive and disease-vector species, has generated much excitement. However, the potential for spillovers of gene drive alleles from the target population to non-target populations — events that may be ecologically catastrophic — has raised concerns. Here, using two-population mathematical models, we investigate the possibility of limiting spillovers and impact on non-target populations by designing differential-targeting gene drives, in which the expected equilibrium gene drive allele frequencies are high in the target population but low in the non-target population. We find that achieving differential targeting is possible with certain configurations of gene drive parameters. Most of these configurations ensure differential targeting only under relatively low migration rates between target and non-target populations. Under high migration, differential targeting is possible only in a narrow region of the parameter space. When migration is increased, differential-targeting states can sharply transition to states of global fixation or global loss of the gene drive. Because fixation of the gene drive in the non-target population could severely disrupt ecosystems, we outline possible ways to avoid this outcome. Our results emphasize that, although gene drive technology is promising, understanding the potential consequences for populations other than the targets requires detailed analysis of gene-drive spillovers, and that ways to limit the unintended effects of gene drives to non-target populations should be explored prior to the application of gene drives in natural settings.

scholarly journals Modeling the mutation and reversal of engineered underdominance gene drives

2018 ◽  
Author(s):  
Matthew P. Edgington ◽  
Luke S. Alphey
Keyword(s):  
Genetic Material ◽  
Theoretical Work ◽  
The Other ◽  
Lethal Gene ◽  
Gene Drive ◽  
Loss Of Function ◽  
Wild Type ◽  
Type Population ◽  
Drive Systems ◽  
Gene Drives

AbstractA range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, is based on the introduction of two independently segregating transgenic constructs each carrying a lethal gene, a suppressor for the lethal at the other locus and a desirable genetic “cargo”. Under this system individuals carrying at least one copy of each construct (or no copies of either) are viable whilst those that possess just one of the transgenic constructs are non-viable. Previous theoretical work has explored various properties of these systems, concluding that they should persist indefinitely in absence of resistance or mutation. Here we study a population genetics model of UD gene drive that relaxes past assumptions by allowing for loss-of-function mutations in each introduced gene. We demonstrate that mutations are likely to cause UD systems to break down, eventually resulting in the elimination of introduced transgenes. We then go on to investigate the potential of releasing “free suppressor” carrying individuals as a new method for reversing UD gene drives and compare this to the release of wild-types; the only previously proposed reversal strategy for UD. This reveals that while free suppressor carrying individuals may represent an inexpensive reversal strategy due to extremely small release requirements, they are not able to return a fully wild-type population as rapidly as the release of wild-types.

scholarly journals Gene Drives Across Engineered Fitness Valleys: Modeling a Design to Prevent Drive Spillover

2020 ◽  
Author(s):  
Frederik J.H. de Haas ◽  
Sarah P. Otto
Keyword(s):  
Local Population ◽  
Target Population ◽  
Drive System ◽  
High Threshold ◽  
Gene Drive ◽  
Time Model ◽  
Population Replacement ◽  
Low Threshold ◽  
Drive Systems ◽  
Gene Drives

1AbstractEngineered gene drive techniques for population replacement and/or suppression have potential for tackling complex challenges, including reducing the spread of diseases and invasive species. Unfortunately, the self-propelled behavior of drives can lead to the spread of transgenic elements beyond the target population, which is concerning. Gene drive systems with a low threshold frequency for invasion, such as homing-based gene drive systems, require initially few transgenic individuals to spread and are therefore easy to implement. However their ease of spread presents a double-edged sword; their low threshold makes these drives much more susceptible to spread outside of the target population (spillover). We model a proposed drive system that transitions in time from a low threshold drive system (homing-based gene drive) to a high threshold drive system (underdominance) using daisy chain technology. This combination leads to a spatially restricted drive strategy, while maintaining an attainable release threshold. We develop and analyze a discrete-time model as proof of concept and find that this technique effectively generates stable local population suppression, while preventing the spread of transgenic elements beyond the target population under biologically realistic parameters.

scholarly journals Designing gene drives to limit spillover to non-target populations

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009278
Author(s):  
Gili Greenbaum ◽  
Marcus W. Feldman ◽  
Noah A. Rosenberg ◽  
Jaehee Kim
Keyword(s):  
Target Population ◽  
Field Trials ◽  
Gene Drive ◽  
Migration Rates ◽  
Target Populations ◽  
Narrow Region ◽  
Theoretical Predictions ◽  
Potential Applications ◽  
And Control ◽  
Gene Drives

The prospect of utilizing CRISPR-based gene-drive technology for controlling populations has generated much excitement. However, the potential for spillovers of gene-drive alleles from the target population to non-target populations has raised concerns. Here, using mathematical models, we investigate the possibility of limiting spillovers to non-target populations by designing differential-targeting gene drives, in which the expected equilibrium gene-drive allele frequencies are high in the target population but low in the non-target population. We find that achieving differential targeting is possible with certain configurations of gene-drive parameters, but, in most cases, only under relatively low migration rates between populations. Under high migration, differential targeting is possible only in a narrow region of the parameter space. Because fixation of the gene drive in the non-target population could severely disrupt ecosystems, we outline possible ways to avoid this outcome. We apply our model to two potential applications of gene drives—field trials for malaria-vector gene drives and control of invasive species on islands. We discuss theoretical predictions of key requirements for differential targeting and their practical implications.

scholarly journals Spatial structure undermines parasite suppression by gene drive cargo

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7921 ◽  
Author(s):  
James J. Bull ◽  
Christopher H. Remien ◽  
Richard Gomulkiewicz ◽  
Stephen M. Krone
Keyword(s):  
Spatial Structure ◽  
The Other ◽  
Gene Drive ◽  
High Coverage ◽  
Disease Eradication ◽  
Vector Population ◽  
Evolution Of Resistance ◽  
Disease Agent ◽  
Gene Drives ◽  
Simple Models

Gene drives may be used in two ways to curtail vectored diseases. Both involve engineering the drive to spread in the vector population. One approach uses the drive to directly depress vector numbers, possibly to extinction. The other approach leaves intact the vector population but suppresses the disease agent during its interaction with the vector. This second application may use a drive engineered to carry a genetic cargo that blocks the disease agent. An advantage of the second application is that it is far less likely to select vector resistance to block the drive, but the disease agent may instead evolve resistance to the inhibitory cargo. However, some gene drives are expected to spread so fast and attain such high coverage in the vector population that, if the disease agent can evolve resistance only gradually, disease eradication may be feasible. Here we use simple models to show that spatial structure in the vector population can greatly facilitate persistence and evolution of resistance by the disease agent. We suggest simple approaches to avoid some types of spatial structure, but others may be intrinsic to the populations being challenged and difficult to overcome.

scholarly journals Modeling homing suppression gene drive in haplodiploid organisms

2021 ◽  
Author(s):  
Yiran Liu ◽  
Jackson Champer
Keyword(s):  
Great Promise ◽  
Resistance Allele ◽  
Gene Drive ◽  
Wild Type ◽  
Target Species ◽  
Strong Suppression ◽  
Continuous Space ◽  
Cleavage Activity ◽  
Fertility Gene ◽  
Gene Drives

Gene drives have shown great promise for suppression of pest populations. These engineered alleles can function by a variety of mechanisms, but the most common is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of heterozygotes. Some potential target species are haplodiploid, in which males develop from unfertilized eggs and thus have only one copy of each chromosome. This prevents drive conversion, a substantial disadvantage compared to diploids where drive conversion can take place in both sexes. Here, we study the characteristics of homing suppression gene drives in haplodiploids and find that a drive targeting a female fertility gene could still be successful. However, such drives are less powerful than in diploids. They are substantially more vulnerable to high resistance allele formation in the embryo due to maternally deposited Cas9 and gRNA and also to somatic cleavage activity. Examining models of continuous space where organisms move over a landscape, we find that haplodiploid suppression drives surprisingly perform nearly as well as in diploids, possibly due to their ability to spread further before inducing strong suppression. Together, these results indicate that gene drive can potentially be used to effectively suppress haplodiploid populations.

Pengaruh Kotbah, Musik Gereja Dan Fasilitas Gereja Terhadap Tingkat Kehadiran Jemaat

2016 ◽  
Vol 1 (1) ◽  
pp. 1-15
Author(s):  
Frederich Oscar Lontoh
Keyword(s):  
Regression Analysis ◽  
Multiple Regression Analysis ◽  
Church Music ◽  
Pearson Correlation ◽  
Descriptive Analysis ◽  
Target Population ◽  
The Other ◽  
Pearson Correlation Coefficient ◽  
Christian Church ◽  
The City

This research is titled " The influence of sermon, church music and church facilities on the level of attendance”. The purpose of research is to identify and analyze whether sermon, church music and church facilities have influence on the the level of attendance. The target population in this study is a Christian church members who live in the city of Surabaya.. Sample required is equal to 47 respondents. Through sampling stratified Random techniques.These influence was measured using Pearson correlation coefficient and multiple regression analysis, t-test and analysis of variance. Descriptive  analysis  were taken to analyze the level of attendance according to demographic groups.The hypothesis in this study are the sermon, church music and church facilities have positive and significant on the level of attendance. The results showed that collectively, there are positive and significant correlation among the sermon, church music and church facilities on the level of attendance  96,2%. It means that 96,2 % of level of attendance influenced by sermon, church music and church facilities and the other 28,9% by others. All of the variable partially have significant correlation to level of attendance.

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