scholarly journals Engineered reciprocal chromosome translocations drive high threshold, reversible population replacement in Drosophila

2016 ◽  
Author(s):  
Anna B. Buchman ◽  
Tobin Ivy ◽  
John M. Marshall ◽  
Omar S. Akbari ◽  
Bruce A. Hay

AbstractReplacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions provides self-perpetuating methods of disease prevention and population suppression, respectively. Gene drive mechanisms that require the gene drive element and linked cargo exceed a high threshold frequency to spread are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold required for drive. It has long been recognized that reciprocal chromosome translocations could, in principal, be used to bring about high threshold gene drive through a form of underdominance. However, translocations able to drive population replacement have not been reported, leaving it unclear if translocation-bearing strains fit enough to mediate gene drive can easily be generated. Here we use modeling to identify a range of conditions under which translocations should spread, and the equilibrium frequencies achieved, given specific introduction frequencies, fitness costs and migration rates. We also report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. By several measures translocation-bearing strains are fit, and drive high threshold, reversible population replacement in laboratory populations. These observations, together with the generality of the tools used to generate translocations, suggest that engineered translocations may be useful for controlled population replacement in many species.

2018 ◽  
Vol 7 (5) ◽  
pp. 1359-1370 ◽  
Author(s):  
Anna B. Buchman ◽  
Tobin Ivy ◽  
John M. Marshall ◽  
Omar S. Akbari ◽  
Bruce A. Hay

2017 ◽  
Author(s):  
Sumit Dhole ◽  
Michael R. Vella ◽  
Alun L. Loyd ◽  
Fred Gould

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.


2020 ◽  
Author(s):  
Frederik J.H. de Haas ◽  
Sarah P. Otto

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.


Genetics ◽  
1993 ◽  
Vol 133 (3) ◽  
pp. 711-727
Author(s):  
B K Epperson

Abstract The geographic distribution of genetic variation is an important theoretical and experimental component of population genetics. Previous characterizations of genetic structure of populations have used measures of spatial variance and spatial correlations. Yet a full understanding of the causes and consequences of spatial structure requires complete characterization of the underlying space-time system. This paper examines important interactions between processes and spatial structure in systems of subpopulations with migration and drift, by analyzing correlations of gene frequencies over space and time. We develop methods for studying important features of the complete set of space-time correlations of gene frequencies for the first time in population genetics. These methods also provide a new alternative for studying the purely spatial correlations and the variance, for models with general spatial dimensionalities and migration patterns. These results are obtained by employing theorems, previously unused in population genetics, for space-time autoregressive (STAR) stochastic spatial time series. We include results on systems with subpopulation interactions that have time delay lags (temporal orders) greater than one. We use the space-time correlation structure to develop novel estimators for migration rates that are based on space-time data (samples collected over space and time) rather than on purely spatial data, for real systems. We examine the space-time and spatial correlations for some specific stepping stone migration models. One focus is on the effects of anisotropic migration rates. Partial space-time correlation coefficients can be used for identifying migration patterns. Using STAR models, the spatial, space-time, and partial space-time correlations together provide a framework with an unprecedented level of detail for characterizing, predicting and contrasting space-time theoretical distributions of gene frequencies, and for identifying features such as the pattern of migration and estimating migration rates in experimental studies of genetic variation over space and time.


Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 429-446 ◽  
Author(s):  
Jinliang Wang ◽  
Michael C Whitlock

Abstract In the past, moment and likelihood methods have been developed to estimate the effective population size (Ne) on the basis of the observed changes of marker allele frequencies over time, and these have been applied to a large variety of species and populations. Such methods invariably make the critical assumption of a single isolated population receiving no immigrants over the study interval. For most populations in the real world, however, migration is not negligible and can substantially bias estimates of Ne if it is not accounted for. Here we extend previous moment and maximum-likelihood methods to allow the joint estimation of Ne and migration rate (m) using genetic samples over space and time. It is shown that, compared to genetic drift acting alone, migration results in changes in allele frequency that are greater in the short term and smaller in the long term, leading to under- and overestimation of Ne, respectively, if it is ignored. Extensive simulations are run to evaluate the newly developed moment and likelihood methods, which yield generally satisfactory estimates of both Ne and m for populations with widely different effective sizes and migration rates and patterns, given a reasonably large sample size and number of markers.


2018 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Diana Sequeira ◽  
Catarina Seabra ◽  
Paulo Palma ◽  
Ana Cardoso ◽  
João Peça ◽  
...  

Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.


2018 ◽  
Vol 10 (11) ◽  
pp. 1733 ◽  
Author(s):  
Noelia Abascal Zorrilla ◽  
Vincent Vantrepotte ◽  
Erwan Gensac ◽  
Nicolas Huybrechts ◽  
Antoine Gardel

The coast of French Guiana is characterised by the northwestward migration of large mud banks alongshore and by high concentrations of suspended particulate matter (SPM) resulting from the strong influence of the Amazon River outflow. Surface OLI SPM concentration, linked to the footprint of the subtidal part of mud banks due to resuspension and migration processes, was used to develop a method to estimate the location of this footprint. A comparison of the results from this method with those obtained by locating the limit of the wave damping, which characterises muddy coasts, revealed good performance of the method based on recurring SPM values. The migration rates of the mud banks in French Guiana were calculated according to the delimitation of their subtidal parts, and showed slightly higher values (2.31 km/year) than suggested by earlier studies. In comparison with other methods, the migration rate estimated using the method proposed within the framework of this study takes into account the variability of the shape of the subtidal part for the first time. It was also shown that the mud banks existing on the coastal area of French Guiana present two different shapes. Our results clearly demonstrate the advantage of ocean colour data to describe mud banks according to their subtidal part, delimited using the assessment of SPM temporal variability.


2012 ◽  
Vol 1 (33) ◽  
pp. 93
Author(s):  
Antony Thorpe ◽  
Jon Miles ◽  
Gerd Masselink ◽  
Paul Russell ◽  
Tim Scott ◽  
...  

A Sand Ripple Profiler (SRP) was deployed in a rip channel on a dissipative sandy beach to measure bedform height (∆), length (λ) and migration rate (Mr¬) throughout a macro-tidal cycle with an offshore significant wave height of 0.7 m and peak period of 10 s. At lower tidal elevations in the strong offshore flow of the rip current (maximum = 0.4 m/s) bedforms (∆ = 0.15 m, λ = 3 m) were found to migrate offshore (Mr = 0.21 m/hr). Outside of active rip current conditions (water depth (h) = >~2.5 m) bedforms were found to be of smaller scale (∆ = 0.09 – 0.12 m, λ = 1 – 1.2 m) migrating onshore at a rate of 0.35 m/hr at mid tide (h = 3.3 m) and 0.03 m/hr at high tide (h = 6.3 m). Onshore migration rates were found to increase with increased wave skewness and velocity variance.


Complexity ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Tousheng Huang ◽  
Huayong Zhang ◽  
Xuebing Cong ◽  
Ge Pan ◽  
Xiumin Zhang ◽  
...  

The topic of utilizing coupled map lattice to investigate complex spatiotemporal dynamics has attracted a lot of interest. For exploring the spatiotemporal complexity of a predator-prey system with migration and diffusion, a new three-chain coupled map lattice model is developed in this research. Based on Turing instability analysis, pattern formation conditions for the predator-prey system are derived. Via numerical simulation, rich Turing patterns are found with subtle self-organized structures under diffusion-driven and migration-driven mechanisms. With the variation of migration rates, the predator-prey system exhibits a gradual dynamical transition from diffusion-driven patterns to migration-driven patterns. Moreover, new results, the self-organization of non-Turing patterns, are also revealed. We find that even in the cases where the nonspatial predator-prey system reaches collapse, the migration can still drive pattern self-organization. These non-Turing patterns suggest many new possible ways for the coexistence of predator and prey in space, under the effects of migration and diffusion.


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