scholarly journals Gene drive for population genetic control: non-functional resistance and parental effects

2019 ◽  
Vol 286 (1914) ◽  
pp. 20191586 ◽  
Author(s):  
Andrea K. Beaghton ◽  
Andrew Hammond ◽  
Tony Nolan ◽  
Andrea Crisanti ◽  
Austin Burt

Gene drive is a natural process of biased inheritance that, in principle, could be used to control pest and vector populations. As with any form of pest control, attention should be paid to the possibility of resistance evolving. For nuclease-based gene drive aimed at suppressing a population, resistance could arise by changes in the target sequence that maintain function, and various strategies have been proposed to reduce the likelihood that such alleles arise. Even if these strategies are successful, it is almost inevitable that alleles will arise at the target site that are resistant to the drive but do not restore function, and the impact of such sequences on the dynamics of control has been little studied. We use population genetic modelling of a strategy targeting a female fertility gene to demonstrate that such alleles may be expected to accumulate, and thereby reduce the reproductive load on the population, if nuclease expression per se causes substantial heterozygote fitness effects or if parental (especially paternal) deposition of nuclease either reduces offspring fitness or affects the genotype of their germline. All these phenomena have been observed in synthetic drive constructs. It will, therefore, be important to allow for non-functional resistance alleles in predicting the dynamics of constructs in cage populations and the impacts of any field release.

2018 ◽  
Author(s):  
Andrew Hammond ◽  
Xenia Karlsson ◽  
Ioanna Morianou ◽  
Kyros Kyrou ◽  
Andrea Beaghton ◽  
...  

AbstractCRISPR-Cas9 nuclease-based gene drives rely on inducing chromosomal breaks in the germline that are repaired in ways that lead to a biased inheritance of the drive. Gene drives designed to impair female fertility can suppress populations of the mosquito vector of malaria. However, strong unintended fitness costs, due to ectopic nuclease expression, and high levels of resistant mutations, limited the potential of the first generation of gene drives to spread.Here we show that changes to regulatory sequences in the drive element, designed to contain nuclease expression to the germline, confer improved fecundity over previous versions and generate drastically lower rates of target site resistance. We employed a genetic screen to show that this effect is explained by reduced rates of end-joining repair of DNA breaks at the target site caused by deposited nuclease in the embryo.Highlighting the impact of deposited Cas9, many of the mutations arising from this source of nuclease activity in the embryo are heritable, thereby having the potential to generate resistant target sites that reduce the penetrance of the gene drive.Finally, in cage invasion experiments these gene drives show improved invasion dynamics compared to first generation drives, resulting in greater than 90% suppression of the reproductive output and a delay in the emergence of target site resistance, even at a resistance-prone target sequence. We shed light on the dynamics of generation and selection of resistant alleles in a population by tracking, longitudinally, the frequency of resistant alleles in the face of an invading gene drive. Our results illustrate important considerations for future gene drive design and should expedite the development of gene drives robust to resistance.


Erdkunde ◽  
2020 ◽  
Vol 74 (3) ◽  
pp. 191-204
Author(s):  
Marcus Hübscher ◽  
Juana Schulze ◽  
Felix zur Lage ◽  
Johannes Ringel

Short-term rentals such as Airbnb have become a persistent element of today’s urbanism around the globe. The impacts are manifold and differ depending on the context. In cities with a traditionally smaller accommodation market, the impacts might be particularly strong, as Airbnb contributes to ongoing touristification processes. Despite that, small and medium-sized cities have not been in the centre of research so far. This paper focuses on Santa Cruz de Tenerife as a medium-sized Spanish city. Although embedded in the touristic region of the Canary Islands, Santa Cruz is not a tourist city per se but still relies on touristification strategies. This paper aims to expand the knowledge of Airbnb’s spatial patterns in this type of city. The use of data collected from web scraping and geographic information systems (GIS) demonstrates that Airbnb has opened up new tourism markets outside of the centrally established tourist accommodations. It also shows that the price gap between Airbnb and the housing rental market is broadest in neighbourhoods that had not experienced tourism before Airbnb entered the market. In the centre the highest prices and the smallest units are identified, but two peripheral quarters stand out. Anaga Mountains, a natural and rural space, has the highest numbers of Airbnb listings per capita. Suroeste, a suburban quarter, shows the highest growth rates on the rental market, which implies a linkage between Airbnb and suburbanization processes.


Author(s):  
Adrien Oliva ◽  
Raymond Tobler ◽  
Alan Cooper ◽  
Bastien Llamas ◽  
Yassine Souilmi

Abstract The current standard practice for assembling individual genomes involves mapping millions of short DNA sequences (also known as DNA ‘reads’) against a pre-constructed reference genome. Mapping vast amounts of short reads in a timely manner is a computationally challenging task that inevitably produces artefacts, including biases against alleles not found in the reference genome. This reference bias and other mapping artefacts are expected to be exacerbated in ancient DNA (aDNA) studies, which rely on the analysis of low quantities of damaged and very short DNA fragments (~30–80 bp). Nevertheless, the current gold-standard mapping strategies for aDNA studies have effectively remained unchanged for nearly a decade, during which time new software has emerged. In this study, we used simulated aDNA reads from three different human populations to benchmark the performance of 30 distinct mapping strategies implemented across four different read mapping software—BWA-aln, BWA-mem, NovoAlign and Bowtie2—and quantified the impact of reference bias in downstream population genetic analyses. We show that specific NovoAlign, BWA-aln and BWA-mem parameterizations achieve high mapping precision with low levels of reference bias, particularly after filtering out reads with low mapping qualities. However, unbiased NovoAlign results required the use of an IUPAC reference genome. While relevant only to aDNA projects where reference population data are available, the benefit of using an IUPAC reference demonstrates the value of incorporating population genetic information into the aDNA mapping process, echoing recent results based on graph genome representations.


2015 ◽  
Vol 11 (3) ◽  
pp. 20150012 ◽  
Author(s):  
Kenneth Wilson ◽  
Robert I. Graham

There is an increasing appreciation of the importance of transgenerational effects on offspring fitness, including in relation to immune function and disease resistance. Here, we assess the impact of parental rearing density on offspring resistance to viral challenge in an insect species expressing density-dependent prophylaxis (DDP); i.e. the adaptive increase in resistance or tolerance to pathogen infection in response to crowding. We quantified survival rates in larvae of the cotton leafworm ( Spodoptera littoralis ) from either gregarious- or solitary-reared parents following challenge with the baculovirus S. littoralis nucleopolyhedrovirus. Larvae from both the parental and offspring generations exhibited DDP, with gregarious-reared larvae having higher survival rates post-challenge than solitary-reared larvae. Within each of these categories, however, survival following infection was lower in those larvae from gregarious-reared parents than those from solitary-reared, consistent with a transgenerational cost of DDP immune upregulation. This observation demonstrates that crowding influences lepidopteran disease resistance over multiple generations, with potential implications for the dynamics of host–pathogen interactions.


Author(s):  
Luis E. Rodríguez de Francisco ◽  
Rosanna Carreras-De León ◽  
Rafael M. Navarro Cerrillo ◽  
Liz A. Paulino-Gervacio ◽  
María-Dolores Rey ◽  
...  

<i>Pinus occidentalis</i> is the dominant species of forest ecosystems in the Dominican Republic, located between 200 and 3000 meters above sea level, with extensive and overexploited natural populations. However, over the years, various restoration plans have been performed, which could affect the genetic structure of <i>P. occidentalis</i>. Despite being the species with the highest occurrence in the Dominican forests, there is no existing information on genetic structure and molecular characterization among natural populations with limited information on both phenological and productive characterization. In this study, the genetic structure, diversity, and gene flow of the five <i>P. occidentalis</i> natural populations of the Dominican Republic were determined using microsatellite markers. A total of 145 individuals were genotyped with eight polymorphic chloroplastic microsatellites, producing an average of 41 haplotypes with high genetic diversity across populations (H<sub>E</sub> = 0.90). Significant population genetic structure was found between populations (F<sub>ST</sub> = 0.123). These results reflect the impact of reforestation programs on natural populations and diluting the natural genetic signature. Analysis of population genetic data is, therefore, crucial for the breeding and conservation programs of <i>P. occidentalis</i> in the country.


2021 ◽  
pp. 76-96
Author(s):  
Alexander Likhachev

Natural materials and processes represent the global substance reflecting and determining its formation and existence as a whole and in all its components. Revealing the reasons for their formation and manifestation is crucial. The paper highlights the two main factors: «influences» and «gradients». Influences are interpreted as the impact of some substances and events on other similar parameters, and gradients are vector changes and differences in systems composition, structure, properties, states, energy and thermodynamic parameters. To provide an insight into the role and significance of the above factors and reasons, an attempt was made to consider their potential manifestation throughout the general world history within the existing knowledge about it.


2021 ◽  
Vol 2 (4) ◽  
pp. 21-43
Author(s):  
Daniel Debouck ◽  
Marcela Santaella ◽  
Luis Guillermo Santos

This work explains the reasons why a bean collection was established in 1973 at the International Center of Tropical Agriculture (CIAT) near Palmira in Colombia. It shows the impact of the collection on plant breeding and in agricultural development through the distribution of germplasm to the center’s bean breeding program, to successively find resistances to pests and diseases, adaptation to low phosphorus and drought, and more recently higher content of iron and zinc in seeds. The collection was also used to progress knowledge in biological sciences, as shown by a dozen of examples. A reason behind these successes was foresight and focus on diversity per se in the collection. The paper ends with a number of suggestions for the way ahead for the genetic resources conservation and management of these bean crops, and possible take-home lessons for curators in charge of other similar collections.


2018 ◽  
Author(s):  
Yanfen Zhao ◽  
Hongxiang Zhang ◽  
Borong Pan ◽  
Mingli Zhang

Climactic fluctuations during the Quaternary played a crucial role in genetic diversity and population genetic structure of many plant species in northwestern China. In order to understand the impact of climate change on herbaceous plants, we studied Panzerina lanata (Lamiaceae), a widely distributed species. Two chloroplast DNA intergenic spacers (trnH-psbA and rpoB-trnC) were used to sequence 269 individuals from 27 populations and seven haplotypes were identified. Genetic structure and demographic characteristics were estimated using AMOVA, neutrality tests, and mismatch distribution analyses. The divergence times between the seven haplotypes were estimated using Beast. Our results revealed high levels of total genetic diversity (HT = 0.673±0.0869) and low levels of average within-population genetic diversity (HS = 0.033±0.0214). The analysis of molecular variance indicated major genetic differentiation among the three groups: northern, central, and eastern group. The species distribution modeling and demographic analysis indicated that P. lanata has not experience a recent range expansion. The divergence time within P. lanata occurred between the early Pleistocene and the late Pleistocene, which coincides with aridification and the expansion of the deserts in northwestern China that resulted in species diversification and habitat fragmentation. In addition, we speculate that the deserts and the Helan Mountains acted as effective geographic barriers that led to intraspecific diversity.


1997 ◽  
Vol 34 (4) ◽  
pp. 473-484 ◽  
Author(s):  
France Leclerc ◽  
John D. C. Little

Packaged goods manufacturers distribute cents-off coupons in freestanding inserts (FSIs) in newspapers. Free-standing insert coupons are typically composed of two parts: the coupon per se and a print advertisement. Using two laboratory experiments and a separate analysis of coupon measurements from scanner panels, the authors investigate whether the content of the print advertisement influences the effectiveness of the coupon. Theoretical arguments suggest that the impact on consumer attitudes will depend on the executional cues of the copy, the brand loyalty of the consumers, and the consumer's involvement with the product category. The results support the theoretical framework and suggest that it is possible to make FSI coupons more effective by choosing appropriate executional cues for their advertising copy.


1999 ◽  
Vol 43 (4) ◽  
pp. 882-889 ◽  
Author(s):  
Philip D. Lister ◽  
Victoria M. Gardner ◽  
Christine C. Sanders

ABSTRACT Although previous studies have indicated that clavulanate may induce AmpC expression in isolates of Pseudomonas aeruginosa, the impact of this inducer activity on the antibacterial activity of ticarcillin at clinically relevant concentrations has not been investigated. Therefore, a study was designed to determine if the inducer activity of clavulanate was associated with in vitro antagonism of ticarcillin at pharmacokinetically relevant concentrations. By the disk approximation methodology, clavulanate induction of AmpC expression was observed with 8 of 10 clinical isolates of P. aeruginosa. Quantitative studies demonstrated a significant induction of AmpC when clavulanate-inducible strains were exposed to the peak concentrations of clavulanate achieved in human serum with the 3.2- and 3.1-g doses of ticarcillin-clavulanate. In studies with three clavulanate-inducible strains in an in vitro pharmacodynamic model, antagonism of the bactericidal effect of ticarcillin was observed in some tests with regimens simulating a 3.1-g dose of ticarcillin-clavulanate and in all tests with regimens simulating a 3.2-g dose of ticarcillin-clavulanate. No antagonism was observed in studies with two clavulanate-noninducible strains. In contrast to clavulanate, tazobactam failed to induce AmpC expression in any strains, and the pharmacodynamics of piperacillin-tazobactam were somewhat enhanced over those of piperacillin alone against all strains studied. Overall, the data collected from the pharmacodynamic model suggested that induction per se was not always associated with reduced killing but that a certain minimal level of induction by clavulanate was required before antagonism of the antibacterial activity of its companion drug occurred. Nevertheless, since clinically relevant concentrations of clavulanate can antagonize the bactericidal activity of ticarcillin, the combination of ticarcillin-clavulanate should be avoided when selecting an antipseudomonal β-lactam for the treatment of P. aeruginosa infections, particularly in immunocompromised patients. For piperacillin-tazobactam, induction is not an issue in the context of treating this pathogen.


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