scholarly journals Gene drives and population persistence vs elimination: the impact of spatial structure and inbreeding at low density

2021 ◽  
Author(s):  
Pantelis John Beaghton ◽  
Austin Burt
Keyword(s):  
Inbreeding Depression ◽  
Essential Gene ◽  
Random Mating ◽  
Critical Role ◽  
Target Population ◽  
Low Density ◽  
Pest Species ◽  
Allee Effects ◽  
Gene Drive ◽  
The Impact

Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.

scholarly journals Double drives and private alleles for localised population genetic control

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009333
Author(s):  
Katie Willis ◽  
Austin Burt
Keyword(s):  
Genetic Control ◽  
Population Genetic ◽  
Genomic Analysis ◽  
Target Population ◽  
Pest Species ◽  
Gene Drive ◽  
Population Replacement ◽  
Target Populations ◽  
Control Disease ◽  
Alternative Designs

Synthetic gene drive constructs could, in principle, provide the basis for highly efficient interventions to control disease vectors and other pest species. This efficiency derives in part from leveraging natural processes of dispersal and gene flow to spread the construct and its impacts from one population to another. However, sometimes (for example, with invasive species) only specific populations are in need of control, and impacts on non-target populations would be undesirable. Many gene drive designs use nucleases that recognise and cleave specific genomic sequences, and one way to restrict their spread would be to exploit sequence differences between target and non-target populations. In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of CRISPR PAM sites in island and mainland populations of the malaria mosquitoAnopheles gambiaeindicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.

scholarly journals Bioeconomic synergy between tactics for insect eradication in the presence of Allee effects

2012 ◽  
Vol 279 (1739) ◽  
pp. 2807-2815 ◽  
Author(s):  
Julie C. Blackwood ◽  
Ludek Berec ◽  
Takehiko Yamanaka ◽  
Rebecca S. Epanchin-Niell ◽  
Alan Hastings ◽  
...  
Keyword(s):  
Native Species ◽  
Mating Disruption ◽  
Cost Effective ◽  
Small Populations ◽  
Low Density ◽  
Pest Species ◽  
Allee Effects ◽  
Pesticide Application ◽  
Simultaneous Application

Preventing the establishment of invading pest species can be beneficial with respect to averting future environmental and economic impacts and also in preventing the accumulation of control costs. Allee effects play an important role in the dynamics of newly established, low-density populations by driving small populations into self-extinction, making Allee effects critical in influencing outcomes of eradication efforts. We consider interactions between management tactics in the presence of Allee effects to determine cost-effective and time-efficient combinations to achieve eradication by developing a model that considers pesticide application, predator augmentation and mating disruption as control tactics, using the gypsy moth as a case study. Our findings indicate that given a range of constant expenditure levels, applying moderate levels of pesticides in conjunction with mating disruption increases the Allee threshold which simultaneously substantially decreases the time to eradication relative to either tactic alone. In contrast, increasing predation in conjunction with other tactics requires larger economic expenditures to achieve similar outcomes for the use of pesticide application or mating disruption alone. These results demonstrate the beneficial synergy that may arise from nonlinearities associated with the simultaneous application of multiple eradication tactics and offer new prospects for preventing the establishment of damaging non-native species.

scholarly journals Controlling invasive rodents via synthetic gene drive and the role of polyandry

2019 ◽  
Vol 286 (1909) ◽  
pp. 20190852 ◽  
Author(s):  
Andri Manser ◽  
Stephen J. Cornell ◽  
Andreas Sutter ◽  
Dimitri V. Blondel ◽  
Megan Serr ◽  
...  
Keyword(s):  
Target Population ◽  
Natural Setting ◽  
Pest Species ◽  
Gene Drive ◽  
Island Ecosystems ◽  
Control Programmes ◽  
Potential Pest ◽  
Invasive Rodents ◽  
Native Invasive

House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male’s sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three- to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.

scholarly journals Double drives and private alleles for localised population genetic control

2021 ◽  
Author(s):  
Katie Willis ◽  
Austin Burt
Keyword(s):  
Genetic Control ◽  
Population Genetic ◽  
Genomic Analysis ◽  
Target Population ◽  
Pest Species ◽  
Gene Drive ◽  
Population Replacement ◽  
Target Populations ◽  
Mosquito Anopheles Gambiae ◽  
Control Disease

Synthetic gene drive constructs could, in principle, provide the basis for highly efficient interventions to control disease vectors and other pest species. This efficiency derives in part from leveraging natural processes of dispersal and gene flow to spread the construct and its impacts from one population to another. However, sometimes (for example, with invasive species) only specific populations are in need of control, and impacts on non-target populations would be undesirable. Many gene drive designs use nucleases that recognise and cleave specific genomic sequences, and one way to restrict their spread would be to exploit sequence differences between target and non-target populations. In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of PAM sites in island and mainland populations of the malaria mosquito Anopheles gambiae indicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

F117EVALUATING THE IMPACT OF NON-RANDOM MATING: PSYCHIATRIC OUTCOMES AMONG THE OFFSPRING OF PAIRS DIAGNOSED WITH SCHIZOPHRENIA AND BIPOLAR DISORDER

2019 ◽  
Vol 29 ◽  
pp. S1173-S1174
Author(s):  
James Crowley ◽  
Ashley Nordsletten ◽  
Gustaf Brander ◽  
Patrick Sullivan ◽  
Naomi Wray ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Random Mating ◽  
Psychiatric Outcomes ◽  
The Impact

scholarly journals The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

2021 ◽  
Author(s):  
Valentin Sencio ◽  
Marina Gomes Machado ◽  
François Trottein
Keyword(s):  
Gut Microbiota ◽  
Bacterial Infections ◽  
Respiratory Infections ◽  
Critical Role ◽  
Good Health ◽  
Disease Outcomes ◽  
And Function ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Viral Respiratory

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

scholarly journals Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats

2021 ◽  
Vol 22 (9) ◽  
pp. 4961
Author(s):  
Maria Kovalska ◽  
Eva Baranovicova ◽  
Dagmar Kalenska ◽  
Anna Tomascova ◽  
Marian Adamkov ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Brain Area ◽  
Critical Role ◽  
Cerebrovascular Diseases ◽  
Behavioral Pattern ◽  
Cell Physiology ◽  
Male Wistar Rats ◽  
High Level ◽  
Hippocampal Alterations ◽  
The Impact

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Trends in genetic diversity and the effect of inbreeding in American Angus cattle under genomic selection

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Emmanuel A. Lozada-Soto ◽  
Christian Maltecca ◽  
Duc Lu ◽  
Stephen Miller ◽  
John B. Cole ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Beef Cattle ◽  
Genomic Selection ◽  
Inbreeding Depression ◽  
Growth Traits ◽  
Effective Population ◽  
Angus Cattle ◽  
Genomic Inbreeding ◽  
Chromosome Segments ◽  
The Impact

Abstract Background While the adoption of genomic evaluations in livestock has increased genetic gain rates, its effects on genetic diversity and accumulation of inbreeding have raised concerns in cattle populations. Increased inbreeding may affect fitness and decrease the mean performance for economically important traits, such as fertility and growth in beef cattle, with the age of inbreeding having a possible effect on the magnitude of inbreeding depression. The purpose of this study was to determine changes in genetic diversity as a result of the implementation of genomic selection in Angus cattle and quantify potential inbreeding depression effects of total pedigree and genomic inbreeding, and also to investigate the impact of recent and ancient inbreeding. Results We found that the yearly rate of inbreeding accumulation remained similar in sires and decreased significantly in dams since the implementation of genomic selection. Other measures such as effective population size and the effective number of chromosome segments show little evidence of a detrimental effect of using genomic selection strategies on the genetic diversity of beef cattle. We also quantified pedigree and genomic inbreeding depression for fertility and growth. While inbreeding did not affect fertility, an increase in pedigree or genomic inbreeding was associated with decreased birth weight, weaning weight, and post-weaning gain in both sexes. We also measured the impact of the age of inbreeding and found that recent inbreeding had a larger depressive effect on growth than ancient inbreeding. Conclusions In this study, we sought to quantify and understand the possible consequences of genomic selection on the genetic diversity of American Angus cattle. In both sires and dams, we found that, generally, genomic selection resulted in decreased rates of pedigree and genomic inbreeding accumulation and increased or sustained effective population sizes and number of independently segregating chromosome segments. We also found significant depressive effects of inbreeding accumulation on economically important growth traits, particularly with genomic and recent inbreeding.

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