Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
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Concept and history of genetic control

6014
Scott, M. J. and Benedict, M. Q.,  Genetic Control of Malaria and Dengue,  2:31-54. 2016-12-30 20:16:45.
Genetic control of insects is an established method, mainly for insects that are important crop and veterinary pests such as medflies and screwworm. Efforts to use the same technologies against insects of medical importance, especially mosquitoes, have had limited success. The successes against mosquitoes have been accomplished using forms of both conventional and modern methods, both of which are promising. In this chapter, we provide highlights of the development of genetic control of agricultural pests and describe how the development of methods against mosquitoes reflects those advances. While admiring successful genetic control programs is motivating, we suggest that much can also be learned from both past successful and failed efforts, as doing so will increase our ability to improve future activities.

National Academies hit the brakes on gene drive-modified organisms

5657
Abbasi, J.,  JAMA-Journal of the American Medical Association,  316:482-483. 2016-12-17 18:11:25.
Despite their potential for fighting Zika, malaria, and other public health scourges, organisms that have been engineered to quickly spread genetic modifications through a population—and possibly an entire species—are not ready for release into the wild, a committee of interdisciplinary experts concluded in a recent report by the National Academies of Sciences, Engineering, and Medicine (http://bit.ly/1UHuqQk). So-called gene drive–modified organisms “require more research in laboratories and highly controlled field trials,” the committee said in a statement (http://bit.ly/1tkWCTO). Gene drives are systems of “biased inheritance” that enhance a genetic element’s ability to pass from parent organism to offspring through sexual reproduction. These selfish genetic elements could be genes or their fragments, all or parts of chromosomes, or noncoding DNA, the report stated.

Invertebrate Biosecurity Challenges in High-Productivity Grassland: The New Zealand Example

13738
S. L. Goldson, B. I. P. Barratt and K. F. Armstrong,  Frontiers in Plant Science,  7. 2016-11-15 19:35:24.
This review explores the unique challenges faced by pasture biosecurity and what may be done to confront existing difficulties. While there is no silver bullet, and limited opportunity pre and at for improving pasture biosecurity, advancement may include increased and informed vigilance by farmers, pheromone traps and resistant plants to slow invasion. Increasingly, there is also the potential for more use of improved population dispersal models and surveillance strategies including unmanned aerial vehicles, as well as emerging techniques to determine invasive pest genomes and their geographical origins.

Mitonuclear interactions, mtDNA-mediated thermal plasticity, and implications for the Trojan Female Technique for pest control

13745
J. N. Wolff, D. M. Tompkins, N. J. Gemmell and D. K. Dowling,  Scientific Reports,  6. 2016-07-21 19:45:17.
Here we test whether the male-sterilizing effects previously associated with the mt: Cyt-b mutation are consistent across three thermal and three nuclear genomic contexts. The effects of this mutation were indeed moderated by the nuclear background and thermal environment, but crucially the fertility of males carrying the mutation was invariably reduced relative to controls. This mutation thus constitutes a promising candidate for the further development of the TFT.

Prospects and challenges of CRISPR/Cas genome editing for the study and control of neglected vector-borne nematode diseases

6017
M. Zamanian and E. C. Andersen,  The FEBS Journal,  283:3204-3221. 2016-06-14 20:22:18.
Neglected tropical diseases caused by parasitic nematodes inflict an immense health and socioeconomic burden throughout much of the developing world. Current estimates indicate that more than two billion people are infected with nematodes, resulting in the loss of 14 million disability-adjusted life years per annum. Although these parasites cause significant mortality, they primarily cause chronic morbidity through a wide range of severe clinical ailments. Treatment options for nematode infections are restricted to a small number of anthelmintic drugs, and the rapid expansion of anthelmintic mass drug administration raises concerns of drug resistance. Preservation of existing drugs is necessary, as well as the development of new treatment options and methods of control. We focus this review on how the democratization of CRISPR/Cas9 genome editing technology can be enlisted to improve our understanding of the biology of nematode parasites and our ability to treat the infections they cause. We will first explore how this robust method of genome manipulation can be used to newly exploit the powerful model nematode Caenorhabditis elegans for parasitology research. We will then discuss potential avenues to develop CRISPR/Cas9 editing protocols in filarial nematodes. Lastly, we will propose potential ways in which CRISPR/Cas9 can be used to engineer gene drives that target the transmission of mosquito-borne filarial nematodes.

Lethal Gene Drive Selects Inbreeding

13627
J. J. Bull,  bioRxiv,  046847. 2016-06-03 13:55:41.
ere, population genetic models are used to consider the evolution of inbreeding (specifically selfing) as a possible response to a recessively lethal HEG with complete segregation distortion. Numerical analyses indicate a rich set of outcomes, but selfing often evolves in response to the HEG, with a corresponding partial restoration of mean fitness. Whether selfing does indeed evolve and its effect in restoring fitness depends heavily on the magnitude of inbreeding depression. Overall, these results point toward an underappreciated evolutionary response to block the harmful effects of a selfish gene.

Mating competitiveness of sterile genetic sexing strain males (GAMA) under laboratory and semi-field conditions: Steps towards the use of the Sterile Insect Technique to control the major malaria vector Anopheles arabiensis in South Africa

25911
G. Munhenga, B. D. Brooke, J. R. L. Gilles, K. Slabbert, A. Kemp, L. C. Dandalo, O. R. Wood, L. N. Lobb, D. Govender, M. Renke and L. L. Koekemoer,  Parasites and Vectors,  9:122. 2016-03-02 13:00:23.
Anopheles arabiensis Patton is primarily responsible for malaria transmission in South Africa after successful suppression of other major vector species using indoor spraying of residual insecticides. Control of An. arabiensis using current insecticide based approaches is proving difficult owing to the development of insecticide resistance, and variable feeding and resting behaviours. The use of the sterile insect technique as an area-wide integrated pest management system to supplement the control of An. arabiensis was proposed for South Africa and is currently under investigation. The success of this technique is dependent on the ability of laboratory-reared sterile males to compete with wild males for mates. As part of the research and development of the SIT technique for use against An. arabiensis in South Africa, radio-sensitivity and mating competitiveness of a local An. arabiensis sexing strain were assessed.

Engineering the wild: Gene drives and intergenerational equity

6948
J. Kuzma and L. Rawls,  Jurimetrics,  56:279-296. 2016-03-01 16:08:02.
New genetic engineering methods are allowing scientists to insert genes into organisms that have the potential to spread themselves throughout natural populations upon the release of individuals carrying those genes. Gene drive technology is being researched and developed for purposes of reducing or eliminating human, ecological or agricultural pest populations, or immunizing other desirable or endangered species against pests and disease. The ability of humans to alter populations within ecosystems through genetic engineering raises issues associated with biodiversity and conservation that, in turn, may affect the abilities of current and future generations to use and enjoy the benefits of the natural world. Yet, children and future generations are not typically given voice in legal, policy, or ethical debates. This article examines several of the intergenerational equity issues posed by gene drive technologies. A typology of gene drive purposes and their potential ecological impacts is developed, followed by an examination of how they may intersect with concerns about intergenerational equity. To our knowledge, this analysis is the first to explore human intervention through genetically engineering populations in the wild and the impacts on future generations

Cheating evolution: engineering gene drives to manipulate the fate of wild populations

4083
Champer, JB, A.; Akbari, O. S.,  Nature Reviews Genetics,  17:146-159. 2016-01-21 00:00:00.
Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne diseases such as malaria. Although several types of selfish genetic elements exist in nature, few have been successfully engineered in the laboratory thus far. With the discovery of RNA-guided CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated 9) nucleases, which can be utilized to create, streamline and improve synthetic gene drives, this is rapidly changing. Here, we discuss the different types of engineered gene drives and their potential applications, as well as current policies regarding the safety and regulation of gene drives for the manipulation of wild populations.

No evidence for female discrimination against male house mice carrying a selfish genetic element

4103
Sutter, AL, A. K.,  Current Zoology,  62:675-685. 2016-01-21 00:00:00.
Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous (+/t) mice leads to high embryo mortality. Previous experiments showing that +/t females avoid this incompatibility cost by preferring +/+versus +/t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against +/t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between gametes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by +/t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.

Genome editing: intellectual property and product development in plant biotechnology

4102
Schinkel, HS, S.,  Plant Cell Reports,  35:1487-1491. 2016-01-20 00:00:00.
Genome editing is a revolutionary technology in molecular biology. While scientists are fascinated with the unlimited possibilities provided by directed and controlled changes in DNA in eukaryotes and have eagerly adopted such tools for their own experiments, an understanding of the intellectual property (IP) implications involved in bringing genome editing-derived products to market is often lacking. Due to the ingenuity of genome editing, the time between new product conception and its actual existence can be relatively short; therefore knowledge about IP of the various genome editing methods is relevant. This point must be regarded in a national framework as patents are instituted nationally. Therefore, when designing scientific work that could lead to a product, it is worthwhile to consider the different methods used for genome editing not only for their scientific merits but also for their compatibility with a speedy and reliable launch into the desired market.

Marcus Rhoades on preferential segregation in maize

4082
Birchler, JA,  Genetics,  203:1489-1490. 2016-01-20 00:00:00.
Rhoades was studying a variant form of chromosome 10 with a conspicuous abnormality; it carried extensive heterochromatin at the tip of the long arm. This variant had been found by Albert Longley in indigenous maize varieties from the southwestern United States and provided to Rhoades for the pedestrian task of determining the recombination frequency between the anthocyanin pigment gene, R, and the end of the chromosome. The abnormal chromosome 10 originally carried the recessive, r, allele (colorless kernels) and was crossed to other lines carrying the dominant R (red kernels). Much to the surprise of Rhoades, when these heterozygotes were testcrossed with the recessive, there was a strong skew from a 1:1 ratio. Rather than the roughly even mix of colorless and red kernels that he expected, around two-thirds were colorless. This excess of r alleles was caused by linkage to the variant chromosome; in the few progeny that transferred the dominant R allele to the abnormal chromosome 10, subsequent testcrosses demonstrated that it was now the dominant allele that was preferentially inherited.

Gene drive through a landscape: Reaction-diffusion models of population suppression and elimination by a sex ratio distorter

4081
Beaghton, AB, P. J.; Burt, A.,  Theoretical Population Biology,  108:51-69. 2016-01-19 00:00:00.
Some genes or gene complexes are transmitted from parents to offsprihg at a greater-than-Mendelian rate, and can spread and persist in populations even if they cause some harm to the individuals carrying them. Such genes may be useful for controlling populations or species that are harmful. Driving-Y chromosomes may be particularly potent in this regard, as they produce a male-biased sex ratio that, if sufficiently extreme, can lead to population elimination. To better understand the potential of such genes to spread over a landscape, we have developed a series of reaction-diffusion models of a driving-Y chromosome in 1-D and radially-symmetric 2-D unbounded domains. The wild-type system at carrying capacity is found to be unstable to the introduction of driving-Y males for all models investigated. Numerical solutions exhibit travelling wave pulses and fronts, and analytical and semi-analytical solutions for the asymptotic wave speed under bounded initial conditions are derived. The driving-Y male invades the wild-type equilibrium state at the front of the wave and completely replaces the wild-type males, leaving behind, at the tail of the wave, a reduced- or zero-population state of females and driving-Y males only. In our simplest model of a population with one life stage and density-dependent mortality, wave speed depends on the strength of drive and the diffusion rate of Y-drive males, and is independent of the population dynamic consequences (suppression or elimination). Incorporating an immobile juvenile stage of fixed duration into the model reduces wave speed approximately in proportion to the relative time spent as a juvenile. If females mate just once in their life, storing sperm for subsequent reproduction, then wave speed depends on the movement of mated females as well as Y-drive males, and may be faster or slower than in the multiple-mating model, depending on the relative duration of juvenile and adult life stages. Numerical solutions are shown for parameter values that may in part be representative for Anopheles gambiae, the primary vector of malaria in sub-Saharan Africa. (C) 2015 The Authors. Published by Elsevier Inc.

Random and non-random mating populations: Evolutionary dynamics in meiotic drive

4101
Sarkar, B,  Mathematical Biosciences,  271:29-41. 2016-01-19 00:00:00.
Game theoretic tools are utilized to analyze a one-locus continuous selection model of sex-specific meiotic drive by considering nonequivalence of the viabilities of reciprocal heterozygotes that might be noticed at an imprinted locus. The model draws attention to the role of viability selections of different types to examine the stable nature of polymorphic equilibrium. A bridge between population genetics and evolutionary game theory has been built up by applying the concept of the Fundamental Theorem of Natural Selection. In addition to pointing out the influences of male and female segregation ratios on selection, configuration structure reveals some noted results, e.g., Hardy-Weinberg frequencies hold in replicator dynamics, occurrence of faster evolution at the maximized variance fitness, existence of mixed Evolutionarily Stable Strategy (ESS) in asymmetric games, the tending evolution to follow not only a 1:1 sex ratio but also a 1:1 different alleles ratio at particular gene locus. Through construction of replicator dynamics in the group selection framework, our selection model introduces a redefining bases of game theory to incorporate non-random mating where a mating parameter associated with population structure is dependent on the social structure. Also, the model exposes the fact that the number of polymorphic equilibria will depend on the algebraic expression of population structure. (C) 2015 Elsevier Inc. All rights reserved.

Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome

4100
Rydzewski, WTC, S. A.; Lievano, G.; Lynch, V. D.; Patten, M. M.,  Journal of Evolutionary Biology,  29:1247-1256. 2016-01-18 00:00:00.
Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, D-z('), which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome.

Target Malaria has a killer in its sights: Eliminating the world’s deadliest disease has been a priority for decades, and, thanks to innovative gene-drive technology, Target Malaria is getting closer to achieving that goal

4080
Banks, J,  IEEE Pulse,  7:30-33. 2016-01-18 00:00:00.
The mosquito is the deadliest animal in the world (Figure 1). It is the main carrier of parasites that cause malaria, which is a bigger killer than any other disease in history; in fact, some blame malaria for the deaths of half the humans who have ever lived. Today, malaria continues to have a devastating effect on the health of millions of people.

Genetic engineering to eradicate invasive mice on islands: modeling the efficiency and ecological impacts

4079
Backus, GAG, K.,  Ecosphere,  7:e01589. 2016-01-17 00:00:00.
Invasive rodents are usually eradicated from islands through the application of chemical toxicants that can harm surrounding ecosystems. A recently proposed alternative involves engineering a house mouse (Mus musculus) to carry a genetic construct that would cause a majority of its offspring to be male, many of which would be sterile. Releasing these genetically engineered mice to interbreed with an invasive population would reduce the number of fertile female mice until no more remain. We constructed a mathematical model to analyze the population dynamics of eradication with this genetically engineered mouse and determined its eradication efficiency through model analysis and simulations. Because genetically engineered mice would likely have a fitness disadvantage compared to wild mice, we found that they would need to be repeatedly released into the population to ensure complete eradication. However, if genetically engineered mice have a substantial survival advantage, we determined that the genetic construct could theoretically spread and eradicate a population after a single pulsed release onto the target island or after an engineered mouse escapes to a non-target location. Also, while the species specificity of genetic engineering avoids some of the non-target impacts of traditional eradication methods, ecological impacts could manifest indirectly. We compared several metrics to estimate potential transient impacts on the ecosystem and found that there is a trade-off between the speed of an eradication and the intensity of increased disruptive ecological interactions. Together, our results can inform safe and efficient ecological practices for eradication with developing genetic engineering technology.

Intragenomic conflict produces sex ratio dynamics that favor maternal sex ratio distorters

4099
Rood, ESF, S.,  Ecology and Evolution,  6:8085-8093. 2016-01-17 00:00:00.
Maternal sex ratio distorters (MSDs) are selfish elements that enhance their transmission by biasing their host's sex allocation in favor of females. While previous models have predicted that the female-biased populations resulting from sex ratio distortion can benefit from enhanced productivity, these models neglect Fisherian selection for nuclear suppressors, an unrealistic assumption in most systems. We used individual-based computer simulation modeling to explore the intragenomic conflict between sex ratio distorters and their suppressors and explored the impacts of these dynamics on population-level competition between species characterized by MSDs and those lacking them. The conflict between distorters and suppressors was capable of producing large cyclical fluctuations in the population sex ratio and reproductive rate. Despite fitness costs associated with the distorters and suppressors, MSD populations often exhibited enhanced productivity and outcompeted non-MSD populations in single and multiple-population competition simulations. Notably, the conflict itself is beneficial to the success of populations, as sex ratio oscillations limit the competitive deficits associated with prolonged periods of male rarity. Although intragenomic conflict has been historically viewed as deleterious to populations, our results suggest that distorter-suppressor conflict can provide population-level advantages, potentially helping to explain the persistence of sex ratio distorters in a range of taxa.

A meiotic drive element in the maize pathogen Fusarium verticillioides is located within a 102 kb region of chromosome V

4098
Pyle, JP, T.; Merrill, B.; Nsokoshi, C.; McCall, M.; Proctor, R. H.; Brown, D. W.; Hammond, T. M.,  G3-Genes Genomes Genetics,  6:2543-2552. 2016-01-16 00:00:00.
Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (Sk(K)) that causes nearly all surviving meiotic progeny from an Sk(K) x Spore killer-susceptible (Sk(S)) cross to inherit the Sk(K) allele. Sk(K) has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an Sk(K) x Sk(S) mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of Sk(K) to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to Sk(S) genotypes, Sk(K) genotypes have one extra gene within this region for a total of 42 genes. The additional gene in Sk(K) genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hyper-variable regions, the longest of which includes SKC1. The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed.

Selfish genetic elements and the gene’s-eye view of evolution

4078
Ågren, JA,  Current Zoology,  62:659-665. 2016-01-16 00:00:00.
During the last few decades, we have seen an explosion in the influx of details about the biology of selfish genetic elements. Ever since the early days of the field, the gene’s-eye view of Richard Dawkins, George Williams, and others, has been instrumental to make sense of new empirical observations and to the generation of new hypotheses. However, the close association between selfish genetic elements and the gene’s-eye view has not been without critics and several other conceptual frameworks have been suggested. In particular, proponents of multilevel selection models have used selfish genetic elements to criticize the gene’s-eye view. In this paper, I first trace the intertwined histories of the study of selfish genetic elements and the gene’s-eye view and then discuss how their association holds up when compared with other proposed frameworks. Next, using examples from transposable elements and the major transitions, I argue that different models highlight separate aspects of the evolution of selfish genetic elements and that the productive way forward is to maintain a plurality of perspectives. Finally, I discuss how the empirical study of selfish genetic elements has implications for other conceptual issues associated with the gene’s-eye view, such as agential thinking, adaptationism, and the role of fitness maximizing models in evolution.

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