Keywords: Genetics

Drive, suppression and escape from suppression of a selfish chromosome

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Jackson Ridges, Jackson Bladen, Robert Unckless, Nitin Phadnis,  Proc Biol Sci,  21. 2026-01-21 13:39:59.
Meiotic drivers are selfish genetic elements that are predicted to spark rapid intra-genomic arms races with their suppressors. However, the long-term persistence of unsuppressed selfish chromosomes in natural populations violates these theoretical expectations. The Drosophila pseudoobscura Sex-Ratio (SR) chromosome exemplifies this problem, sometimes referred to as the ‘ancient gene drive paradox’. Here, we analyse the evolutionary history of this SR chromosome and show that its genetic architecture and complexity have likely been shaped by a history of drive, suppression and escape from suppression. Our results suggest that the current lack of resistance to the SR chromosome may represent a transient condition awaiting the emergence of new suppressors.

Influence of genetic factors of humans, mosquitoes and parasites, on the evolution of Plasmodium falciparum infections, malaria transmission and genetic control methods: a review of the literature

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Nikiema, S., Soulama, I., Ampofo, G.D. et al.,  BMC Medical Genomics,  18. 2025-06-06 08:52:12.
Despite significant progress, malaria remains a public health problem in many regions, particularly in sub-Saharan Africa. This situation is partly explained by the mosquito’s resistance to insecticides and the emergence of parasite resistance to antimalarial drugs. Indeed, in spite of the various vectors’ controls, insecticide resistance emerges from multi-generational selection and poses worldwide concern. In parallel, artemisinin resistance unfortunately emerged independently in multiple countries in eastern Africa. Since 2014, artemisinin resistance has been observed in 6 countries in Africa and, more concerningly, the evidence from longitudinal molecular surveys in these countries suggests that it is spreading. While phenotypic evidence of treatment failure is still limited, the increasing reports of validated artemisinin resistance mutations are alarming. Unlike the emergence of artemisinin resistance in South-East Asia, our understanding of the genetic determinants of artemisinin resistance and our ability to sequence and map the spread of resistance are significantly greater. In addition to mosquito and parasite genetics affecting malaria evolution, many human individual variants have been identified that are associated with malaria protection, but the most important of all relates to the structure or function of red blood cells, the classical polymorphisms that causes sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. In that biological complex context, there is a need to characterize the various genetic factors in Plasmodium falciparum, humans and mosquitoes that are potentially associated with resistance to antimalarial drugs and insecticides, and their involvement in the evolution, severity and transmission of malaria. In this direction, A comprehensive literature review was conducted to capture the objectives highlighted above. The advances in genomic surveillance and emerging genetic control strategies, such as gene drive technology were also considered in this review. We used search engines such as PubMed and Google scholar to retrieve articles useful to the objective of this paper and information on the knowledge of genetic factors and methods that contributed to malaria control were synthesized.

Reenacting a mouse genetic evolutionary arms race in yeast reveals that SLXL1/SLX compete with SLY1/2 for binding to Spindlins

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M.F. Arlt,A.N. Kruger,C.M. Swanepoel,& J.L. Mueller,  Proceedings of the National Academy of Sciences,  122. 2025-03-04 10:54:14.
In the house mouse, an evolutionary arms race between proteins encoded by the X-linked Slxl1/Slx and Y-linked Sly gene families during spermatogenesis can distort offspring sex ratio, but how these proteins compete remains unknown. We report how SLXL1/SLX competes with SLY1/SLY2 by demonstrating their dose-dependent competitive binding to Spindlins, the key protein domains and rapidly evolving residues and exons that drive the competition, and how the competition is likely between complex multimers. Our findings have broad implications for the mechanics of evolutionary arms and how competition between sex chromosomes influences X- versus Y-sperm fitness and sex ratio.

The Meiotic Drive: Intragenomic Competition and Selection

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I. A. Zakharov,  Russian Journal of Genetics,  60:1311-1318. 2024-11-12 12:02:24.
The article considers the distribution and mechanisms of the meiotic drive as a phenomenon manifested in unequal transmission of gene alleles and/or homologous chromosomes into gametes during meiosis. The meiotic drive has been studied in the most detail in Drosophila, mice, corn, and ascomycete fungi of the genera Neurospora and Podospora. The consequence of the meiotic drive is a shift in the frequencies of alleles in the gene pool and the maintenance of nonadaptive traits in the population.

Functional and evolutionary constraints of wtf killer meiotic drivers

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Ananya Nidamangala Srinivasa, Samuel Campbell, Shriram Venkatesan, Nicole L Nuckolls, Jeffrey J Lange, Randal Halfmann, Sarah E Zanders,  bioRxiv,  2024-08-29 10:38:59.
Killer meiotic drivers are selfish DNA loci that sabotage the gametes that do not inherit them from a driver+/driver- heterozygote. These drivers often employ toxic proteins that target essential cellular functions to cause the destruction of driver- gametes. Identifying the mechanisms of drivers can expand our understanding of infertility and reveal novel insights about the cellular functions targeted by drivers. In this work, we explore the molecular mechanisms underlying the wtf family of killer meiotic drivers found in fission yeasts. Each wtf killer acts using a toxic Wtfpoison protein that can be neutralized by a corresponding Wtfantidote protein. The wtf genes are rapidly evolving and extremely diverse. Here we found that self-assembly of Wtfpoison proteins is broadly conserved and associated with toxicity across the gene family, despite minimal amino acid conservation. In addition, we found the toxicity of Wtfpoison assemblies can be modulated by protein tags designed to increase or decrease the extent of the Wtfpoison assembly, implicating assembly size in toxicity. We also identified a conserved, critical role for the specific co-assembly of the Wtfpoison and Wtfantidote proteins in promoting effective neutralization of Wtfpoison toxicity. Finally, we engineered wtf alleles that encode toxic Wtfpoison proteins that are not effectively neutralized by their corresponding Wtfantidote proteins. The possibility of such self-destructive alleles reveals functional constraints on wtf evolution and suggests similar alleles could be cryptic contributors to infertility in fission yeast populations. As rapidly evolving killer meiotic drivers are widespread in eukaryotes, analogous self-killing drive alleles could contribute to sporadic infertility in many lineages.

Researchers develop plant gene drive system for enhanced trait inheritance

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Anonymous,  Scientific Inquirer,  2024-07-25 20:23:52.
A collaborative research team led by QIAN Wenfeng from the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences and Peking University has developed a plant gene drive system called CRISPR-Assisted Inheritance utilizing NPG1 (CAIN), which, according to the researchers, uses a toxin-antidote mechanism in the male germline to override Mendelian inheritance in plants. Their findings were published in Nature Plants. In nature, gene inheritance typically follows Mendel’s laws, which provide an equal chance for alleles to pass on to the next generation—a cornerstone of Darwinian natural selection. However, super-Mendelian inheritance allows certain genes to be inherited at rates greater than the expected 50%, potentially allowing these genes to spread through populations even if they are detrimental to organisms. This mechanism opens the door to manipulating natural populations by introducing alleles that benefit humans even if they harm plant organisms themselves, or to eliminating species that are considered detrimental to human interests.

Escalation of genome defense capacity enables control of an expanding meiotic driver

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Peiwei Chen, Katherine C. Pan, Eunice H. Park, Yicheng Luo, Yuh Chwen G. Lee, Alexei A. Aravin,  bioRxiv,  2024-07-02 12:14:34.
From RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity1,2. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, which controls selfish elements in the metazoan germline, diverse target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases via enzymatic cleavage1,3. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via the innovation of new specificity factors4,5. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to the evolution of specificity factors, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the defense capacity of the piRNA pathway to control a recently expanded selfish gene in Drosophila melanogaster. Through an in vivo RNAi screen for repressors of Stellate—a recently evolved and expanded selfish meiotic driver6–8—we discovered a novel defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to drastically elevate Aub and AGO3 expression in the D. melanogaster lineage, thereby escalating the silencing capacity of the piRNA pathway to control expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life9–12, we envision that augmenting the defense capacity to quantitatively match selfish genes is likely a repeatedly employed defense strategy in evolution.

Editorial overview: Conflicts, conflicts everywhere

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Harmit S Malik, Judith E Mank,  Current Opinion in Genetics and Development,  83. 2023-12-31 20:20:14.
Genetic conflicts are pervasive in biology. They arise when genes, sets of genes, or chromosomes enhance their success at significant cost to their genetic neighbors. In some cases, conflicts occur when a ‘cheater’ subverts the rules of genetic inheritance, pitting the interests of the ‘cheater’ against the rest of the genome. In other cases, genetic elements play by the rules of genetic inheritance, but benefit some members of a species at the same time that they harm others. In this issue, we invited a group of scientists at the forefront of the study of different forms of genetic conflicts to share their expertise on some especially intriguing genetic battlegrounds, reflect on their historical underpinnings, summarize current advances, and discuss ideas that will propel the field forward in the years to come. Each of these tales of genetic conflicts is also a tale of evolutionary innovation. Some cases of conflict result from the unique opportunities created by nonfoolproof inheritance rules (e.g. the battle for transmission through gametes or the uniparental inheritance of mitochondria). In other cases, the ‘cheating’ elements (e.g. germline-restricted chromosomes (GRCs)) maintain themselves by creating opportunities to bypass rules their genetic neighbors are forced to abide by. Some conflicts thrive by imposing minimal costs on their neighbors, or even forcing a resolution of conflict so that the interests of all parties are accommodated within the genome. In contrast, others indulge in near-complete chromosomal or gametic fratricide, an observation that is difficult to reconcile without invoking genetic conflicts.

A population modification gene drive targeting both Saglin and Lipophorin impairs Plasmodium transmission in Anopheles mosquitoes

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Emily I Green, Etienne Jaouen, Dennis Klug, Roenick Proveti Olmo, Amandine Gautier, Stéphanie Blandin, Eric Marois,  eLife,  12. 2023-12-06 11:55:36.
Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.

Attempts to use breeding approaches in Aedes aegypti to create lines with distinct and stable relative Wolbachia densities

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A. J. Mejia, L. Jimenez, H. L. C. Dutra, R. Perera and E. A. McGraw,  Heredity,  2022-07-22 10:12:25.
Wolbachia is an insect endosymbiont being used for biological control in the mosquito Aedes aegypti because it causes cytoplasmic incompatibility (CI) and limits viral replication of dengue, chikungunya, and Zika viruses. While the genetic mechanism of pathogen blocking (PB) is not fully understood, the strength of both CI and PB are positively correlated with Wolbachia densities in the host. Wolbachia densities are determined by a combination of Wolbachia strain and insect genotype, as well as interactions with the environment. We employed both artificial selection and inbreeding with the goal of creating lines of Ae. aegypti with heritable and distinct Wolbachia densities so that we might better dissect the mechanism underlying PB. We were unable to shift the mean relative Wolbachia density in Ae. aegypti lines by either strategy, with relative densities instead tending to cycle over a narrow range. In lieu of this, we used Wolbachia densities in mosquito legs as predictors of relative densities in the remaining individual’s carcass. Because we worked with outbred mosquitoes, our findings indicate either a lack of genetic variation in the mosquito for controlling relative density, natural selection against extreme densities, or a predominance of environmental factors affecting densities. Our study reveals that there are moderating forces acting on relative Wolbachia densities that may help to stabilize density phenotypes post field release. We also show a means to accurately bin vector carcasses into high and low categories for non-DNA omics-based studies of Wolbachia-mediated traits.

The origin of island populations of the African malaria mosquito, Anopheles coluzzii

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M. Campos, M. Hanemaaijer, H. Gripkey, T. C. Collier, Y. S. Lee, A. J. Cornel, J. Pinto, D. Ayala, H. Rompao and G. C. Lanzaro,  Communications Biology,  4:9. 2021-05-26 10:26:11.
Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome study of 142 specimens from nine countries in continental Africa and three islands in the Gulf of Guinea. This sample set covers a large part of this species' geographic range. Our population genomic analyses included a description of the structure of mainland populations, island populations, and connectivity between them. Three genetic clusters are identified among mainland populations and genetic distances (F-ST) fits an isolation-by-distance model. Genomic analyses are applied to estimate the demographic history and ancestry for each island. Taken together with the unique biogeography and history of human occupation for each island, they present a coherent explanation underlying levels of genetic isolation between mainland and island populations. We discuss the relationship of our findings to the suitability of Sao Tome and Principe islands as candidate sites for potential field trials of genetic-based malaria control strategies. Campos, Lanzaro and colleagues use whole-genome sequencing and population genomic analyses to infer connectivity between mainland and island mosquito populations in West Africa. The unique biogeographic history for each island population is reported, and the findings highlight potential candidate sites for genetic-based malaria control strategies.

Selfish chromosomal drive shapes recent centromeric histone evolution in monkeyflowers

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F. R. Finseth, T. C. Nelson and L. Fishman,  PLOS Genetics,  17:e1009418. 2021-04-22 14:16:46.
Centromeres must mediate faithful chromosomal transmission during cell division and sexual reproduction, but both the DNA and protein components of centromeres diverge rapidly across species. The selfish centromere model argues that this paradoxical diversity results from a genetic conflict between centromeric DNA variants driving through female meiosis to gain over-transmission and kinetochore proteins co-evolving to re-establish Mendelian segregation. We use whole genome sequencing and genetic crossing experiments to demonstrate active evolutionary interactions between a selfish centromere and a key kinetochore protein (CenH3A) in the wildflower Mimulus guttatus. We show that both inter-specific and intra-population differences in CenH3A affect centromeric drive in hybrids, and that adaptive evolution of CenH3A has followed the recent and costly spread of the driver in a wild population. This work provides novel empirical support for the proposed antagonistic co-evolution of the DNA and protein components of centromeres, with important consequences for understanding cellular function, individual fitness, and species divergence.

Sex Determination and Dosage Compensation: femaleless Is the Link in Anopheles Mosquitoes

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M. Scott,  Current Biology,  31:R260-R263. 2021-03-08 18:03:44.
A new study finds that the femaleless gene is essential for sexual development and repression of X-chromosome dosage compensation in the malaria vector Anopheles gambiae. This could provide the basis for a new genetic approach to control this pest.

Regulating the expression of gene drives is key to increasing their invasive potential and the mitigation of resistance

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A. Hammond, X. Karlsson, I. Morianou, K. Kyrou, A. Beaghton, M. Gribble, N. Kranjc, R. Galizi, A. Burt, A. Crisanti and T. Nolan,  PLOS Genetics,  17:e1009321. 2021-01-29 21:53:25.
Here we show that restricting the cutting activity of the gene drive to the germline tissue is crucial to maintaining its potency and we illustrate how failure to restrict this activity can lead to the generation of mutations that can make mosquitoes resistant to the gene drive.

Mosquito Sexual Selection and Reproductive Control Programs

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L. J. Cator, C. A. S. Wyer and L. C. Harrington,  Trends in Parasitology,  2021-01-06 18:45:40.
Recent work has generated many key insights about specific aspects of mating behavior and physiology. Here, we synthesize these findings and classify swarming mosquito systems as polygynous. Male mating success is highly variable in swarms and evidence suggests that it is likely determined by both scramble competition between males and female choice. Incorporating this new understanding will improve both implementation and long-term stability of reproductive control tools.

A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias

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S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey,  bioRxiv,  2020.12.15.421271. 2020-12-16 14:45:08.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. Additionally, by making use of the tight linkage of white to the sex-determining locus, we were able to elucidate mechanisms of inheritance bias. We find inheritance bias through homing in double heterozygous males, but find that a previous report of the same drive occurred through meiotic drive. We propose that other previously reported 'homing'design gene drives may in fact bias their inheritance through other mechanisms with important implications for gene drive design.Competing Interest StatementThe authors have declared no competing interest.

A Gene Drive Could Wipe Out Mosquitoes. But What If We Want To Turn It Off?

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A. Winkler,  freethink,  2020-12-05 15:48:03.
Gene drives are powerful tools: they allow scientists to hack how animals pass down genes to their offspring. They could allow us to wipe out malaria-carrying mosquitoes, preserve endangered species, or fight off crop-eating pests. But once it's out in the wild, a gene drive can't be stopped from spreading — and that makes people nervous. If there are unintended consequences, we want to be able to pull the brakes. Now, UC San Diego researchers have developed a new genetic system that would let scientists halt or neutralize gene drives, even after they are released into the wild. The implications could be huge.

Targeting female flight for genetic control of mosquitoes

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D. Navarro-Payá, I. Flis, M. A. E. Anderson, P. Hawes, M. Li, O. S. Akbari, S. Basu and L. Alphey,  PLOS Neglected Tropical Diseases,  14:e0008876. 2020-12-03 20:11:01.
The yellow fever mosquito and the Southern house mosquito are important vectors of infectious diseases. Given their widespread presence across tropical and subtropical regions of the world and the increased risk of spread due to global warming there is a growing need for population control. Gene drives aim to spread a genetic element within target genes required for mosquito reproduction to disrupt their function and crash a population. Female-specific genes provide interesting candidates for population control since female mosquitoes determine the reproductive capacity of a population as well as being the actual vectors of disease. Here we describe a study on Actin-4 loss in both Aedes aegypti and Culex quinquefasciatus, where we observe female-specific disruption of flight ability and propose it as a candidate for genetic methods of population suppression.

Gene drive blocks malaria transmission in mosquitoes

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labonline,  labonline,  2020-11-09 15:46:59.
Employing a strategy known as ‘population modification’, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California (UC) researchers have made a major advance in the use of genetic technologies to control the transmission of malaria parasites. Their work has been published in the journal Nature Communications.

A gene-drive rescue system for the modification of malaria mosquito populations

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A. Adolfi,  Nature Research Bioengineering Community,  2020-11-03 18:48:29.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.

A test for meiotic drive in hybrids between Australian and Timor zebra finches

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U. Knief, W. Forstmeier, Y. Pei, J. Wolf and B. Kempenaers,  Ecology and Evolution,  2020-11-03 16:16:43.
We did not find evidence for meiotic driver loci on specific chromosomes. However, we observed a weak overall transmission bias toward Timor alleles at centromeres in females (transmission probability of Australian alleles of 47%, nominal p = 6 ? 10?5). While this is in line with the centromere drive theory, it goes against the expectation that the subspecies with the larger effective population size (i.e., the Australian zebra finch) should have evolved the more potent meiotic drivers. We thus caution against interpreting our finding as definite evidence for centromeric drive. Yet, weak centromeric meiotic drivers may be more common than generally anticipated and we encourage further studies that are designed to detect also small effect meiotic drivers.

UC researchers pioneer more effective method of blocking malaria transmission in mosquitoes

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UCI,  UCI News,  2020-11-03 14:11:01.
University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to transmitting malaria parasites by increasing gene drive effectiveness in female mosquito progeny.The second-generation gene drive system described in this paper can be applied to any of the several thousand genes that are essential for insects to survive or reproduce,” said UC San Diego Distinguished Professor Ethan Bier, a co-author of the study and science director at the Tata Institute for Genetics and Society. “While it was developed in fruit flies, this system is readily transportable to a broad selection of insect species that serve as vectors for devastating disorders such as Chagas disease, sleeping disease, leishmaniasis and arboviral diseases.”

Cellular mechanisms regulating synthetic sex ratio distortion in the Anopheles gambiae germline

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R. E. Haghighat-Khah, A. Sharma, M. R. Wunderlich, G. Morselli, L. A. Marston, C. Bamikole, A. Hall, N. Kranjc, C. Taxiarchi, I. Sharakhov and R. Galizi,  Pathogens and Global Health,  114:370-378. 2020-10-20 20:24:19.
Meiotic cleavage of rDNA repeats, located in the sex chromosomes of A. gambiae SD males, affects the competitiveness of mature sperm to fertilize the female oocyte.

Underlying beliefs linked to public opinion about gene drive and pest-specific toxin for pest control

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E. A. MacDonald, E. Edwards, J. Balanovic and F. Medvecky,  Wildlife Research,  2020-09-08 18:03:31.
Public engagement that acknowledges and responds to these underlying beliefs, rather than a traditional campaign based on biodiversity and environmental gains, may be more effective at creating a constructive dialogue about if and how these tools should be used, and to avoid replicating the polarised debate about 1080.

Gene Drive Dynamics in Natural Populations: The Importance of Density Dependence, Space, and Sex

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S. Dhole, A. L. Lloyd and F. Gould,  Annual Review of Ecology, Evolution, and Systematics,  51:505-531. 2020-08-28 21:09:09.
The spread of synthetic gene drives is often discussed in the context of panmictic populations connected by gene flow and described with simple deterministic models. Under such assumptions, an entire species could be altered by releasing a single individual carrying an invasive gene drive, such as a standard homing drive. While this remains a theoretical possibility, gene drive spread in natural populations is more complex and merits a more realistic assessment. The fate of any gene drive released in a population would be inextricably linked to the population’s ecology. Given the uncertainty often involved in ecological assessment of natural populations, understanding the sensitivity of gene drive spread to important ecological factors is critical. Here we review how different forms of density dependence, spatial heterogeneity, and mating behaviors can impact the spread of self-sustaining gene drives. We highlight specific aspects of gene drive dynamics and the target populations that need further research.

Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

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R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James,  Proceedings of the National Academy of Sciences,  202010214. 2020-08-24 12:38:12.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.

Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers

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M. A. Bravo Núñez, I. M. Sabbarini, L. E. Eide, R. L. Unckless and S. E. Zanders,  eLife,  9:e57936. 2020-08-13 13:30:44.
Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical spores, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness costs of mutations that disrupt meiotic fidelity and, in some circumstances, can even make such mutations beneficial. This work empirically demonstrates the potential for meiotic drivers to shape the evolution of gametogenesis.

Study Could Lead to Power Over Parasite

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D. Shore,  2020-08-06 14:13:11.
Scientists have long had a name for a gruesome insect that feeds on live flesh of warm-blooded mammals: C. hominivorax, Latin for “man eater.” But now, they have the parasite’s number. In a paper published this week in the journal Communications Biology, researchers from across the United States and beyond describe the assembly and analysis of the New World screwworm’s genome — a map of the fly’s 534 million DNA base pairs.

CRISPR gene drives could eliminate many vector-driven pests and diseases, but challenges remain

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J. Champer,  Genetic Literacy Project,  2020-08-06 14:11:01.
A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance.

Genomic analyses of a livestock pest, the New World screwworm, find potential targets for genetic control programs

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M. J. Scott, J. B. Benoit, R. J. Davis, S. T. Bailey, V. Varga, E. O. Martinson, P. V. Hickner, Z. Syed, G. A. Cardoso, T. T. Torres, M. T. Weirauch, E. H. Scholl, A. M. Phillippy, A. Sagel, M. Vasquez, G. Quintero and S. R. Skoda,  Nature Communications,  3:424. 2020-08-04 12:56:38.
We identify and analyze the expression of genes that are likely important for host-seeking behavior (chemosensory), development of larvae in open wounds in warm-blooded animals (heat shock protein, immune response) and for building transgenic strains for genetic control programs including gene drive (sex determination, germline). This study will underpin future experiments aimed at understanding the parasitic lifestyle of the screwworm fly and greatly facilitate future development of strains for efficient systems for genetic control of screwworm.

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

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A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, E. A. Bulger, A. Ramaiah, J. B. Bennett, G. Terradas, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James,  bioRxiv,  2020.08.02.233056. 2020-08-02 12:59:26.
We developed the first recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion.

Extensive Recombination Suppression and Epistatic Selection Causes Chromosome-Wide Differentiation of a Selfish Sex Chromosome in Drosophila pseudoobscura

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Z. L. Fuller, S. A. Koury, C. J. Leonard, R. E. Young, K. Ikegami, J. Westlake, S. Richards, S. W. Schaeffer and N. Phadnis,  Genetics,  216:205. 2020-07-30 14:22:50.
Here, we conduct a multifaceted study of the multiply inverted Drosophila pseudoobscura SR chromosome to understand the evolutionary history, genetic architecture, and present-day dynamics that shape this enigmatic selfish chromosome.

Artificial Selection Finds New Hypotheses for the Mechanism of Wolbachia-Mediated Dengue Blocking in Mosquitoes

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S. A. Ford, I. Albert, S. L. Allen, S. F. Chenoweth, M. Jones, C. Koh, A. Sebastian, L. T. Sigle and E. A. McGraw,  Frontiers in Microbiology,  11:1456. 2020-07-07 13:18:12.
We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia-mediated dengue blocking.

Recessive Z-linked lethals and the retention of haplotype diversity in a captive butterfly population

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I. J. Saccheri, S. Whiteford, C. J. Yung and A. E. van't Hof,  Heredity,  2020-05-13 18:21:56.
Sex chromosomes are predicted to harbour elevated levels of sexually antagonistic variation due to asymmetries in the heritability of recessive traits in the homogametic versus heterogametic sex.

Gene Drive – The Concept Explained

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GeneConvene Global Collaborative,  2020-03-20 12:59:44.
This short video is intended to serve as a short tutorial that explains the general idea of 'drive' or 'gene drive' in the context of genetics.  It provides the viewer with a basic understanding of the key genetic processes underlying the patterns of inheritance with which most people of familiar and explains how these processes are involved in gene drive.  This video focuses on genetics and not applications of gene drive technologies and associated issues.

Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes

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H. Schmidt, T. C. Collier, M. J. Hanemaaijer, P. D. Houston, Y. Lee and G. C. Lanzaro,  Nature Communications,  11. 2020-03-16 12:39:04.
ere we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that similar to 90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of >= 1.0%.

A 2017 horizon scan of emerging issues for global conservation and biological diversity

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Sutherland, WJB, P.; Broad, S.; Clout, M.; Connor, B.; Cote, I. M.; Dicks, L. V.; Doran, H.; Entwistle, A. C.; Fleishman, E.; Fox, M.; Gaston, K. J.; Gibbons, D. W.; Jiang, Z.; Keim, B.; Lickorish, F. A.; Markillie, P.; Monk, K. A.; Pearce-Higgins, J. W.; Peck, L. S.; Pretty, J.; Spalding, M. D.; Tonneijck, F. H.; Wintle, B. C.; Ockendon, N.,  Trends in Ecology & Evolution,  32:31-40. 2019-09-09 00:00:00.
We present the results of our eighth annual horizon scan of emerging issues likely to affect global biological diversity, the environment, and conservation efforts in the future. The potential effects of these novel issues might not yet be fully recognized or understood by the global conservation community, and the issues can be regarded as both opportunities and risks. A diverse international team with collective expertise in horizon scanning, science communication, and conservation research, practice, and policy reviewed 100 potential issues and identified 15 that qualified as emerging, with potential substantial global effects. These issues include new developments in energy storage and fuel production, sand extraction, potential solutions to combat coral bleaching and invasive marine species, and blockchain technology.

Viral gene drive in herpesviruses

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Walter, M. and E. Verdin,  bioRxiv,  2019:717017. 2019-07-30 16:38:14.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the spread of an engineered trait in populations of DNA viruses and, in particular, herpesviruses. We describe the successful transmission of a gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5) and show that gene drive viruses can efficiently target and replace wildtype populations in cell culture experiments. Our results indicate that viral gene drives can be used to suppress a viral infection and may represent a novel therapeutic strategy against herpesviruses.

Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment

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V. L. Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz,  bioRxiv,  684597. 2019-06-27 13:35:03.
CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise safety concerns for unintended gene propagation. Herein, we address this by splitting the two drive components, Cas9 and gRNAs, into separate alleles to form a novel trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes.

Transmission ratio distortion is frequent in Arabidopsis thaliana controlled crosses

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Seymour, DKC, E.; Arioz, B. I.; Koenig, D.; Weigel, D.,  Heredity,  122:294-304. 2019-01-20 00:00:00.
The equal probability of transmission of alleles from either parent during sexual reproduction is a central tenet of genetics and evolutionary biology. Yet, there are many cases where this rule is violated. The preferential transmission of alleles or genotypes is termed transmission ratio distortion (TRD). Examples of TRD have been identified in many species, implying that they are universal, but the resolution of species-wide studies of TRD are limited. We have performed a species-wide screen for TRD in over 500 segregating F-2 populations of Arabidopsis thaliana using pooled reduced-representation genome sequencing. TRD was evident in up to a quarter of surveyed populations. Most populations exhibited distortion at only one genomic region, with some regions being repeatedly affected in multiple populations. Our results begin to elucidate the species-level architecture of biased transmission of genetic material in A. thaliana, and serve as a springboard for future studies into the biological basis of TRD in this species.

Gene Drive

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Collins, CH,  Scientific American,  2018-09-14 00:00:00.
Research into a genetic engineering technology that can permanently change the traits of a population or even an entire species is progressing rapidly. The approach uses gene drives—genetic elements that pass from parents to unusually high numbers of their offspring, thereby spreading through populations rather quickly. Gene drives occur naturally but can also be engineered, and doing so could be a boon to humanity in many ways. The technology has the potential to stop insects from transmitting malaria and other terrible infections, enhance crop yields by altering pests that attack plants, render corals resistant to environmental stress, and keep invasive plants and animals from destroying ecosystems. Yet investigators are deeply aware that altering or even eliminating a species could have profound consequences. In response, they are developing rules to govern the transfer of gene drives from the laboratory into future field tests and wider use.

Gene drive to reduce malaria transmission in sub-Saharan Africa

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Burt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K.,  Journal of Responsible Innovation,  5:S66-S80. 2018-01-21 00:00:00.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of mosquitoes and/or reduce vector competence. As with any control measure, due attention should be paid to the possible evolution of resistance. No gene drive construct has yet been reported that is "field-ready" for release, and when such constructs are developed, they should be assessed on a case-by-case basis. Gene drive approaches to vector control promise to have a number of key features that motivate their continued development, and scrutiny, by all concerned.

Is it time for synthetic biodiversity conservation?

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Piaggio, AJS, G.; Seddon, P. J.; Alphey, L.; Bennett, E. L.; Carlson, R. H.; Friedman, R. M.; Kanavy, D.; Phelan, R.; Redford, K. H.; Rosales, M.; Slobodian, L.; Wheeler, K.,  Trends in Ecology & Evolution,  32:97-107. 2017-01-20 00:00:00.
Evidence indicates that, despite some critical successes, current conservation approaches are not slowing the overall rate of biodiversity loss. The field of synthetic biology, which is capable of altering natural genomes with extremely precise editing, might offer the potential to resolve some intractable conservation problems (e.g., invasive species or pathogens). However, it is our opinion that there has been insufficient engagement by the conservation community with practitioners of synthetic biology. We contend that rapid, large-scale engagement of these two communities is urgently needed to avoid unintended and deleterious ecological consequences. To this point we describe case studies where synthetic biology is currently being applied to conservation, and we highlight the benefits to conservation biologists from engaging with this emerging technology.

What’s a Gene Drive? And what are the risks and benefits?

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Risk Bites,  Arizona State University,  2015-11-30 00:00:00.
This video uses ‘white board cartooning’ as a means of illustrating concepts.

Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice

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Chmatal, LG, S. I.; Mitsainas, G. P.; Martinez-Vargas, J.; Ventura, J.; Searle, J. B.; Schultz, R. M.; Lampson, M. A.,  Current Biology,  24:2295-2300. 2014-01-15 00:00:00.
Mammalian karyotypes (number and structure of chromosomes) can vary dramatically over short evolutionary time frames [1-3]. There are examples of massive karyotype conversion, from mostly telocentric (centromere terminal) to mostly metacentric (centromere internal), in 102-10 s years [4, 5]. These changes typically reflect rapid fixation of Robertsonian (Rb) fusions, a common chromosomal rearrangement that joins two telocentric chromosomes at their centromeres to create one metacentric [5]. Fixation of Rb fusions can be explained by meiotic drive: biased chromosome segregation during female meiosis in violation of Mendel's first law [3, 6, 7]. However, there is no mechanistic explanation of why fusions would preferentially segregate to the egg in some populations, leading to fixation and karyotype change, while other populations preferentially eliminate the fusions and maintain a telocentric karyotype. Here we show, using both laboratory models and wild mice, that differences in centromere strength predict the direction of drive. Stronger centromeres, manifested by increased kinetochore protein levels and altered interactions with spindle microtubules, are preferentially retained in the egg. We find that fusions preferentially segregate to the polar body in laboratory mouse strains when the fusion centromeres are weaker than those of telocentrics. Conversely, fusion centromeres are stronger relative to telocentrics in natural house mouse populations that have changed karyotype by accumulating metacentric fusions. Our findings suggest that natural variation in centromere strength explains how the direction of drive can switch between populations. They also provide a cell biological basis of centromere drive and karyotype evolution.