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Targeting Sex Determination to Suppress Mosquito Populations.

ABSTRACT: Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti . Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.

SUBMITTER: Akbari O

PROVIDER: S-EPMC10168471 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Targeting Sex Determination to Suppress Mosquito Populations.

Akbari Omar O Li Ming M Kandul Nikolay N Sun Ruichen R Yang Ting T Dalla Benetta Elena E Brogan Daniel D Antoshechkin Igor I Sánchez C Héctor H Zhan Yin Peng YP DeBeaubien Nicolas N Loh YuMin Y Su Matthew M Montell Craig C Marshall John J

Research square 20230424

Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito <i>Aedes aegypti</i>. Traditional control measures have proven insuficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for <i>Aedes aegypti</i> that disrupts genes essential for sex determination and fertility, producing pr ...[more]

PMID: 37162925

Similar Datasets

Targeting Sex Determination to Suppress Mosquito Populations.

Project description:Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to effectively control wild populations of disease vectors.

| S-EPMC10153225 | biostudies-literature

Targeting sex determination to suppress mosquito populations.

Project description:Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next-generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Ae. aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to effectively control wild populations of disease vectors.

| S-EPMC10945564 | biostudies-literature

SEX DETERMINATION. A male-determining factor in the mosquito Aedes aegypti.

Project description:Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome-like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.

| S-EPMC5026532 | biostudies-literature

Moth sex determination

Project description:Sex determination in the flour moth, Ephestia kuehniella.

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Warmer waters masculinize wild populations of a fish with temperature-dependent sex determination.

Project description:Southern flounder (Paralichthys lethostigma) exhibit environmental sex determination (ESD), where environmental factors can influence phenotypic sex during early juvenile development but only in the presumed XX female genotype. Warm and cold temperatures masculinize fish with mid-range conditions producing at most 50% females. Due to sexually dimorphic growth, southern flounder fisheries are dependent upon larger females. Wild populations could be at risk of masculinization from ESD due to globally increasing water temperatures. We evaluated the effects of habitat and temperature on wild populations of juvenile southern flounder in North Carolina, USA. While northern habitats averaged temperatures near 23 °C and produced the greatest proportion of females, more southerly habitats exhibited warmer temperatures (>27 °C) and consistently produced male-biased sex ratios (up to 94% male). Rearing flounder in the laboratory under temperature regimes mimicking those of natural habitats recapitulated sex ratio differences observed across the wild populations, providing strong evidence that temperature is a key factor influencing sex ratios in nursery habitats. These studies provide evidence of habitat conditions interacting with ESD to affect a key demographic parameter in an economically important fishery. The temperature ranges that yield male-biased sex ratios are within the scope of predicted increases in ocean temperature under climate change.

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Effects of stable ectopic expression of the primary sex determination gene Yob in the mosquito Anopheles gambiae.

Project description:BACKGROUND:Mosquito-borne diseases, such as malaria, are controlled primarily by suppressing mosquito vector populations using insecticides. The current control programmes are seriously threatened by the emergence and rapid spread of resistance to approved insecticides. Genetic approaches proposed to complement the existing control efforts may be a more sustainable solution to mosquito control. All such approaches would rely on releases of modified male mosquitoes, because released females would contribute to biting and pathogen transmission. However, no sufficiently large-scale methods for sex separation in mosquitoes exist. RESULTS:Here we exploited the female embryo-killing property of the sex determining gene Yob from the African malaria mosquito, Anopheles gambiae, to evaluate the feasibility of creating transgenic An. gambiae sexing strains with a male-only phenotype. We generated An. gambiae lines with Yob expression, in both sexes, controlled by the vas2 promoter. Penetrance of the female-lethal phenotype was highly dependent on the location of the transgenic construct within the genome. A strong male bias was observed in one of the lines. All the females that survived to adulthood in that line possessed masculinized head appendages and terminal abdominal segments. They did not feed on blood, lacked host-seeking behavior, and thus were effectively sterile. Males, however, were not affected by Yob overexpression. CONCLUSIONS:Our study demonstrates that ectopic expression of Yob results in a recovery of viable, fertile males, and in death, or otherwise strongly deleterious effects, in females. This result shows potential for generation of transgenic sexing strains of Anopheles gambiae with a conditional male-only phenotype.

| S-EPMC6304757 | biostudies-other

The genetic contribution to sex determination and number of sex chromosomes vary among populations of common frogs (Rana temporaria).

Project description:The patterns of sex determination and sex differentiation have been shown to differ among geographic populations of common frogs. Notably, the association between phenotypic sex and linkage group 2 (LG2) has been found to be perfect in a northern Swedish population, but weak and variable among families in a southern one. By analyzing these populations with markers from other linkage groups, we bring two new insights: (1) the variance in phenotypic sex not accounted for by LG2 in the southern population could not be assigned to genetic factors on other linkage groups, suggesting an epigenetic component to sex determination; (2) a second linkage group (LG7) was found to co-segregate with sex and LG2 in the northern population. Given the very short timeframe since post-glacial colonization (in the order of 1000 generations) and its seemingly localized distribution, this neo-sex chromosome system might be the youngest one described so far. It does not result from a fusion, but more likely from a reciprocal translocation between the original Y chromosome (LG2) and an autosome (LG7), causing their co-segregation during male meiosis. By generating a strict linkage between several important genes from the sex-determination cascade (Dmrt1, Amh and Amhr2), this neo-sex chromosome possibly contributes to the 'differentiated sex race' syndrome (strictly genetic sex determination and early gonadal development) that characterizes this northern population.

| S-EPMC4901354 | biostudies-literature

Multilocus Sex Determination Revealed in Two Populations of Gynodioecious Wild Strawberry, Fragaria vesca subsp. bracteata.

Project description:Gynodioecy, the coexistence of females and hermaphrodites, occurs in 20% of angiosperm families and often enables transitions between hermaphroditism and dioecy. Clarifying mechanisms of sex determination in gynodioecious species can thus illuminate sexual system evolution. Genetic determination of gynodioecy, however, can be complex and is not fully characterized in any wild species. We used targeted sequence capture to genetically map a novel nuclear contributor to male sterility in a self-pollinated hermaphrodite of Fragaria vesca subsp. bracteata from the southern portion of its range. To understand its interaction with another identified locus and possibly additional loci, we performed crosses within and between two populations separated by 2000 km, phenotyped the progeny and sequenced candidate markers at both sex-determining loci. The newly mapped locus contains a high density of pentatricopeptide repeat genes, a class commonly involved in restoration of fertility caused by cytoplasmic male sterility. Examination of all crosses revealed three unlinked epistatically interacting loci that determine sexual phenotype and vary in frequency between populations. Fragaria vesca subsp. bracteata represents the first wild gynodioecious species with genomic evidence of both cytoplasmic and nuclear genes in sex determination. We propose a model for the interactions between these loci and new hypotheses for the evolution of sex determining chromosomes in the subdioecious and dioecious Fragaria.

| S-EPMC4683647 | biostudies-literature

Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex Determination.

Project description:Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here, we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whereas in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater differentiation of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems can be facilitated by subtle genetic differences.

| S-EPMC5905450 | biostudies-literature

Polymorphism of Sex Determination Amongst Wild Populations Suggests its Rapid Turnover Within the Nile Tilapia Species.

Project description:Sex-determining regions have been identified in the Nile tilapia on linkage groups (LG) 1, 20 and 23, depending on the domesticated strains used. Sex determining studies on wild populations of this species are scarce. Previous work on two wild populations, from Lake Volta (Ghana) and from Lake Koka (Ethiopia), found the sex-determining region on LG23. These populations have a Y-specific tandem duplication containing two copies of the Anti-Müllerian Hormone amh gene (named amhY and amhΔY). Here, we performed a whole-genome short-reads analysis using male and female pools on a third wild population from Lake Hora (Ethiopia). We found no association of sex with LG23, and no duplication of the amh gene. Furthermore, we found no evidence of sex linkage on LG1 or on any other LGs. Long read whole genome sequencing of a male from each population confirmed the absence of a duplicated region on LG23 in the Lake Hora male. In contrast, long reads established the structure of the Y haplotype in Koka and Kpandu males and the order of the genes in the duplicated region. Phylogenies constructed on the nuclear and mitochondrial genomes, showed a closer relationship between the two Ethiopian populations compared to the Ghanaian population, implying an absence of the LG23Y sex-determination region in Lake Hora males. Our study supports the hypothesis that the amh region is not the sex-determining region in Hora males. The absence of the Y amh duplication in the Lake Hora population reflects a rapid change in sex determination within Nile tilapia populations. The genetic basis of sex determination in the Lake Hora population remains unknown.

| S-EPMC9152217 | biostudies-literature

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