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A genetic system for biasing the sex ratio in mice.

ABSTRACT: Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a genetic system in mammals by crossing two genetically engineered mouse lines. The maternal line encodes a functional Cas9 protein on an autosomal chromosome, whereas the paternal line encodes guide RNAs on the Y chromosome targeting vital mouse genes. After fertilization, the presence of both the Y-encoded guide RNAs from the paternal sperm and the Cas9 protein from the maternal egg targets the vital genes in males. We show that these genes are specifically targeted in males and that this breeding consequently self-destructs solely males. Our results pave the way for a genetic system that allows biased sex production of livestock.

SUBMITTER: Yosef I

PROVIDER: S-EPMC6680165 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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A genetic system for biasing the sex ratio in mice.

Yosef Ido I Edry-Botzer Liat L Globus Rea R Shlomovitz Inbar I Munitz Ariel A Gerlic Motti M Qimron Udi U

EMBO reports 20190701 8

Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a genetic system in mammals by crossing two genetically engineered mouse lines. The maternal line encodes a functional Cas9 protein on an autosomal chromosome, whereas the paternal li ...[more]

PMID: 31267640

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Project description:Population dynamics predicts that on average parents should invest equally in male and female offspring; similarly, the physiology of mammalian sex determination is supposedly stochastic, producing equal numbers of sons and daughters. However, a high quality parent can maximize fitness by biasing their birth sex ratio (SR) to the sex with the greatest potential to disproportionately outperform peers. All SR manipulation theories share a fundamental prediction: grandparents who bias birth SR should produce more grandoffspring via the favored sex. The celebrated examples of biased birth SRs in nature consistent with SR manipulation theories provide compelling circumstantial evidence. However, this prediction has never been directly tested in mammals, primarily because the complete three-generation pedigrees needed to test whether individual favored offspring produce more grandoffspring for the biasing grandparent are essentially impossible to obtain in nature. Three-generation pedigrees were constructed using 90 years of captive breeding records from 198 mammalian species. Male and female grandparents consistently biased their birth SR toward the sex that maximized second-generation success. The most strongly male-biased granddams and grandsires produced respectively 29% and 25% more grandoffspring than non-skewing conspecifics. The sons of the most male-biasing granddams were 2.7 times as fecund as those of granddams with a 50∶50 bias (similar results are seen in grandsires). Daughters of the strongest female-biasing granddams were 1.2 times as fecund as those of non-biasing females (this effect is not seen in grandsires). To our knowledge, these results are the first formal test of the hypothesis that birth SR manipulation is adaptive in mammals in terms of grandchildren produced, showing that SR manipulation can explain biased birth SR in general across mammalian species. These findings also have practical implications: parental control of birth SR has the potential to accelerate genetic loss and risk of extinction within captive populations of endangered species.

Dataset Information

A genetic system for biasing the sex ratio in mice.

Publications

A genetic system for biasing the sex ratio in mice.

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