Biased Transmission of Mouse Selfish DNA: Internal Causes of Wild-Type Embryo Mortality and Differential Gene Expression

Authors

• DMZ Silva
• T Akera

Abstract

The Homogeneously Staining Region (HSR) on mouse chromosome 1 is a selfish DNA that biases its transmission through female germline. When HSR/+ females are crossed to +/+ males, wild-type (+/+) embryos show mild mortality, leading to biased survival of HSR/+. Here, we tested whether the mortality of +/+ embryos is due to internal factors or interactions with the uterus in HSR/+ females. To distinguish between these possibilities, healthy +/+ embryos produced by crossing +/+ females with +/+ males were transferred to HSR/+ and +/+ pseudopregnant females. The survival rates of +/+ embryos were similar in both environments, suggesting that internal factors cause the +/+ embryo lethality. One possible mechanism to kill embryos by internal issues is a toxin-antidote system where toxins are deposited to all embryos but HSR/+ embryos survive because of an antidote encoded by the HSR locus. The HSR locus is a repeat DNA, encoding Sp100-rs and Sp110 genes, where SP100-rs can act as a toxin by causing DNA damage, and SP110 can serve as an antidote by suppressing DNA damage. Analyzing their expression levels showed that Sp100-rs and Sp110 were overexpressed in the Mus musculus domesticus background where bias transmission occurs, but not in the Mus musculus musculus background where biased transmission is suppressed. These results imply that HSR gene expression is essential for biased transmission. This study revealed that internal issues in +/+ embryos lead to their mortality, favoring the survival of HSR/+ embryos, with HSR gene expression possibly playing a critical role in this process.

Scientific Focus Area: Chromosome Biology

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