Letter | Published:

Engineered non-Mendelian inheritance of entire parental genomes in C. elegans

Nature Biotechnology volume 34, pages 982986 (2016) | Download Citation

Abstract

The ability to rewrite the rules of genetic segregation would open new possibilities in diverse areas of biotechnology ranging from breeding to epigenetics. Here we engineer non-Mendelian inheritance of the entire maternal or paternal genome in Caenorhabditis elegans by changing the structure of the mitotic spindle during the first cell division of the zygote. Using germline-specific overexpression of a single protein, the conserved microtubule force regulator GPR-1, we increase forces that pull on spindle poles to convert the single bipolar mitotic spindle to two monopolar spindles. This generates two-cell embryos in which one cell contains only the maternal chromosomes and the other cell contains only the paternal chromosomes. As the embryo develops, each cell of the animal, including the germ cells, contains the genetic material of only one parent, resulting in hybrid F1 animals. Progeny of these animals (F2) inherit either only F0 maternal or only F0 paternal chromosomes, and thus descend from only either of their grandparents' gametes.

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Acknowledgements

The Max Planck Society funded this work.

Author information

Affiliations

  1. Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

    • Judith Besseling
    •  & Henrik Bringmann

Authors

  1. Search for Judith Besseling in:

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Contributions

J.B. performed experiments, analyzed data, and edited the manuscript. H.B. conceived the study, performed experiments, analyzed data, and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Henrik Bringmann.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–13

Videos

  1. 1.

    Supplementary Video 1

    The first cell division in the wild-type C. elegans embryo filmed by DIC and fluorescence microscopy. Histones are labeled with mCherry (red) to visualize DNA segregation. Frames were taken every 20 seconds and the display rate is 3 frames per second. A normal bipolar spindle is formed.

  2. 2.

    Supplementary Video 2

    The first cell division in C. elegans embryos that are overexpressing GPR-1 filmed by DIC and fluorescence microscopy. Histones are labeled with mCherry (red) to visualize DNA segregation. Frames were taken every 20 seconds and the display rate is 3 frames per second. Increased forces pull apart the two pronuclei. As a result, two monopolar spindles are formed that unequally segregate maternal and paternal DNA.

  3. 3.

    Supplementary Video 3

    The first cell division in C. elegans embryos that are overexpressing GPR-1 filmed by DIC and fluorescence microscopy. Histones are labeled with mCherry (red) to visualize DNA segregation. Frames were taken every 20 seconds and the display rate is 3 frames per second. A bipolar spindle is formed.

  4. 4.

    Supplementary Video 4

    An example of segregation of the paternal chromosomes to the P lineage. Anterior is to the left. The paternal pronucleus can be formally identified because it is located further to the posterior and has the two centrosomes attached. The maternal pronucleus is located initially in the anterior, has no centrosomes attached and is more mobile. Thus, the two pronuclei meet in the posterior to form the PCC. The PCC is then pulled apart so that the maternal pronucleus forms a monopolar spindle in the anterior, and the paternal pronucleus forms a monopolar spindle in the posterior. Frames were taken every 20 seconds and the display rate is 3 frames per second.

  5. 5.

    Supplementary Video 5

    A rare example of segregation of the maternal chromosomes to the P lineage. Anterior is to the left. The paternal pronucleus can be formally identified because it is located further to the posterior and has the two centrosomes attached. The maternal pronucleus is located initially in the anterior, has no centrosomes attached and is more mobile. Thus, the two pronuclei meet in the posterior to form the PCC. Note that the maternal pronucleus initially is in the anterior portion of the PCC. Then, the PCC rotates just before it is pulled apart. As a consequence, the maternal pronucleus forms a monopolar spindle in the posterior, and the paternal pronucleus forms a monopolar spindle in the anterior. Frames were taken every 20 seconds and the display rate is 3 frames per second.

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DOI

https://doi.org/10.1038/nbt.3643

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