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Centromere drive: model systems and experimental progress

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Abstract

Centromeres connect chromosomes and spindle microtubules to ensure faithful chromosome segregation. Paradoxically, despite this conserved function, centromeric DNA evolves rapidly and centromeric proteins show signatures of positive selection. The centromere drive hypothesis proposes that centromeric DNA can act like a selfish genetic element and drive non-Mendelian segregation during asymmetric female meiosis. Resulting fitness costs lead to genetic conflict with the rest of the genome and impose a selective pressure for centromeric proteins to adapt by suppressing the costs. Here, we describe experimental model systems for centromere drive in yellow monkeyflowers and mice, summarize key findings demonstrating centromere drive, and explain molecular mechanisms. We further discuss efforts to test if centromeric proteins are involved in suppressing drive-associated fitness costs, highlight a model for centromere drive and suppression in mice, and put forth outstanding questions for future research.

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Abbreviations

BUB1:

Budding uninhibited by imidazole

Cal1:

Chromosome alignment defect 1

CDC42:

Cell division cycle 42

CenH3:

Centromeric histone 3 (CENP-A orthologue in monkeyflowers)

CENP-A:

Centromere protein A

CENP-B:

Centromere protein B

CENP-C:

Centromere protein C

CENP-I:

Centromere protein I

CENP-T:

Centromere protein T

Cid:

Centromere identifier (CENP-A orthologue in Drosophila)

DSN1:

Kinetochore-associated protein DSN1 homolog

HJURP:

Holliday junction recognition protein

HP1:

Heterochromatin protein 1

HyPhy:

Hypothesis Testing using Phylogenies

INCENP:

Inner centromere protein

Kindr:

Kinesin driver

KNL1:

Kinetochore scaffold 1

MCAK:

Mitotic centromere-associated kinesin

MELT:

Met-Glu-Leu-Thr motif

MIS12:

Minichromosome instability-12

MIS18BP1:

MIS18 binding protein 1

NDC80:

Kinetochore protein NDC80 homolog

PAML:

Phylogenetic Analysis by Maximum Likelihood

RAN-GTP:

Ras-related nuclear protein-guanosine-5′-triphosphate

SGO2:

Shugoshin-2

Trkin:

TR-1 kinesin

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Funding

The research was supported by National Institutes of Health grant R35GM122475 to M.A.L. D.D. was supported by Swiss National Science Foundation Early Postdoc. Mobility grant P2GEP3_187772.

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Contributions

D.D. and M.A.L. conceived the idea for the article, performed literature search, drafted, and critically revised the manuscript.

Corresponding author

Correspondence to Michael A. Lampson.

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The authors declare no competing interests.

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Responsible Editor: Stacey Hanlon and Amanda Larracuente

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Dudka, D., Lampson, M.A. Centromere drive: model systems and experimental progress. Chromosome Res 30, 187–203 (2022). https://doi.org/10.1007/s10577-022-09696-3

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  • DOI: https://doi.org/10.1007/s10577-022-09696-3

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