Centromere drive: model systems and experimental progress

Dudka, Damian; Lampson, Michael A.

doi:10.1007/s10577-022-09696-3

Cited by 16 publications

(18 citation statements)

References 81 publications

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“…Therefore, we propose that innovation in the CENP-O C-terminal RWD domain modulates interactions with other centromeric components (possibly CENP-Q and -U) necessary to form a stable CENP-OPQUR complex at centromeres (Foltz et al, 2006; Hori et al, 2008; Kagawa et al, 2014; Minoshima et al, 2005; Okada et al, 2006; Pesenti et al, 2018), potentially stabilizing kinetochore-microtubules to counteract destabilizing activities associated with driving centromeres (Akera et al, 2019; Wu et al, 2018). Future work using centromere drive models (reviewed in (Dudka and Lampson, 2022)) will be needed to experimentally test this idea. Overall, we show how FREEDA can help derive evolutionary hypotheses and guide experimental testing of functional innovation, starting from just a gene name, making it a powerful tool for incorporating evolutionary analyses into cell biology research and generating new insights into essential cellular processes.…”

Section: Discussionmentioning

confidence: 99%

“…These analyses provide a starting point for future experiments probing the functional impacts of innovation, including testing whether positive selection reduces fitness costs associated with centromere drive (reviewed in (Dudka and Lampson, 2022)).…”

Section: Discussionmentioning

confidence: 99%

“…FREEDA provides the key functionalities listed above, including a unique ability to map residues under positive selection onto any predicted protein structure. As a proof-of-principle, we first use FREEDA to map positive selection across centromeric proteins in rodents, as mice are currently the only experimentally tractable cell biological model system for centromere drive (reviewed in (Dudka and Lampson, 2022)). Guided by these computational analyses, we use the evolutionary mismatch approach to provide experimental evidence of functional innovation in the centromeric protein CENP-O.…”

Section: Introductionmentioning

confidence: 99%

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FREEDA: an automated computational pipeline guides experimental testing of protein innovation by detecting positive selection

Dudka

Akins

Lampson

2023

Preprint

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Cell biologists typically focus on conserved regions of a protein, overlooking innovations that can shape its function over evolutionary time. Computational analyses can reveal potential innovations by detecting statistical signatures of positive selection that leads to rapid accumulation of beneficial mutations. However, these approaches are not easily accessible to non-specialists, limiting their use in cell biology. Here, we present an automated computational pipeline FREEDA (Finder of Rapidly Evolving Exons in De novo Assemblies) that provides a simple graphical user interface requiring only a gene name, integrates widely used molecular evolution tools to detect positive selection, and maps results onto protein structures predicted by AlphaFold. Applying FREEDA to >100 mouse centromere proteins, we find evidence of positive selection in intrinsically disordered regions of ancient domains, suggesting innovation of essential functions. As a proof-of-principle experiment, we show innovation in centromere binding of CENP-O. Overall, we provide an accessible computational tool to guide cell biology research and apply it to experimentally demonstrate functional innovation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FREEDA: an automated computational pipeline guides experimental testing of protein innovation by detecting positive selection

Dudka

Akins

Lampson

2023

Preprint

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“…The hypothesis that heterozygous females would transfer more Rb chromosomes to their offspring than males arises from findings in different organisms (de Villena and Sapienza, 2001;Fishman and Saunders, 2008;Presgraves, 2009;Dudka and Lampson, 2022). In addition, segregational asymmetry is difficult to explain in males, whereas in female meiosis, such asymmetry is possible because the chromosomes that eventually remain in the oocyte can be inherited, while those that remain in the polocytes are necessarily lost (Lindholm et al, 2016).…”

Section: Animalmentioning

confidence: 99%

Quantitative analysis of Robertsonian chromosomes inherited by descendants from multiple Rb heterozygotes of Mus m. Domesticus

Ayarza

Cavada²,

Arévalo³

et al. 2022

Front. Cell Dev. Biol.

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Robertsonian translocation is the most common chromosomal rearrangement in mammals, and represents the type of chromosomal change that most effectively contributes to speciation in natural populations. Rb translocations involve double-strand DNA breaks at the centromere level in two telocentric chromosomes, followed by repair ligation of the respective long arms, creating a metacentric Rb chromosome. Many different chromosomal races have been described in Mus musculus domesticus that show reduced chromosome numbers due to the presence of Rb metacentric chromosomes. The crossroads between ancestral telocentrics and the new metacentric chromosomes should be resolved in the meiotic cells of the heterozygote individuals, which form trivalents. The preferential segregation of metacentric chromosomes to the egg during female meiosis I has been proposed to favor their fixation and eventual conversion of a telocentric karyotype to a metacentric karyotype. This biased segregation, a form of meiotic drive, explains the karyotype changes in mammalian species that have accumulated Rb fusions. We studied and compared the number of Rb chromosomes inherited by the offspring of multiple Rb heterozygous of M. domesticus in reciprocal crosses. We did not find that the Rb chromosomes were inherited preferentially with respect to the telocentric chromosomes; therefore, we found no evidence for the meiotic drive, nor was there a random distribution of Rb chromosomes inherited by the descendants.

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“…One powerful model system for assessing the molecular basis for female meiotic drive is the mouse ( 15 ). Prior work has demonstrated that major differences in the abundance of repetitive centromere DNA between inbred laboratory strains or species lead to differences in which chromosomes are more likely to be inherited through meiosis ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Centromere innovations within a mouse species

Gambogi,

Pandey,

Dawicki-McKenna

et al. 2023

Sci. Adv.

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Mammalian centromeres direct faithful genetic inheritance and are typically characterized by regions of highly repetitive and rapidly evolving DNA. We focused on a mouse species, Mus pahari, that we found has evolved to house centromere-specifying centromere protein-A (CENP-A) nucleosomes at the nexus of a satellite repeat that we identified and termed π-satellite (π-sat), a small number of recruitment sites for CENP-B, and short stretches of perfect telomere repeats. One M. pahari chromosome, however, houses a radically divergent centromere harboring ~6 mega–base pairs of a homogenized π-sat–related repeat, π-sat B , that contains >20,000 functional CENP-B boxes. There, CENP-B abundance promotes accumulation of microtubule-binding components of the kinetochore and a microtubule-destabilizing kinesin of the inner centromere. We propose that the balance of pro- and anti-microtubule binding by the new centromere is what permits it to segregate during cell division with high fidelity alongside the older ones whose sequence creates a markedly different molecular composition.

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Centromere drive: model systems and experimental progress

Cited by 16 publications

References 81 publications

FREEDA: an automated computational pipeline guides experimental testing of protein innovation by detecting positive selection

FREEDA: an automated computational pipeline guides experimental testing of protein innovation by detecting positive selection

Quantitative analysis of Robertsonian chromosomes inherited by descendants from multiple Rb heterozygotes of Mus m. Domesticus

Centromere innovations within a mouse species

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