helsenjana.bsky.social
Evolutionary cell biology, chromosomes, yeasts, and occasional SciArtπ§¬π§ͺπ¨. Postdoctoral fellow at the labs of Gautam Dey (EMBL) and Gavin Sherlock (Stanford University).
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Super nice to see this out! Congrats Hashim!
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Thank you, that's very nice to hear! π
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Thank you Max! π
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This rewarding project came to fruition with the help of my amazing colleagues @gsherloc.bsky.social, @gautamdey.bsky.social, and @kausthubh.bsky.social, and with the support of @embl.org, Stanford University, and the Life Science Alliance. (8/8)
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Our study challenges the traditional view of centromere drive as the sole driver of centromere evolution. We propose a multi-faceted model involving drift and selection during both mitosis and meiosis, shaped by constraints imposed by the kinetochore interface. (7/8)
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Centromere transitions aren't random!
Our findings suggest that the kinetochore interface dictates which centromere changes are tolerated. Coevolution between the kinetochore and centromere sequences likely drives these constrained transitions. (6/8)
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Centromere variants can also spread through populations via sexual reproduction. In budding yeasts, microhomology-mediated mutations seem to be the key driver in the emergence of these novel centromere variants. (5/8)
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Centromere transitions turn out to be a gradual, step-by-step process. Through simulations and in vivo centromere function experiments, we show that selection plays a crucial role in driving these changes! (4/8)
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We developed a new tool, PCAn π, to systematically map point centromeres across budding yeasts, revealing remarkable centromere variation! (3/8)
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Unlike genes, species with monocentric chromosomes possess multiple centromeres, one on each chromosome. This makes centromere evolution conceptually quite different from gene evolution.
Our work aimed to shed light on the fundamental evolutionary principles underlying centromere transitions. (2/8)
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Subconscious motivation, I promise, but I was indeed somewhat intrigued by those covers as a child π
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Amazing, thank you π
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I'm one of those! Can I be added?
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I'd love to be added!
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This is great! Can I be added too?
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Thank you so much, that's so nice to hear! Always happy to answer any questions that might come up π
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Just the list I was looking for, thank you! I'd love to be included too if there's still space.
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Thanks so much π
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Thanks for putting this together! I'd also love to be included π
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Curious what changes we made since our preprint from October β23? Check out the peer reviewer reports. Also, you can check out this complementary study from 2 weeks ago in @CurrentBiology examining the spindle defects of 2-chromosome strains doi.org/10.1016/j.cub.2024.06.058 9/9
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This rewarding project came to fruition with the help of my amazing colleagues @gsherloc.bsky.social , @gautamdey.bsky.social, Hashim Reza and Ricardo Carvalho, and with the support of EMBL, Stanford University, and the Life Science Alliance. 8/9
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To summarise: the budding yeast spindle robustly supports karyotypes with at least 5 chromosomes, showcasing how core cellular features can set limitations for evolution. 7/9
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Why do cells need at least 5 centromeres? Our study reveals that 4 kinetochore microtubules cannot generate sufficient inward force to counteract the outward forces in the metaphase spindle, causing kinetochores to decluster and triggering the spindle assembly checkpoint. 6/9
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How does diploidization get rid of a mitotic delay? Diploidization effectively doubles the number of chromosomes above the critical limit. Turns out having 5 centromeres is sufficient to completely overcome the delay. 5/9
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What exactly is the cause of this delay? By evolving cells with low chromosome counts in the lab, we show that cells can completely get rid of this delay through one quick fix β¨
diploidization. 4/9
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Using a set of budding yeast strains in which the native chromosomes have been successively fused, we show that cells can tolerate large changes in karyotype. But, only up until a critical point: cells with fewer than 5 chromosomes experience a mitotic delay. 3/9
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Chromosome numbers can vary widely in nature, even between closely related species. Despite this, the mitotic machinery must accurately segregate each chromosome every cell cycle. We sought to understand the physical constraints dictating chromosome number evolution. 2/9
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Thanks Omaya π
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To summarise: the budding yeast spindle robustly supports karyotypes with at least five chromosomes, showcasing how the mechanics of a core cellular process can constrain evolutionary processes. 8/8
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This in turn causes kinetochore declustering, triggering of the spindle assembly checkpoint, and results in a delay in metaphase. 7/8
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What goes wrong in cells with fewer than five centromeres? We show that in these cells, the number of kinetochore-microtubule attachments is insufficient to counter outward forces in the metaphase spindle. 6/8
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How does diploidization repair the defect? Diploidization effectively doubles the number of chromosomes above the critical limit, and we show that having five centromeres is sufficient to overcome both the growth and mitotic defect. 5/8
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Can cells repair this defect? We evolved cells with low chromosome counts in the lab, and show that cells can indeed overcome the growth defect, and they do so by diploidization. 4/8
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Using a set of budding yeast strains in which the native chromosomes have been successively fused, we show that cells tolerate large changes in karyotype very well, but only up until a critical point. Cells with fewer than five chromosomes display both growth and mitotic defects. 3/8
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Chromosome numbers can vary widely in nature, even between closely related species. Regardless, the mitotic machinery must accurately segregate each chromosome every cell cycle. Here, we set out to explore the physical constraints dictating chromosome number evolution. 2/8