The adaptive molecular landscape of reprogrammed telomeric sequences
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Melania D’Angiolo Benjamin P Barré Sakshi Khaiwal Julia Muenzner Johan Hallin Matteo De Chiara Nicolò Tellini Jonas Warringer Markus Ralser Eric Gilson Gianni LitiThis article is a preprint. Preprints have not been peer-reviewed.
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Abstract
Telomeric sequences vary across the tree of life and intimately co-evolve with telomere-binding protein complexes. However, the molecular mechanisms allowing organisms to adapt to new telomeric sequences are difficult to gauge from extant species. Here, we reprogrammed multiple yeast lines to human-like telomeric repeats to unveil their molecular and fitness response to novel telomeres. Initially, the exchange of telomere sequences resulted in genome instability, proteome remodelling and severe fitness decline. However, adaptive evolution experiments selected for repeated mutations that drove adaptation to the humanized telomeres. These consisted of the recurrent amplification of the telomere-binding protein TBF1, by complex aneuploidies, or in repeated mutations that attenuate the DNA damage response. Overall, our results outline a response that defines the adaptive molecular landscape to novel telomeric sequences.
Teaser Yeast cells adapt to novel telomeric variation through amplification of telomere-binding proteins and inactivation of a telomeric DNA damage response
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bioRxiv
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