Ancient co-option of LTR retrotransposons as yeast centromeres

Max A B Haase; Luciana Lazar-Stefanita; Lyam Baudry; Aleksandra Wudzinska; Xiaofan Zhou; Antonis Rokas; Chris Todd Hittinger; Boris Pfander; Andrea Musacchio; Jef D Boeke

doi:10.1038/s41586-025-10092-0

Ancient co-option of LTR retrotransposons as yeast centromeres

Nature. 2026 Feb 18. doi: 10.1038/s41586-025-10092-0. Online ahead of print.

Authors

Max A B Haase^{1

2}, Luciana Lazar-Stefanita³, Lyam Baudry⁴, Aleksandra Wudzinska³, Xiaofan Zhou⁵, Antonis Rokas⁶, Chris Todd Hittinger⁷, Boris Pfander⁸, Andrea Musacchio^{9

10}, Jef D Boeke^{11

12

13}

Affiliations

¹ Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany. max.haase@mpi-dortmund.mpg.de.
² Institute for Systems Genetics, NYU Langone Health, New York, NY, USA. max.haase@mpi-dortmund.mpg.de.
³ Institute for Systems Genetics, NYU Langone Health, New York, NY, USA.
⁴ Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
⁵ Guangdong Provincial Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Center, South China Agricultural University, Guangzhou, China.
⁶ Department of Biological Sciences and Evolutionary Studies Initiative, Vanderbilt University, Nashville, TN, USA.
⁷ Laboratory of Genetics, Center for Genomic Science Innovation, J. F. Crow Institute for the Study of Evolution, DOE Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Cell Biology, Dortmund Life Science Center (DOLCE), Department of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany.
⁹ Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
¹⁰ Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.
¹¹ Institute for Systems Genetics, NYU Langone Health, New York, NY, USA. Jef.Boeke@nyulangone.org.
¹² Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA. Jef.Boeke@nyulangone.org.
¹³ Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, NY, USA. Jef.Boeke@nyulangone.org.

PMID: 41708848
DOI: 10.1038/s41586-025-10092-0

Abstract

Centromeres ensure accurate chromosome segregation, yet their DNA evolves rapidly across eukaryotes leaving the origins of new centromere architectures unclear^1-4. The brewer's yeast Saccharomyces cerevisiae exemplifies this long-standing puzzle. Its centromeres shifted ancestrally from large, repeat-rich, epigenetically specified forms to the compact, genetically defined 'point' centromeres^1,5. How this transition occurred has remained unresolved⁶. Here we identify evolutionarily related 'proto-point' centromeres that provide a resolution to the evolutionary origins of point centromeres. Proto-point centromeres contain a single centromeric nucleosome positioned over an AT-rich core, accompanied by relaxed organization and sequence variability of flanking cis-elements. In two species, these proto-point centromeres lie within retrotransposon-derived repeat clusters, linking ancestral repeat-rich centromeres to genetically encoded ones. Comparative and phylogenetic analyses indicate that proto-point and point centromeres evolved in an ancestor with retrotransposon-rich centromeres. These results identify long-terminal-repeat retrotransposons, specifically Ty5 sequences, as the genetic substrate for point-centromere evolution and provide a mechanistic route by which an epigenetic centromere can become genetically specified. More broadly, they show how selfish elements can be co-opted to perform essential chromosomal functions.

Abstract

Grants and funding