Ancient co-option of LTR retrotransposons as yeast centromeres.

Max A B Haase  ^{1   2} , Luciana Lazar-Stefanita  ³ , Lyam Baudry  ⁴ , Aleksandra Wudzinska  ³ , Xiaofan Zhou  ⁵ , Antonis Rokas  ⁶ , Chris Todd Hittinger  ⁷ , Boris Pfander  ⁸ , Andrea Musacchio  ^{9   10} , Jef D Boeke  ^{11   12   13}

• 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.