Ancient co-option of LTR retrotransposons as yeast centromeres

Nature

by Max A. B. Haase

February 19, 2026

Centromeres ensure accurate chromosome segregation, yet their DNA evolves rapidly across eukaryotes leaving the origins of new centromere architectures unclear1–4. 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’ centromeres1,5. 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. Evolutionarily related ‘proto-point’ centromeres providing resolution to the evolutionary origins of point centromeres are identified in yeast, and comparison shows they evolved in an ancestor with retrotransposon-rich centromeres and that long-terminal-repeat retrotransposons are the genetic substrate.

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Originally published on Nature on 2/19/2026