From junk to deleterious: Natural subtelomeric repeat amplifications impact fitness and cellular phenotypes in yeast

Authors

Henault, M., Fogg, V., Heasley, L. R.

Abstract

Eukaryotic genomes exhibit astounding levels of complexity. Much of this complexity resides in repetitive DNA thought to evolve neutrally, meaning that its impact on fitness is so small that natural selection cannot act efficiently to favor or purge it. Yet, repetitive DNA greatly facilitates the generation of structural variants (SVs), which fuel evolution with both adaptive and deleterious variation. How SVs involving initially neutral repetitive DNA can bring new evolutionarily meaningful impacts is not well understood. This is in part because finding and interpreting molecular signatures of these transitions using comparative genomics over long evolutionary timescales is challenging. Here, we document one such transition over a microevolutionary timescale using budding yeast population genomics. We characterize multiple massive amplifications of the Y' element, a highly polymorphic and dispensable subtelomeric tandem repeat. We uncover extreme structural diversity in Y' tandem amplifications among near-isogenic strains, and show that these amplifications bring a significant fitness cost. We further link Y' amplifications with transcriptome rewiring, heightened DNA replication stress sensitivity and DNA damage response activation. Together, our results support a model by which massive subtelomeric tandem amplification pushed a repetitive DNA family outside of effective neutrality to become deleterious.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Jul 2026.

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