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bioRxiv · 10.1101/2025.06.26.661778

Histone diversity in the archaeal domain of life

Laursen, S. p.·Luger, K.
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Abstract

Archaea represent a distinct domain of life that is genetically and biochemically unique from bacteria and eukaryotes. Two-thirds of all archaea encode histones, proteins that are ubiquitously used to structure chromatin in eukaryotes. Archaeal histone sequences are much less conserved than their eukaryotic counterparts, yet insight into how they structure DNA is limited to only a few species that fail to represent the diversity of the archaeal domain. Archaea have adapted to the most diverse and extreme environments on our planet, requiring protection of the genome against a multitude of external pressures. Here, we use bioinformatics, structure prediction, and molecular dynamics simulations to survey the diversity of histone-like sequences in all available archaeal genomes and to understand how they might interact with DNA. We have identified five distinct types of histones which are combined in seven different strategies, involving either single histones, multiple histones of the same type, or combinations of several types of histones in one genome. We show that some strategies correlate with environmental pressures, and some are phylogenetically restricted. Despite highly divergent amino acid sequences, structure predictions and simulations suggest similar histone DNA binding modes for most classes. Our work provides a guide to efficiently survey diverse strategies for histone-based DNA organization in archaea using biophysical and structural approaches, for a complete view of the rich diversity of histone strategies in the archaeal domain in a targeted manner.

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Laursen, S. p., Luger, K.. 2025-06-27. Histone diversity in the archaeal domain of life. https://doi.org/10.1101/2025.06.26.661778

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