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A new preprint on bioRxiv reverses the previously held beliefs about DNA organization in bacteria and the proteins responsible for their structure. The study characterized histone proteins in two distinct bacteria species, although the arrangement of these histone proteins was vastly different than those of eukaryotes.
Histones have been extensively studied for their roles in chromosome structure and gene expression and are highly abundant in eukaryotes and archaea. Until this study, researchers hadn’t identified bacteria with histones, and it was commonly believed that they were absent from this domain of life.
An orthogonal set of proteins exist in bacteria as well as nucleoid-associated proteins that assist with DNA structure; however, previous work has shown these proteins can be removed without deleterious effects1. During past homology searches, the presence of proteins with putative histone fold domains was also identified in some bacterial genomes2, but their functions remained largely unknown.
The work began when the researchers searched through a database of bacterial genomes for proteins with histone fold domains. They identified 416 proteins with histone fold domains and two major histone size classes with structural characteristics similar to archaeal histones. These findings corroborate previous identifications and prompted the team to take a closer look at lineages with phylogenetic persistence of the proteins, such as the phylum Bdellovibrionota and the order Leptospirales.
Used as a model organism for Bdellovibrionota, Bdellovibrio bacteriovorus is a bacterial predator that opens the membranes of gram-negative bacteria and consumes its prey by digesting and using their cellular contents. B. bacteriovorus was shown to encode two predicted singlet histones (Bd0055 and Bd3044) and transcriptomic data showed high levels of expression of Bd0055.
Further investigation showed that, when isolated, Bd0055 was highly abundant and present in the nucleoid. Crystal structures of Bd0055 highlighted some similarities to eukaryotic and archaeal histones, but with reduced size in important domains necessary for its structure and function.
Additional experiments shed light on the most interesting discovery of the study — the histones in B. bacteriovorus completely coated the linear DNA by binding end-on, which formed a nucleohistone filament. This “inside-out” arrangement of histones and DNA has not been detected in any other organism and introduces a divergence in the way histones bind.
To understand the importance of histones outside of Bdellovibrionota, the researchers examined the proteins in the pathogen Leptospira interrogans. As seen previously, the histone Bd0055 was conserved, abundant, and present within nucleoid enrichments. The researchers repeatedly failed in their attempts to delete the gene encoding Bd0055 from L. interrogans, indicating that the histones are essential for its survival.
This work has demonstrated the importance and distribution of histones across all domains of life. Additional work will need to be done to identify histones in other bacteria and understand if they bind DNA similar to Bd0055.
References:
Histones have been extensively studied for their roles in chromosome structure and gene expression and are highly abundant in eukaryotes and archaea. Until this study, researchers hadn’t identified bacteria with histones, and it was commonly believed that they were absent from this domain of life.
An orthogonal set of proteins exist in bacteria as well as nucleoid-associated proteins that assist with DNA structure; however, previous work has shown these proteins can be removed without deleterious effects1. During past homology searches, the presence of proteins with putative histone fold domains was also identified in some bacterial genomes2, but their functions remained largely unknown.
The work began when the researchers searched through a database of bacterial genomes for proteins with histone fold domains. They identified 416 proteins with histone fold domains and two major histone size classes with structural characteristics similar to archaeal histones. These findings corroborate previous identifications and prompted the team to take a closer look at lineages with phylogenetic persistence of the proteins, such as the phylum Bdellovibrionota and the order Leptospirales.
Used as a model organism for Bdellovibrionota, Bdellovibrio bacteriovorus is a bacterial predator that opens the membranes of gram-negative bacteria and consumes its prey by digesting and using their cellular contents. B. bacteriovorus was shown to encode two predicted singlet histones (Bd0055 and Bd3044) and transcriptomic data showed high levels of expression of Bd0055.
Further investigation showed that, when isolated, Bd0055 was highly abundant and present in the nucleoid. Crystal structures of Bd0055 highlighted some similarities to eukaryotic and archaeal histones, but with reduced size in important domains necessary for its structure and function.
Additional experiments shed light on the most interesting discovery of the study — the histones in B. bacteriovorus completely coated the linear DNA by binding end-on, which formed a nucleohistone filament. This “inside-out” arrangement of histones and DNA has not been detected in any other organism and introduces a divergence in the way histones bind.
To understand the importance of histones outside of Bdellovibrionota, the researchers examined the proteins in the pathogen Leptospira interrogans. As seen previously, the histone Bd0055 was conserved, abundant, and present within nucleoid enrichments. The researchers repeatedly failed in their attempts to delete the gene encoding Bd0055 from L. interrogans, indicating that the histones are essential for its survival.
This work has demonstrated the importance and distribution of histones across all domains of life. Additional work will need to be done to identify histones in other bacteria and understand if they bind DNA similar to Bd0055.
References:
- Baba T., T. Ara, M. Hasegawa, Y. Takai, Y. Okumura, et al., 2006 Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2. https://doi.org/10.1038/msb4100050
- Alva V., and A. N. Lupas, 2018 Histones predate the split between bacteria and archaea. Bioinformatics 35: 2349–2353. https://doi.org/10.1093/bioinformatics/bty1000