Nucleosomes are DNA–protein complexes composed of histone proteins that form the basis of eukaryotic chromatin. The nucleosome was a key innovation during eukaryotic evolution, but its origin from histone homologues in Archaea remains unclear. Viral histone repeats, consisting of multiple histone paralogues within a single protein, may reflect an intermediate state. Here we examine the diversity of histones encoded by Nucleocytoviricota viruses. We identified 258 histones from 168 viral metagenomes with variable domain configurations including histone singlets, doublets, triplets and quadruplets, the latter comprising the four core histones arranged in series. Viral histone repeats branch phylogenetically between Archaea and eukaryotes and display intermediate functions in Escherichia coli, self-assembling into eukaryotic-like nucleosomes that stack into archaeal-like oligomers capable of impacting genomic activity and condensing DNA. Histone linkage also facilitates nucleosome formation, promoting eukaryotic histone assembly in E. coli. These data support the hypothesis that viral histone repeats originated in stem-eukaryotes and that nucleosome evolution proceeded through histone repeat intermediates.

核小体是由组蛋白组成的 DNA-蛋白质复合物，构成真核染色质的基础。核小体是真核进化过程中的一项关键创新，但其来自古细菌组蛋白同源物的起源仍不清楚。病毒组蛋白重复序列​​由单个蛋白质内的多个组蛋白旁系同源物组成，可能反映了中间状态。在这里，我们检查了核细胞病毒病毒编码的组蛋白的多样性。我们从 168 个病毒宏基因组中鉴定出 258 个组蛋白，这些组蛋白具有可变的结构域配置，包括组蛋白单联体、双联体、三联体和四联体，后者包含串联排列的四个核心组蛋白。病毒组蛋白在古细菌和真核生物之间重复系统发育分支，并在大肠杆菌中表现出中间功能，自组装成类似真核生物的核小体，这些核小体堆叠成能够影响基因组活性和浓缩DNA的古细菌样寡聚体。组蛋白连接还促进核小体形成，促进大肠杆菌中的真核组蛋白组装。这些数据支持病毒组蛋白重复起源于干真核生物以及核小体进化通过组蛋白重复中间体进行的假设。