Evolution of histone H3: emergence of variants and conservation of post-translational modification sites¹This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.

Abstract

Histone H3 proteins are highly conserved across all eukaryotes and are dynamically modified by many post-translational modifications (PTMs). Here we describe a method that defines the evolution of the family of histone H3 proteins, including the emergence of functionally distinct variants. It combines information from histone H3 protein sequences in eukaryotic species with the evolution of these species as described by the tree of life (TOL) project. This so-called TOL analysis identified the time when the few observed protein sequence changes occurred and when distinct, co-existing H3 protein variants arose. Four distinct ancient duplication events were identified where replication-coupled (RC) H3 variants diverged from replication-independent (RI) forms, like histone H3.3 in animals. These independent events occurred in ancestral lineages leading to the clades of metazoa, viridiplantae, basidiomycota, and alveolata. The proto-H3 sequence in the last eukaryotic common ancestor (LECA) was expanded to at least 133 of its 135 residues. Extreme conservation of known acetylation and methylation sites of lysines and arginines predicts that these PTMs will exist across the eukaryotic crown phyla and in protists with canonical chromatin structures. Less complete conservation was found for most serine and threonine phosphorylation sites. This study demonstrates that TOL analysis can determine the evolution of slowly evolving proteins in sequence-saturated datasets.

Arabidopsisreplacement histone variant H3.3 occupies promoters of regulated genes

“…Animal and plant H3 variants evolved independently [15,57], but H3.3 incorporation patterns in plants and animals and replication-independent H3 deposition in yeast [51] have many similarities. Replication-independent chromatin assembly is essential for life, but separate H3.1 and H3.3 variants appeared independently in animals and plants.…”

“…Replication-independent chromatin assembly is essential for life, but separate H3.1 and H3.3 variants appeared independently in animals and plants. The evolutionary history of histone genes is still a matter of debate [15], but it is likely that the ability to affect higher-order chromatin structure by incorporation of specific histone variants confers major selective advantages that facilitated the repeated diversification of histones. The similarity of Arabidopsis and animal H3.3 incorporation patterns is consistent with a general association of H3.3 with several eukaryotic chromatin remodeling processes.…”

“…Replication-coupled and replication-independent (replacement) H3 histone variants evolved independently in animals, plants, basidiomycetes, and alveolates [15]. Similar to the replacement H3 variant H3.3 in animals, Arabidopsis H3.3 differs from H3.1 at positions 31, 87 and 90 but also at some additional positions [16].…”

Genome-Wide Identification, Evolutionary, and Expression Analyses of Histone H3 Variants in Plants

“…In plants, H3.1 and H3.3 are distinguished at positions 31, 87, and 90 and involve a different set of amino acids, implying that H3 variants evolved independently in plants and animals [5, 9], In addition, position 41 is a plant-specific substitution that discriminates H3.3 from H3.1 variants [6, 9]. Phylogenetic analyses also showed that H3.1 and H3.3 variants evolved independently, suggesting that H3 variants in plants and animals are analogous and result from convergent evolution [10]. …”

H3.3 demarcates GC-rich coding and subtelomeric regions and serves as potential memory mark for virulence gene expression in Plasmodium falciparum

“…In Eukarya, the histone family has expanded into canonical histones, the linker histone H1 and a great variety of histone variants for H2A, H2B and H36. Strikingly, the amino acid sequences of the four eukaryotic canonical histones and of many histone variants are extremely similar among distantly related species, although histone variants have emerged by convergent evolution789. The requirement of convergent evolution of histone variants indicates a universal theme in chromatin regulation; and indeed some histone variants display universal functions.…”