A unified phylogeny-based nomenclature for histone variants

Abstract

Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and complicate database searches. We propose here a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable. The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function. A key feature is the consistent use of punctuation to represent phylogenetic divergence, making explicit the relationships among variant subtypes that have previously been implicit or unclear. We recommend that by default new histone variants be named with organism-specific paralog-number suffixes that lack phylogenetic implication, while letter suffixes be reserved for structurally distinct clades of variants. For clarity and searchability, we encourage the use of descriptors that are separate from the phylogeny-based variant name to indicate developmental and other properties of variants that may be independent of structure.

Figure 1

Unrooted H2A phylogeny. H2A.Z is a monophyletic clade present in all eukaryotes, while macroH2A (mH2A) is restricted to animals and H2A.B (H2A.Bbd) and H2A.L (H2AL) are confined to mammals. Paraphyletic or polyphyetic H2A.X and replication-coupled H2As have diverged repeatedly. Alignments and trees constructed using default ClustalW parameters and displayed using Dendroscope [45].

Figure 2

Unrooted H2B phylogeny. TS H2B.1 (TH2B), H2B.W (H2BFWT) and subH2B (SubH2Bv) are mammal-specific clades. Highly divergent generative cell H2Bs in plants do not form a clear clade. Apicomplexan H2Bv does not appear to be related to trypanosome H2BV, despite the fact that both are thought to interact with H2A.Z.

Figure 3

Unrooted H3 phylogeny. (A) cenH3s are not clearly separable from the divergent H3s of excavates and of plant generative cells. (B) Replication-independent H3.3s and replication-coupled H3s have diverged repeatedly in different lineages.

Figure 4

Unrooted H4 phylogeny. Most eukaryotes have a single form of H4, and most divergence in H4s is found in excavates, amoebozoans, and ciliates versus other eukaryotes.

Figure 5

Unrooted H1 phylogeny. H1.0 (H1°) is an animal-specific clade, including avian H5. H1.10 (H1x) is found in vertebrates. Mammal-specific clades include H1.7 (H1T2) and H1.9 (Hils1). H1.8 (H1oo) and H1.6 (H1t) are also monophyletic in mammals, but other TS H1s and oocyte H1s are not clearly members of the same clades.