Early Evolution of Histone Genes: Prevalence of an ‘Orphon’ H1 Lineage in Protostomes and Birth-and-Death Process in the H2A Family

Abstract

The study of histone evolution has experienced a rebirth, for two main reasons: the identification of new essential histone variants responsible for regulating chromatin dynamics and the subsequent contradictions posed by this variability as it pertains to their long-term evolution process. Although different evolutionary models (e.g., birth-and-death evolution, concerted evolution) may account for the observed divergence of histone genes, conclusive evidence is lacking (e.g., histone H1) or totally nonexistent (e.g., histone H2A). While most of the published work has focused on deuterostomes, very little is known about the diversification and functional differentiation mechanisms followed by histone protein subtypes in protostomes, for which histone variants have only been recently described. In this study, we identify linker and core histone genes in three clam species. Our results demonstrate the prevalence of an 'orphon' H1 lineage in molluscs, a group in which the protostome H1 and sperm nuclear basic proteins are on the verge of diversification. They share an early monophyletic origin with vertebrate-specific variants prior to the differentiation between protostomes and deuterostomes. Given the intringuing evolutionary features of the histone H1 family, we have evaluated the relative importance of gene conversion, point mutation, and selection in maintaining the diversity found among H2A subtypes in eukaryotes. We show evidence for the first time that the long-term evolution of this family is not subject to concerted evolution but, rather, to a gradual evolution following a birth-and-death model under a strong purifying selection at the protein level.

The characterization of macroH2A beyond vertebrates supports an ancestral origin and conserved role for histone variants in chromatin

“…Accordingly, molecular phylogenetic analyses support a monophyletic origin for the macroH2A lineage 36,38 as early as before the diversification of Filozoans (including Filasterea, Choanoflagellata, and Metazoa) as suggested by the presence of macroH2A in Capsaspora (Fig. 2, Fig.…”

“…12,28,31,32 For a long time macroH2A was thought to be an invention of vertebrates, culminating (together with H2A.B) the functional diversification of variants within the H2A family. [33][34][35][36] The hypothetical existence of a functional invertebrate macroH2A bears 2 critical implications: first, the evolutionary origin of this variant would have to be redefined; second, the role of macroH2A in chromatin structure and epigenetic regulation would require further examination in a broader evolutionary context. Unfortunately, no conclusive experimental information is currently available for the non-vertebrate counterpart of this histone variant.…”

Unusual Dispersion of Histone Repeats on the Whole Chromosomal Complement and Their Colocalization with Ribosomal Genes in <b><i>Rachycentron canadum</i></b> (Rachycentridae, Perciformes)

“…These include the histones (H1, H2A, H2B, H3, and H4) which exert a crucial role in the organization of chromatin [Sellos et al, 1990;Chioda et al, 2002] and may have structural (core histones: H2A, H2B, H3, and H4) and functional differences (linker histones: H1) [González-Romero et al, 2008]. Associated core histones interact with DNA, forming the nucleosome, the primary subunit of chromatin fibers [van Holde, 1988].…”

Characterization of mussel H2A.Z.2: a new H2A.Z variant preferentially expressed in germinal tissues fromMytilus

“…The mechanisms underlying the functional role of histones include the post-translational modifications of their N-terminal tails and the recruitment of specialized variants at specific chromatin regions. Among histones, the H2A family stands out due to the high number of specialized variants it displays (Gonzalez-Romero et al 2008), including some of the most studied histones so far such as H2A.X [involved in DNA repair (Li et al 2005)] and H2A.Z [essential for the survival of most eukaryotic organisms (Eirin-Lopez and Ausio 2007;Talbert and Henikoff 2010)]. Although H2A.Z is substantially divergent from its canonical H2A counterpart [60% sequence similarity in most species (Zlatanova and Thakar 2008)], this variant is highly conserved across eukaryotes, further supporting its functional relevance throughout evolution (Eirín-López et al 2009;Gonzalez-Romero et al 2008).…”

“…Among histones, the H2A family stands out due to the high number of specialized variants it displays (Gonzalez-Romero et al 2008), including some of the most studied histones so far such as H2A.X [involved in DNA repair (Li et al 2005)] and H2A.Z [essential for the survival of most eukaryotic organisms (Eirin-Lopez and Ausio 2007;Talbert and Henikoff 2010)]. Although H2A.Z is substantially divergent from its canonical H2A counterpart [60% sequence similarity in most species (Zlatanova and Thakar 2008)], this variant is highly conserved across eukaryotes, further supporting its functional relevance throughout evolution (Eirín-López et al 2009;Gonzalez-Romero et al 2008). Among its multiple roles, it is the participation of H2A.Z in the regulation of gene expression the one that has attracted more attention; in this regard, the presence of this variant at the promoters of genes is often associated with a highly dynamic chromatin state, facilitating the rapid regulation of the expression of specific genes (Dryhurst and Ausio 2014).…”