Nematode histone H2A variant evolution reveals diverse histories of retention and loss and evidence for conserved core-like variants

Abstract

Histone variants replace canonical histones in nucleosomes, sometimes changing nucleosome function. Histone variant evolution is poorly characterized, and, as we show here, reconstruction of histone protein evolution can be challenging given large differences in rates across gene lineages and across sites. The positions of introns that interrupt genes can provide complementary phylogenetic information. We combined sequence and intron data to reconstruct the evolution of three histone H2A variants in Caenorhabditis elegans to reveal disparate histories. For the variant HIS-35 (which differs from H2A by only a single glycine-to-alanine C-terminal change), we find no evidence for the hypothesis of distinct protein function: the HIS-35 alanine is ancestral and common across canonical Caenorhabditis H2A sequences, with one species encoding identical HIS-35 and canonical H2A proteins. We propose instead that HIS-35 allows for H2A expression outside of the S-phase. Genes encoding such backup functions could be functionally important yet readily replaceable; consistent with this notion, both HTAS-1 and HIS-35 exhibit phylogenetic patterns that combine long-term evolutionary persistence and recurrent loss. Finally, the H2A.Z homolog, HTZ-1, exhibits recurrent intron loss and gain, suggesting that it is intron presence, rather than a specific intron sequence or position, that may be important in histone variant expression.