PT  - JOURNAL ARTICLE
AU  - Swadha Singh
AU  - Diana Chu
AU  - Scott Roy
TI  - Nematode histone H2A variant evolution reveals diverse histories of retention and loss, and evidence for conserved core-like variants
AID  - 10.1101/2022.03.02.482035
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.02.482035
4099  - http://biorxiv.org/content/early/2022/03/09/2022.03.02.482035.short
4100  - http://biorxiv.org/content/early/2022/03/09/2022.03.02.482035.full
AB  - 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.SIGNIFICANCE Histone variants are proteins that replace the core canonical histones in the nucleosomes and often confer specific structural and functional features. Histone variants represent a unique opportunity to study the functional significance of gene duplicates. The origin of new variants by core histone gene duplication is generally a highly asymmetrical affair marked by variant-specific changes in gene processing signals and accelerated evolution. The functions and evolutionary significance of the diverse variants found in available eukaryotic genomes remain almost entirely obscure, with only a few characterized case studies. By using a novel method that leverages intron position conservation, we reconstructed the evolutionary history of H2A variants within C. elegans and relatives. Our findings provide several insights that run counter to current paradigms of histone variant function and evolution.Competing Interest StatementThe authors have declared no competing interest.