Eukaryotic genomes must accomplish both compact packaging for genome stability and inheritance, as well as accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3, and H4) and by deploying histone variants with specialized chromatin functions. Some histone variants are conserved across all eukaryotes, whereas others are lineage-specific. Here, we performed detailed phylogenomic analyses of “short H2A histone” variants found in mammalian genomes. We discovered a previously undescribed typically-sized H2A variant in monotremes and marsupials, H2A.R, which may represent the common ancestor of the short H2As. We also discovered a novel class of short H2A histone variants in eutherian mammals, H2A.Q. We show that short H2A variants arose on the X Chromosome in the common ancestor of all eutherian mammals and diverged into four evolutionarily distinct clades: H2A.B, H2A.L, H2A.P, and H2A.Q. However, the repertoires of short histone H2A variants vary extensively among eutherian mammals due to lineage-specific gains and losses. Finally, we show that all four short H2As are subject to accelerated rates of protein evolution relative to both canonical and other variant H2A proteins including H2A.R. Our analyses reveal that short H2As are a unique class of testis-restricted histone variants displaying an unprecedented evolutionary dynamism. Based on their X-Chromosomal localization, genetic turnover, and testis-specific expression, we hypothesize that short H2A variants may participate in genetic conflicts involving sex chromosomes during reproduction.

真核基因组必须完成紧凑包装，以确保基因组的稳定性和遗传性以及基因表达的可及性。他们使用四种古代规范组蛋白（H2A，H2B，H3和H4）的翻译后修饰，并通过部署具有特殊染色质功能的组蛋白变体来实现此目的。一些组蛋白变体在所有真核生物中都保守，而另一些则是特定于谱系的。在这里，我们对哺乳动物基因组中的“短H2A组蛋白”变体进行了详细的系统生物学分析。我们在单音节和有袋动物H2A.R中发现了一个以前未描述的通常大小的H2A变体，它可能代表了简短的H2A的共同祖先。我们还发现了一类新型的短的H2A组蛋白变异体，在欧亚哺乳动物中，H2A.Q。我们显示短的H2A变异体出现在所有欧亚哺乳动物的共同祖先的X染色体上，并分化成四个进化上不同的进化枝：H2A.B，H2A.L，H2A.P和H2A.Q。但是，由于沿袭特异性的得失，短组蛋白H2A变异的组成在不同的以太哺乳动物之间差异很大。最后，我们显示，相对于规范的H2A和其他变异H2A蛋白（包括H2A.R），所有四个短H2A都经历了蛋白质进化的加速速率。我们的分析表明，短H2A是一类独特的受睾丸限制的组蛋白变体，显示出前所未有的进化活力。基于它们的X染色体定位，遗传更新和睾丸特异性表达，我们假设短的H2A变异可能参与生殖过程中涉及性染色体的遗传冲突。