Nematode histone H2A variant evolution reveals diverse histories of retention and loss, and evidence for conserved core-like variants
Nematode histone H2A variant evolution reveals diverse histories of retention and loss, and evidence for conserved core-like variants
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DOI：
10.1101/2022.03.02.482035
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发表时间：
2022-06
期刊：
影响因子：
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通讯作者：
Swadha Singh;Diana S Chu;S. Roy
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文献类型：
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作者：
Swadha Singh;Diana S Chu;S. Roy
组蛋白变体是替代核小体中的典型组蛋白的旁系同源物，通常赋予新的功能。尽管它们很重要，但人们对组蛋白变体如何产生和进化知之甚少。由于氨基酸高度保守性和基因谱系和位点间进化速率的巨大差异，组蛋白进化的重建具有挑战性。在这里，我们结合了108个线虫基因组的氨基酸序列和内含子位置数据，以追踪在秀丽隐杆线虫中发现的三种H2 A变体的进化历史：古老的H2A.ZHTZ-1，精子特异性的HTAS-1和HIS-35，其与典型的H2 A的不同之处在于一个单一的甘氨酸到丙氨酸的C-末端变化。我们发现了完全不同的进化历史。虽然H2A.ZHTZ-1蛋白是高度保守的，但其基因表现出重复的内含子增加和丢失。这种模式表明，内含子的存在，而不是特定的内含子序列或位置，可能是重要的H2A.Z功能。相比之下，对于HTAS-1和HIS-35，我们发现了跨物种保守的变体特异性内含子位置。HIS-35出现在小杆线虫及其姐妹群的祖先中，包括双孢属，而精子特异性变体HTAS-1最近出现在小杆线虫物种子集的祖先中。HIS-35和HTAS-1在一些后代谱系中表现出基因保留，但在其他谱系中也表现出复发性基因丢失，这表明组蛋白变体的使用或功能是高度灵活的。我们还发现，区分HIS-35与核心H2 A的单个氨基酸是祖先的，并且在典型的小杆线虫H2 A序列中是常见的，甚至鉴定出一种线虫物种具有相同的HIS-35和典型的H2 A蛋白，这一发现不是从HIS-35在蛋白质水平编码不同功能的假设中预测的。相反，我们推测HIS-35允许H2 A在S期外表达;编码这种部分冗余功能的基因可能在功能上很重要，但在进化过程中相对可替换，这与两种基因的保留和丢失的拼凑模式一致。我们的研究显示了具有不同功能的组蛋白H2 A变体的进化轨迹和内含子位置用于重建基因家族的进化历史的实用性，特别是那些经历特异质序列进化的基因家族。
Histone variants are paralogs that replace canonical histones in nucleosomes, often imparting novel functions. Despite their importance, how histone variants arise and evolve is poorly understood. Reconstruction of histone protein evolution is challenging due to high amino acid conservation and large differences in evolutionary rates across gene lineages and sites. Here we combined amino acid sequences and intron position data from 108 nematode genomes to trace the evolutionary histories of the three H2A variants found in Caenohabditis elegans: the ancient H2A.ZHTZ-1, the sperm-specific HTAS-1, and HIS-35, which differs from canonical H2A by a single glycine-to-alanine C-terminal change. We find disparate evolutionary histories. Although the H2A.ZHTZ-1 protein is highly conserved, its gene exhibits recurrent intron gain and loss. This pattern suggests that it is intron presence, rather than specific intron sequences or positions, that may be important to H2A.Z functionality. In contrast, for HTAS-1 and HIS-35, we find variant-specific intron positions that are conserved across species. HIS-35 arose in the ancestor of Caenorhabditis and its sister group, including the genus Diploscapter, while the sperm-specific variant HTAS-1 arose more recently in the ancestor of a subset of Caenorhabditis species. Both HIS-35 and HTAS-1 exhibit gene retention in some descendent lineages but also recurrent gene loss in others, suggesting that histone variant use or functionality is highly flexible. We also find that the single amino acid differentiating HIS-35 from core H2A is ancestral and common across canonical Caenorhabditis H2A sequences and even identify one nematode species that bear identical HIS-35 and canonical H2A proteins, findings that are not predicted from the hypothesis that HIS-35 encodes distinct functions at the protein level. Instead, we speculate that HIS-35 allows for H2A expression outside of the S-phase; genes encoding such partially-redundant functions may be functionally important yet relatively replaceable over evolutionary times, consistent with the patchwork pattern of retention and loss of both genes. Our study shows the evolutionary trajectory for histone H2A variants with distinct functions and the utility of intron positions for reconstructing the evolutionary history of gene families, particularly those undergoing idiosyncratic sequence evolution.