Data from: Purifying selection maintains dosage-sensitive genes during degeneration of the threespine stickleback Y chromosome

Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection.

性染色体（sex chromosomes）受独特的进化动力驱使，会发生重组抑制（recombination suppression）现象，进而引发序列退化并形成异形染色体对（heteromorphic chromosome pairs，即XY或ZW型）。尽管学界在脊椎动物性染色体的进化过程表征研究中已取得一定进展，但重组抑制与序列分化的典型发生机制，以及异型配子性别（heterogametic sex）中基因剂量失衡（gene dosage imbalances）的修复路径仍未明确。三刺棘鱼（threespine stickleback fish，Gasterosteus aculeatus）是探究脊椎动物性染色体进化的理想模型物种，因其拥有处于分化早期阶段的XY性染色体对。本研究结合全基因组测序（whole-genome sequencing）与转录组测序（transcriptome sequencing）技术，对性染色体上的序列进化与基因表达特征进行了系统表征。研究发现了两处独立的进化层（evolutionary strata），与Y染色体上已知的结构重排（structural rearrangements）事件一一对应。在最古老的进化层中，仅存少量功能基因，且这些基因受到强烈的纯化选择（purifying selection）作用。通过将性连锁基因（sex-linked gene）的表达模式与外类群（outgroup）中常染色体同源基因（autosomal orthologs）的表达水平进行对比，研究证实三刺棘鱼并未通过雄性个体X染色体的上调表达进化出剂量补偿（dosage compensation）机制。与之相反，在最古老的进化层中，仍保留Y染色体等位基因（Y chromosome allele）的基因，在哺乳动物与酵母中被预测为剂量敏感型（dosage sensitive）基因的占比显著富集。本研究结果表明，对于单倍体不足型基因（haploinsufficient genes），物种可通过强烈的纯化选择维持Y染色体等位基因的功能，从而规避剂量失衡问题。