Many eukaryotes use RNA processing, including alternative splicing, to express multiple gene products from the same gene. While the majority of mammalian genes are alternatively spliced, other eukaryotes use this process less frequently. The budding yeast Saccharomyces cerevisiae has been successfully used to study the mechanism of splicing and the splicing machinery, but alternative splicing in yeast is relatively rare and has not been extensively studied. Alternative splicing of SKI7/HBS1 is widely conserved, but yeast and a few other eukaryotes have replaced this one alternatively spliced gene with a pair of duplicated, unspliced genes as part of a whole genome doubling (WGD). Here we show that other examples of alternative splicing known to have functional consequences are widely conserved within the Saccharomycotina. We also show that a common mechanism by which alternative splicing has disappeared is by the replacement of an alternatively spliced gene with duplicate unspliced genes. This loss of alternative splicing does not always take place soon after duplication, but can take place after sufficient time has elapsed for speciation. Saccharomycetaceae that diverged before WGD use alternative splicing more frequently than S. cerevisiae. This suggests that the WGD is a major reason for the low frequency of alternative splicing in yeast. We anticipate that whole genome doublings in other lineages may have had the same effect. Having observed that two functionally distinct splice-isoforms are often replaced by duplicated genes allowed us to reverse the reasoning. We thereby identify several splice isoforms that are likely to produce two functionally distinct proteins because we find them replaced by duplicated genes in related species. We also identify some alternative splicing events that are not conserved in closely related species and thus unlikely to produce functionally distinct proteins.

中文翻译：

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使 Saccharomycotina 发芽酵母中蛋白质组多样化的选择性剪接事件的起源、保存和丢失

许多真核生物使用 RNA 加工，包括选择性剪接，来表达来自同一基因的多个基因产物。虽然大多数哺乳动物基因是交替剪接的，但其他真核生物使用这个过程的频率较低。芽殖酵母酿酒酵母已成功用于研究剪接机制和剪接机制，但酵母中的可变剪接相对较少，尚未得到广泛研究。SKI7/HBS1 的可变剪接被广泛保守，但酵母和其他一些真核生物已经用一对重复的未剪接基因替换了这个可变剪接基因，作为全基因组加倍 (WGD) 的一部分。在这里，我们展示了已知具有功能后果的替代剪接的其他例子在 Saccharomycotina 中广泛保守。我们还表明，替代剪接消失的常见机制是用重复的未剪接基因替换替代剪接基因。这种替代剪接的丢失并不总是在复制后很快发生，但可以在物种形成经过足够长的时间后发生。在 WGD 之前分化的酵母菌科比酿酒酵母更频繁地使用替代剪接。这表明 WGD 是酵母中选择性剪接频率低的主要原因。我们预计其他谱系中的全基因组加倍可能具有相同的效果。观察到两种功能不同的剪接异构体经常被重复的基因取代，这让我们能够扭转推理。因此，我们确定了几种可能产生两种功能不同的蛋白质的剪接同种型，因为我们发现它们被相关物种中的重复基因所取代。我们还确定了一些在密切相关的物种中不保守的替代剪接事件，因此不太可能产生功能不同的蛋白质。