Alternative splicing and subfunctionalization generates functional diversity in fungal proteomes.

Alternative splicing and subfunctionalization generates functional diversity in fungal proteomes.
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DOI:
10.1371/journal.pgen.1003376
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发表时间:
2013
期刊:
影响因子:
4.5
通讯作者:
van Hoof A
van Hoof A
中科院分区:
生物学2区
文献类型:
--
作者:
Marshall AN;Montealegre MC;Jiménez-López C;Lorenz MC;van Hoof A

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后生动物通常使用选择性剪接从一个基因产生一种以上的蛋白质。然而,通过选择性剪接实现的蛋白质组多样化在真菌中要罕见得多。我们在这里描述了一个古老的真菌选择性剪接事件中,这两种蛋白质是从一个单一的选择性剪接的祖先SKI 7/HBS 1基因保留在许多物种中的子囊菌门和担子菌门。虽然从单个SKI 7/HBS 1基因表达两种蛋白质的能力在许多真菌中是保守的,但它们实现这一点的确切机制各不相同。选择性剪接在酿酒酵母全基因组复制事件后丢失,因为这两个基因亚功能化为目前功能不同的HBS 1和SKI 7基因。当在酵母中表达时,来自Lachancea kluyveri的单个基因产生两种功能不同的蛋白质。其中一种蛋白质的表达与hbs 1突变互补,但与ski 7突变无关,而另一种蛋白质与ski 7突变互补,但与hbs 1无关。这是第一个已知的情况下,亚功能的损失选择性剪接在酵母。巧合的是,祖先的选择性剪接基因也在粟酒裂殖酵母中复制,随后发生亚功能化和剪接丧失。真菌中选择性剪接的缺失导致的类似亚功能化也解释了芽殖酵母Tetrapisispora blattae中两个PTC 7基因的存在,表明这是保留重复选择性剪接基因的常见机制。复制基因在产生新功能中的作用是进化中的一个重要问题。几乎所有的物种都有重复的基因,执行相似但不相同的功能。当一个基因通过选择性剪接产生多个mRNA,这些mRNA被翻译成多个相似的蛋白质时,也可以产生执行不同功能的相似蛋白质。这种选择性剪接在动物细胞中很普遍,但在真菌中却很少见。在这里,我们表明,大多数真菌使用选择性剪接,使Ski 7蛋白和Hbs 1蛋白从同一个基因。两种真菌,芽殖酵母和裂殖酵母,比其他真菌更好地表征,巧合的是,它们都复制了这种选择性剪接的基因,导致两个不再选择性剪接的相似基因。最后,我们描述了另一个例子,其中两个重复基因取代一个选择性剪接基因,这表明这是重复基因之间划分功能的常见机制。
Alternative splicing is commonly used by the Metazoa to generate more than one protein from a gene. However, such diversification of the proteome by alternative splicing is much rarer in fungi. We describe here an ancient fungal alternative splicing event in which these two proteins are generated from a single alternatively spliced ancestral SKI7/HBS1 gene retained in many species in both the Ascomycota and Basidiomycota. While the ability to express two proteins from a single SKI7/HBS1 gene is conserved in many fungi, the exact mechanism by which they achieve this varies. The alternative splicing was lost in Saccharomyces cerevisiae following the whole-genome duplication event as these two genes subfunctionalized into the present functionally distinct HBS1 and SKI7 genes. When expressed in yeast, the single gene from Lachancea kluyveri generates two functionally distinct proteins. Expression of one of these proteins complements hbs1, but not ski7 mutations, while the other protein complements ski7, but not hbs1. This is the first known case of subfunctionalization by loss of alternative splicing in yeast. By coincidence, the ancestral alternatively spliced gene was also duplicated in Schizosaccharomyces pombe with subsequent subfunctionalization and loss of splicing. Similar subfunctionalization by loss of alternative splicing in fungi also explains the presence of two PTC7 genes in the budding yeast Tetrapisispora blattae, suggesting that this is a common mechanism to preserve duplicate alternatively spliced genes. The role of duplicated genes in originating new functions is an important question in evolution. Almost all species have duplicated genes that carry out similar but not identical functions. Similar proteins that perform different functions can also be generated when one gene generates multiple mRNAs by alternative splicing that are translated into multiple similar proteins. This alternative splicing is prevalent in animal cells, but much rarer in fungi. Here we show that most fungi use alternative splicing to make a Ski7 protein and a Hbs1 protein from the same gene. Two fungi, budding yeast and fission yeast, have been much better characterized than other fungi, and co-incidentally they both have duplicated this alternatively spliced gene, resulting in two similar genes that are no longer alternatively spliced. Finally, we describe another example where two duplicate genes replace one alternatively spliced gene, suggesting that this is a common mechanism to divide functions among duplicate genes.
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