Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates.
Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates.
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DOI：
10.7554/elife.78695
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发表时间：
2023-06-12
期刊：
影响因子：
7.7
通讯作者：
Barna M
中科院分区：
文献类型：
--
作者：
Xu AF;Molinuevo R;Fazzari E;Tom H;Zhang Z;Menendez J;Casey KM;Ruggero D;Hinck L;Pritchard JK;Barna M
通过基因复制形成旁系同源物是一个核心的进化过程。对于编码蛋白质复合物（如核糖体）组分的旁系同源物，一个中心问题是它们是否编码功能不同的蛋白质，或者它们是否存在以维持等价蛋白质的适当总表达。在这里，我们使用核糖体蛋白旁系同源物Rps 27（eS 27）和Rps 27 l（eS 27 L）作为案例研究，系统地测试了进化模型的paradox功能。进化分析表明，Rps 27和Rps 27 l可能出现在同一脊椎动物祖先的全基因组复制过程中。我们发现Rps 27和Rps 27 l在小鼠细胞类型中具有负相关的mRNA丰度，其中淋巴细胞中的Rps 27最高，乳腺肺泡细胞和肝细胞中的Rps 27 l最高。通过内源性标记的Rps 27和Rps 27 l蛋白，我们证明，Rps 27-和Rps 27 l-核糖体关联优先与不同的成绩单。此外，鼠Rps 27和Rps 27 l功能丧失等位基因在不同发育阶段是纯合致死的。然而，引人注目的是，从内源性Rps 27 l基因座表达Rps 27蛋白或反之亦然完全挽救了功能丧失致死性，并产生了没有可检测的缺陷的小鼠。总之，这些发现表明Rps 27和Rps 27 l在进化上被保留，因为它们的亚功能化表达模式使得这两种基因对于实现跨细胞类型的两种等效蛋白质的必要总表达是必需的。我们的工作代表了迄今为止最深入的哺乳动物核糖体蛋白paralogs的表征，并强调了在研究paralogs时考虑蛋白质功能和表达的重要性。
The formation of paralogs through gene duplication is a core evolutionary process. For paralogs that encode components of protein complexes such as the ribosome, a central question is whether they encode functionally distinct proteins or whether they exist to maintain appropriate total expression of equivalent proteins. Here, we systematically tested evolutionary models of paralog function using the ribosomal protein paralogs Rps27 (eS27) and Rps27l (eS27L) as a case study. Evolutionary analysis suggests that Rps27 and Rps27l likely arose during whole-genome duplication(s) in a common vertebrate ancestor. We show that Rps27 and Rps27l have inversely correlated mRNA abundance across mouse cell types, with the highest Rps27 in lymphocytes and the highest Rps27l in mammary alveolar cells and hepatocytes. By endogenously tagging the Rps27 and Rps27l proteins, we demonstrate that Rps27- and Rps27l-ribosomes associate preferentially with different transcripts. Furthermore, murine Rps27 and Rps27l loss-of-function alleles are homozygous lethal at different developmental stages. However, strikingly, expressing Rps27 protein from the endogenous Rps27l locus or vice versa completely rescues loss-of-function lethality and yields mice with no detectable deficits. Together, these findings suggest that Rps27 and Rps27l are evolutionarily retained because their subfunctionalized expression patterns render both genes necessary to achieve the requisite total expression of two equivalent proteins across cell types. Our work represents the most in-depth characterization of a mammalian ribosomal protein paralog to date and highlights the importance of considering both protein function and expression when investigating paralogs.