Department of Biology, McMaster University, Hamilton, ON, Canada.
Mol Biol Evol. 2022 May 3;39(5). doi: 10.1093/molbev/msac087.
Low Complexity Regions (LCRs) are present in a surprisingly large number of eukaryotic proteins. These highly repetitive and compositionally biased sequences are often structurally disordered, bind promiscuously, and evolve rapidly. Frequently studied in terms of evolutionary dynamics, little is known about how LCRs affect the expression of the proteins which contain them. It would be expected that rapidly evolving LCRs are unlikely to be tolerated in strongly conserved, highly abundant proteins, leading to lower overall abundance in proteins which contain LCRs. To test this hypothesis and examine the associations of protein abundance and transcript abundance with the presence of LCRs, we have integrated high-throughput data from across mammals. We have found that LCRs are indeed associated with reduced protein abundance, but are also associated with elevated transcript abundance. These associations are qualitatively consistent across 12 human tissues and nine mammalian species. The differential impacts of LCRs on abundance at the protein and transcript level are not explained by differences in either protein degradation rates or the inefficiency of translation for LCR containing proteins. We suggest that rapidly evolving LCRs are a source of selective pressure on the regulatory mechanisms which maintain steady-state protein abundance levels.
低复杂度区域（LCRs）存在于大量真核蛋白中。这些高度重复且组成偏向的序列通常结构无序，结合具有混杂性，并且进化迅速。LCRs 经常从进化动态的角度进行研究，但对于它们如何影响包含它们的蛋白质的表达知之甚少。可以预期，在强烈保守、高度丰富的蛋白质中，快速进化的 LCRs 不太可能被容忍，这导致包含 LCRs 的蛋白质的总体丰度降低。为了验证这一假设并研究 LCR 与蛋白质丰度和转录本丰度的相关性，我们整合了来自哺乳动物的高通量数据。我们发现，LCRs 确实与蛋白质丰度降低有关，但也与转录本丰度升高有关。这些相关性在 12 个人类组织和 9 个哺乳动物物种中具有定性一致性。LCRs 对蛋白质和转录本丰度的差异影响不能用蛋白质降解率或含有 LCRs 的蛋白质翻译效率的差异来解释。我们认为，快速进化的 LCRs 是对维持稳态蛋白质丰度水平的调节机制的选择压力的来源。
