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转录本丰度的进化受蛋白质低复杂度区域插入缺失的影响。

Evolution of Transcript Abundance is Influenced by Indels in Protein Low Complexity Regions.

机构信息

Department of Biology, McMaster University, Hamilton, ON, Canada.

出版信息

J Mol Evol. 2024 Apr;92(2):153-168. doi: 10.1007/s00239-024-10158-z. Epub 2024 Mar 14.

Abstract

Protein Protein low complexity regions (LCRs) are compositionally biased amino acid sequences, many of which have significant evolutionary impacts on the proteins which contain them. They are mutationally unstable experiencing higher rates of indels and substitutions than higher complexity regions. LCRs also impact the expression of their proteins, likely through multiple effects along the path from gene transcription, through translation, and eventual protein degradation. It has been observed that proteins which contain LCRs are associated with elevated transcript abundance (TAb), despite having lower protein abundance. We have gathered and integrated human data to investigate the co-evolution of TAb and LCRs through ancestral reconstructions and model inference using an approximate Bayesian calculation based method. We observe that on short evolutionary timescales TAb evolution is significantly impacted by changes in LCR length, with insertions driving TAb down. But in contrast, the observed data is best explained by indel rates in LCRs which are unaffected by shifts in TAb. Our work demonstrates a coupling between LCR and TAb evolution, and the utility of incorporating multiple responses into evolutionary analyses.

摘要

蛋白质低复杂度区域(LCRs)是组成上偏向的氨基酸序列,其中许多序列对包含它们的蛋白质具有重要的进化影响。与高复杂度区域相比,它们的突变不稳定,经历更高的插入缺失和取代率。LCRs 还影响其蛋白质的表达,可能通过从基因转录到翻译再到最终蛋白质降解的过程中的多种影响。已经观察到,尽管蛋白质丰度较低,但包含 LCRs 的蛋白质与转录本丰度(TAb)升高有关。我们收集并整合了人类数据,通过基于近似贝叶斯计算的方法进行祖先重建和模型推断,研究了 TAb 和 LCRs 的共同进化。我们观察到,在短的进化时间尺度上,LCR 长度的变化对 TAb 进化有显著影响,插入会导致 TAb 降低。但是相比之下,观察到的数据最好用 LCR 中的插入缺失率来解释,而插入缺失率不受 TAb 变化的影响。我们的工作证明了 LCR 和 TAb 进化之间的耦合,以及将多种反应纳入进化分析的实用性。

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