State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing, China.
College of Biology, Hunan University, Changsha, China.
Nat Commun. 2021 Feb 17;12(1):1076. doi: 10.1038/s41467-021-21394-y.
Upstream open reading frames (uORFs) play widespread regulatory functions in modulating mRNA translation in eukaryotes, but the principles underlying the genomic distribution and evolution of uORFs remain poorly understood. Here, we analyze ~17 million putative canonical uORFs in 478 eukaryotic species that span most of the extant taxa of eukaryotes. We demonstrate how positive and purifying selection, coupled with differences in effective population size (N), has shaped the contents of uORFs in eukaryotes. Besides, gene expression level is important in influencing uORF occurrences across genes in a species. Our analyses suggest that most uORFs might play regulatory roles rather than encode functional peptides. We also show that the Kozak sequence context of uORFs has evolved across eukaryotic clades, and that noncanonical uORFs tend to have weaker suppressive effects than canonical uORFs in translation regulation. This study provides insights into the driving forces underlying uORF evolution in eukaryotes.
上游开放阅读框 (uORFs) 在调节真核生物 mRNA 翻译方面发挥着广泛的调控作用，但 uORFs 的基因组分布和进化背后的原理仍知之甚少。在这里，我们分析了 478 个真核物种中约 1700 万个推定的典型 uORFs，这些物种涵盖了真核生物现存的大部分分类群。我们展示了正选择和纯化选择，以及有效种群大小 (N) 的差异，是如何塑造真核生物中 uORFs 的内容的。此外，基因表达水平在影响物种中基因 uORF 的发生方面也很重要。我们的分析表明，大多数 uORFs 可能发挥调节作用，而不是编码功能肽。我们还表明，uORFs 的 Kozak 序列上下文在真核类群中发生了进化，并且非典型 uORFs 在翻译调控中往往比典型 uORFs 的抑制作用弱。这项研究为真核生物 uORF 进化的驱动力提供了深入了解。
