Institute for Molecular Bioscience, University of Queensland, 306 Carmody Road, St Lucia, QLD 4072, Australia.
Biochimie. 2011 Nov;93(11):2013-8. doi: 10.1016/j.biochi.2011.07.018. Epub 2011 Jul 23.
Increasing numbers of transcripts have been reported to transmit both protein-coding and regulatory information. Apart from challenging our conception of the gene, this observation raises the question as to what extent this phenomenon occurs across the genome and how and why such dual encoding of function has evolved in the eukaryotic genome. To address this question, we consider the evolutionary path of genes in the earliest forms of life on Earth, where it is generally regarded that proteins evolved from a cellular machinery based entirely within RNA. This led to the domination of protein-coding genes in the genomes of microorganisms, although it is likely that RNA never lost its other capacities and functionalities, as evidenced by cis-acting riboswitches and UTRs. On the basis that the subsequent evolution of a more sophisticated regulatory architecture to provide higher levels of epigenetic control and accurate spatiotemporal expression in developmentally complex organisms is a complicated task, we hypothesize: (i) that mRNAs have been and remain subject to secondary selection to provide trans-acting regulatory capability in parallel with protein-coding functions; (ii) that some and perhaps many protein-coding loci, possibly as a consequence of gene duplication, have lost protein-coding functions en route to acquiring more sophisticated trans-regulatory functions; (iii) that many transcripts have become subject to secondary processing to release different products; and (iv) that novel proteins have emerged within loci that previously evolved functionality as regulatory RNAs. In support of the idea that there is a dynamic flux between different types of informational RNAs in both evolutionary and real time, we review recent observations that have arisen from transcriptomic surveys of complex eukaryotes and reconsider how these observations impact on the notion that apparently discrete loci may express transcripts with more than one function. In conclusion, we posit that many eukaryotic loci have evolved the capacity to transact a multitude of overlapping and potentially independent functions as both regulatory and protein-coding RNAs.
越来越多的转录本被报道既能传递蛋白编码信息，也能传递调控信息。除了对我们的基因概念提出挑战之外，这一观察结果还引发了一个问题，即在多大程度上这种现象发生在整个基因组中，以及这种功能的双重编码是如何以及为什么在真核生物基因组中进化的。为了解决这个问题，我们考虑了地球上最早形式的生命中基因的进化路径，在那里，人们普遍认为蛋白质是从完全基于 RNA 的细胞机制中进化而来的。这导致了蛋白编码基因在微生物基因组中的主导地位，尽管 RNA 可能从未失去其其他能力和功能，这一点可以从顺式作用的核酶和 UTRs 中得到证明。基于这样一种观点，即更复杂的调控架构的后续进化是一项复杂的任务，它为发育复杂的生物体提供更高水平的表观遗传控制和精确的时空表达，我们假设：(i)mRNA 一直并且仍然受到二次选择的影响，以提供与蛋白编码功能并行的转录调节能力；(ii)一些，也许是许多蛋白编码基因座，可能是由于基因复制，在获得更复杂的转录调控功能的过程中失去了蛋白编码功能；(iii)许多转录本已经成为二次加工的对象，以释放不同的产物；(iv)在以前作为调节 RNA 进化功能的基因座中出现了新的蛋白质。为了支持在进化和实时过程中不同类型的信息性 RNA 之间存在动态流动的观点，我们回顾了最近从复杂真核生物的转录组调查中出现的观察结果，并重新考虑这些观察结果如何影响这样一种观点，即显然离散的基因座可能表达具有多种功能的转录本。总之，我们假设许多真核生物基因座已经进化出作为调节和蛋白编码 RNA 同时发挥多种重叠和潜在独立功能的能力。
