Gerstein Mark B, Bruce Can, Rozowsky Joel S, Zheng Deyou, Du Jiang, Korbel Jan O, Emanuelsson Olof, Zhang Zhengdong D, Weissman Sherman, Snyder Michael
Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06511, USA.
Genome Res. 2007 Jun;17(6):669-81. doi: 10.1101/gr.6339607.
While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century--from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition side-steps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.
虽然人类基因组测序揭示的蛋白质编码基因数量让我们感到惊讶，但它并没有从根本上改变我们对基因的看法。相比之下，ENCODE计划发现的分散调控和广泛转录的复杂模式，以及非基因保守性和非编码RNA基因的丰富性，对基因的概念提出了挑战。为了说明这一点，我们回顾了过去一个世纪基因操作定义的演变——从孟德尔和摩根的遗传抽象元素到序列数据库中列举的当今开放阅读框。然后我们总结了ENCODE目前的研究结果，并为这种复杂性提供了一个计算隐喻。最后，我们提出了对基因定义的初步更新：基因是编码一组连贯的、可能重叠的功能产物的基因组序列的联合体。我们的定义通过将调控完全排除在定义之外，并主张应使用最终的功能性基因产物（而非中间转录本）来将与单个基因相关的实体归为一组，从而避开了调控和转录的复杂性。它还体现了生物学功能概念在定义基因时的不可或缺性。
