唧唧堂编辑二朵2013-12-29 5:18 AM

On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE 有关电视机的不朽:ENCODE无需进化之福音下的人类基因组中的功能

Abstract A recent slew of ENCODE Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is under 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 – 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these “functional” regions, or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used “causal role” definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as “affirming the consequent,” by failing to appreciate the crucial difference between “junk DNA” and “garbage DNA,” by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten. 论文摘要 最近的一系列ENCODE协会出版物,特别是已由所有联盟成员签署了的文章提出人类基因组的80 %以上都具有功能性这一观点;而当前的估计认为通过纯化选择而在进化上高度保存的基因组部分应该低于10%。毫无疑问,提出的这种新观点是对当前估计发起的公然挑战。因此,根据ENCODE协会(的观点),生物学功能可以通过无期限不参与选择的方式而得以保持,这意味着基因组中至少70%在面对有害突变时是完美地无懈可击的。或者是因为任何突变甚至无法在这些“功能性”的区域内发生,或者是因为任何突变甚至在这些区域内都无害。这种荒谬的结论是通过各种不同的手段比如主要是通过利用极少使用的“因果关系”这一生物功能的定义,然后把它不一致地应用到不同的生化特性中,或是通过赞同广为人知的逻辑谬论比如“肯定后者”的方法,或是通过无法鉴别“无用DNA ”和“垃圾DNA ”之间的关键区别,或是通过屈服于功能性的偏倚误差和膨胀估计的分析方法等手段而得出的。在这里,我们详述了在人类基因组中涉及到给几乎每个核苷酸指派功能时出现的许多逻辑性和方法论的一再谬误。ENCODE协会的作者之一预测该研究结果将使得教科书必须被改写。我们也认同许多涉及市场营销,大众媒体炒作和公关的教学书可能都需要被重写。

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