On the Immortality of Television Sets: "Function" in the Human Genome According to the Evolution-Free Gospel of ENCODE

Abstract

A recent slew of ENCyclopedia Of DNA Elements (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 less than 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.

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

“…The rapid spread of introns in eukaryotes has been ascribed to group II introns after they were imported by endosymbionts (CavalierSmith 1991), perhaps necessitating the separation of slow mRNA production in the nucleus from the fast translation in the cytoplasm, one of the hallmarks of the eukaryotic cell (Martin and Koonin 2006). 2 Importantly, the process of continuously converting RNA to DNA and its genomic integration has the potential to grossly inflate genomes with neutrally evolving material and, in conjunction with larger deletion of segments by recombination, leads to a high turnover rate of sequences on an evolutionary time scale, once more calling into question the ENCODE claim that 80% of the human genome is functional (Doolittle 2013;Graur et al 2013;Niu and Jiang 2013). Generally, specific retroposons 3 become active in certain lineages, and reverse transcripts from one or several master gene transcripts, such as LINEs (long interspersed elements), autonomous as they harbor gene encoding the retroposition machinery such as reverse transcriptase and nonautonomous SINEs (short interspersed elements), such as Alu or B1 elements.…”

‘Satellite DNA transcripts have diverse biological roles in Drosophila’

“…In fact, satDNAs have been barely mentioned in most papers reporting whole-sequenced genomes, despite their obvious high representativeness in the genome of many organisms (430%) and transcriptional activity (Pezer et al, 2011). Although transcription alone does not directly imply function (Graur et al, 2013), the biological status of such transcripts remained unclear until very recently.…”

L’apophénie d’ENCODE ou Pangloss examine le génome humain

“…Dan Graur s'est fait le champion des pourfendeurs des inepties propagées à grande échelle autour de cette découverte. Adepte d'un humour grinçant, auteur de chroniques hilarantes sur la « BIG » science en général et ENCODE en particulier sur son blog dont nous conseillons vivement la lecture 1 , il écrivit en 2013 un article très caustique [11] qui ramena la découverte faite par ENCODE à ce qu'elle est : un affichage publicitaire. En 2014, nouvelle livraison d'articles par le consortium ENCODE dans la prestigieuse revue Nature.…”

“…On peut retracer cette histoire en étudiant la s'interroge sur les raisons de cette retenue d'ENCODE. S'agit-il de donner un air plus scientifique à cette « découverte » ou de laisser un peu d'espace pour les concepts éculés de la biologie évolutive [11] ?…”