The human genome and the immortality of television sets

The ENCODE project (its stated goal is “to identify all functional elements in the human genome sequence“) has attracted much criticism. Dan Graur, a member of the Luxuriant Former Hair Club for Scientists (LFHCfS), and his colleagues made hearty contributions to that river of criticism:

On the immortality of television sets: ‘function’ in the human genome according to the evolution-free gospel of ENCODE,” Dan Graur, Yichen Zheng, Nicholas Price, Ricardo BR Azevedo, Rebecca A. Zufall, and Eran Elhaik, Genome Biology and Evolution, vol. 5, no. 3, 2013, pp. 578-590.  The authors write:

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….

 “I would be quite proud to have served on the committee that designed the E. coli genome. There is, however, no way that I would admit to serving on a committee that designed the human genome. Not even a university committee could botch something that badly.” —David Penny (personal communication) …

“The onion test is a simple reality check for anyone who thinks they can assign a function to every nucleotide in the human genome. Whatever your proposed functions are, ask yourself this question: Why does an onion need a genome that is about five times larger than ours?” —T. Ryan Gregory (personal communication) …

The absurd alternative, which unfortunately was adopted by ENCODE, is to assume that no deleterious mutations can ever occur in the regions they have deemed to be functional. Such an assumption is akin to claiming that a television set left on and unattended will still be in working condition after a million years because no natural events, such as rust, erosion, static electricity, and earthquakes can affect it. The convoluted rationale for the decision to discard evolutionary conservation and constraint as the arbiters of functionality put forward by a lead ENCODE author (Stamatoyannopoulos 2012) is groundless and self-serving.