Published: Jan 2017
Updated: April 1, 2024

Comment on:

The Extent of Functionality in the Human Genome

John Mattick and Martin Dinger.  HUGO.  2013.

In July 2013, biochemist John Mattick and John Dinger responded to claims raised by several ENCODE critics. On the C-Value paradox:

However, where data is available, these upward exceptions appear to be due to polyploidy and/or varying transposon loads (of uncertain biological relevance), rather than an absolute increase in genetic complexity

On level of function, they noted:

the vast majority of the mammalian genome is differentially transcribed in precise cell-specific patterns to produce large numbers of intergenic, interlacing, antisense and intronic non-protein-coding RNAs, which show dynamic regulation in embryonal development, tissue differentiation and disease, with even regions superficially described as ‘gene deserts’ expressing specific transcripts in particular cells. Moreover, there is increasing evidence of their functional relevance and that a major function of these noncoding RNAs is to guide chromatin-modifying complexes to their sites of action, to supervise the epigenetic trajectories of development... we would submit that differential expression (including extensive alternative splicing) of RNAs is a far more accurate guide to the functional content of the human genome than logically circular assessments of sequence conservation, or lack thereof.  Assertions that the observed transcription represents random noise (tacitly or explicitly justified by reference to stochastic (‘noisy’) firing of known, legitimate promoters in bacteria and yeast), is more opinion than fact and difficult to reconcile with the exquisite precision of differential cell- and tissue-specific transcription in human cells. Moreover, where tested, these noncoding RNAs usually show evidence of biological function in different developmental and disease contexts, with, by our estimate, hundreds of validated cases already published and many more en route, which is a big enough subset to draw broader conclusions about the likely functionality of the rest.  It is also consistent with the specific and dynamic epigenetic modifications across most of the genome, and concurs with the ENCODE conclusion that 80% of the genome shows biochemical indices of function

They also accuses critic Dan Graur of being motivated by an anti-ID bias:

There may also be another factor motivating the Graur et al. and related articles (van Bakel et al. 2010; Scanlan 2012), which is suggested by the sources and selection of quotations used at the beginning of the article, as well as in the use of the phrase “evolution-free gospel” in its title (Graur et al. 2013): the argument of a largely non-functional genome is invoked by some evolutionary theorists in the debate against the proposition of intelligent design of life on earth, particularly with respect to the origin of humanity. In essence, the argument posits that the presence of non-protein-coding or so-called ‘junk DNA’ that comprises >90% of the human genome is evidence for the accumulation of evolutionary debris by blind Darwinian evolution, and argues against intelligent design, as an intelligent designer would presumably not fill the human genetic instruction set with meaningless information (Dawkins 1986; Collins 2006). This argument is threatened in the face of growing functional indices of noncoding regions of the genome, with the latter reciprocally used in support of the notion of intelligent design and to challenge the conception that natural selection accounts for the existence of complex organisms (Behe 2003; Wells 2011).