Is junk DNA bunk? A critique of encode

Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4R2.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 03/2013; 110(14). DOI: 10.1073/pnas.1221376110
Source: PubMed


Do data from the Encyclopedia Of DNA Elements (ENCODE) project render the notion of junk DNA obsolete? Here, I review older arguments for junk grounded in the C-value paradox and propose a thought experiment to challenge ENCODE's ontology. Specifically, what would we expect for the number of functional elements (as ENCODE defines them) in genomes much larger than our own genome? If the number were to stay more or less constant, it would seem sensible to consider the rest of the DNA of larger genomes to be junk or, at least, assign it a different sort of role (structural rather than informational). If, however, the number of functional elements were to rise significantly with C-value then, (i) organisms with genomes larger than our genome are more complex phenotypically than we are, (ii) ENCODE's definition of functional element identifies many sites that would not be considered functional or phenotype-determining by standard uses in biology, or (iii) the same phenotypic functions are often determined in a more diffuse fashion in larger-genomed organisms. Good cases can be made for propositions ii and iii. A larger theoretical framework, embracing informational and structural roles for DNA, neutral as well as adaptive causes of complexity, and selection as a multilevel phenomenon, is needed.

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    • "In this debate, scientists frequently refer to philosophical positions in support of their claims (Wouters 2003). For instance, a number of papers attacking the conclusion of the ENCODE project that most of the genomic DNA is functional refer to the Selected Effect (SE) concept of function in their refutation of this claim (Graur et al. 2013; Doolittle 2013; Eddy 2013). The SE concept of function defines the function of an item or trait as the effect for which it was selected by natural selection or by which it is maintained (Wright 1973; Millikan 1989; Neander 1991; Griffiths 1993). "
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    ABSTRACT: Function is a central concept in biological theories and explanations. Yet discussions about function are often based on a narrow understanding of biological systems and processes, such as idealized molecular systems or simple evolutionary, i.e., selective, dynamics. Conflicting conceptions of function continue to be used in the scientific literature to support certain claims, for instance about the fraction of "functional DNA" in the human genome. Here we argue that all biologically meaningful interpretations of function are necessarily context dependent. This implies that they derive their meaning as well as their range of applicability only within a specific theoretical and measurement context. We use this framework to shed light on the current debate about functional DNA and argue that without considering explicitly the theoretical and measurement contexts all attempts to integrate biological theories are prone to fail.
    Theory in Biosciences 10/2015; DOI:10.1007/s12064-015-0215-5 · 1.23 Impact Factor
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    • "all experimentally defined regulatory elements are expected to be functionally or phenotypically significant (Eddy 2012; Doolittle 2013; Graur et al. 2013; Niu and Jiang 2013). Thus, we hypothesized that the synergistic combination of comparative and functional genomics would facilitate the highresolution identification of conserved and human accelerated regulatory sequences. "
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    ABSTRACT: It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives.
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    • "In thus extending the upper bounds of an undifferentiated " functionality " into territory occupied by TEs without acknowledging that there are other (genome level) selective processes at play to explain the presence of so much DNA, ENCODE investigators dismiss much previous theory in genome evolution (Doolittle 2013; Palazzo and Gregory 2014; Elliott et al. 2014). Some ENCODE supporters even claim to have at last exposed ignorant and possibly willful bias on the part of evolutionary theorists who have argued for junk and selfish DNA. "
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    ABSTRACT: One of several issues at play in the renewed debate over "junk DNA" is the organizational level at which genomic features might be seen as selected, and thus to exhibit function, as etiologically defined. The intuition frequently expressed by molecular geneticists that junk DNA is functional because it serves to "speed evolution" or as an "evolutionary repository" could be recast as a claim about selection between species (or clades) rather than within them, but this is not often done. Here we review general arguments for the importance of selection at levels above that of organisms in evolution, and develop them further for a common genomic feature: the carriage of transposable elements (TEs). In many species, not least our own, TEs comprise a large fraction of all nuclear DNA, and whether they individually or collectively contribute to fitness - or are instead junk - is a subject of ongoing contestation. Even if TEs generally owe their origin to selfish selection at the lowest level (that of genomes), their prevalence in extant organisms and the prevalence of extant organisms bearing them must also respond to selection within species (on organismal fitness) and between species (on rates of speciation and extinction). At an even higher level, the persistence of clades may be affected (positively or negatively) by TE carriage. If indeed TEs speed evolution, it is at these higher levels of selection that such a function might best be attributed to them as a class. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 08/2015; 7(8). DOI:10.1093/gbe/evv152 · 4.23 Impact Factor
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