Biology & Philosophy

, Volume 29, Issue 6, pp 807–831 | Cite as

Junk or functional DNA? ENCODE and the function controversy

  • Pierre-Luc GermainEmail author
  • Emanuele Ratti
  • Federico Boem


In its last round of publications in September 2012, the Encyclopedia Of DNA Elements (ENCODE) assigned a biochemical function to most of the human genome, which was taken up by the media as meaning the end of ‘Junk DNA’. This provoked a heated reaction from evolutionary biologists, who among other things claimed that ENCODE adopted a wrong and much too inclusive notion of function, making its dismissal of junk DNA merely rhetorical. We argue that this criticism rests on misunderstandings concerning the nature of the ENCODE project, the relevant notion of function and the claim that most of our genome is junk. We argue that evolutionary accounts of function presuppose functions as ‘causal roles’, and that selection is but a useful proxy for relevant functions, which might well be unsuitable to biomedical research. Taking a closer look at the discovery process in which ENCODE participates, we argue that ENCODE’s strategy of biochemical signatures successfully identified activities of DNA elements with an eye towards causal roles of interest to biomedical research. We argue that ENCODE’s controversial claim of functionality should be interpreted as saying that 80 % of the genome is engaging in relevant biochemical activities and is very likely to have a causal role in phenomena deemed relevant to biomedical research. Finally, we discuss ambiguities in the meaning of junk DNA and in one of the main arguments raised for its prevalence, and we evaluate the impact of ENCODE’s results on the claim that most of our genome is junk.


Biological function Causal role Selected effect ENCODE Junk DNA 



We wish to acknowledge Fridolin Groß, who was part of the many discussions at the origin of this paper and carefully commented several versions of the paper. In addition, we wish to thank all those who have read drafts of this paper: Michel Morange, Michael Weisberg, Iros Barozzi, Lorenzo Del Savio, Marcel Weber and the lgBIG group in Geneva (in which the paper was discussed), Alkistis Elliot-Graves and Vera Pendino. We are also thankful to our colleagues of the FOLSATEC programme. Finally, we wish to acknowledge the two anonymous reviewers for their help in improving the text.


  1. Agency for Healthcare Research and Quality (2001) Reducing and preventing adverse drug events to decrease hospital costs: research in action, issue 1. Retrieved from
  2. Bechtel W, Richardson RC (2010) Discovering complexity—decomposition and localization as strategies in scientific research. The MIT Press, CambridgeGoogle Scholar
  3. Bigelow J, Pargetter R (1987) Functions. J Philos 84(4):181–196CrossRefGoogle Scholar
  4. Birney E (2012a) Lesson for big-data projects. Nature 489:49–51CrossRefGoogle Scholar
  5. Birney E (2012b) ENCODE: my own thoughts. Ewan's Blog: Bioinformatician at large. Retrieved September 5, 2012, from
  6. Brenner S (1998) Refuge of spandrels. Curr Biol 8:R669CrossRefGoogle Scholar
  7. Brown D, Boytchev H (2012) “Junk DNA” concept debunked by new analysis of human genome. The Washington Post. Retrieved September 5, 2012, from
  8. Bunzl M (1980) Comment on “health as a theoretical concept”. Philos Sci 47:116–118CrossRefGoogle Scholar
  9. Chanock SJ (2012) Toward mapping the biology of the genome. Genome Res 22(9):1612–1615. doi: 10.1101/gr.144980.112 CrossRefGoogle Scholar
  10. Comings DE (1972) The structure and function of chromatin. Adv Human Genetics 3:237–431 Google Scholar
  11. Connor S (2003) Glaxo chief: our drugs do not work on most patients. The Independent. Retrieved December 8, 2003, from
  12. Craver C (2007) Explaining the brain: mechanisms and the mosaic unity of neuroscience. Oxford University Press, New YorkCrossRefGoogle Scholar
  13. Cummins R (1975) Functional analysis. J Philos 72(20):741–765CrossRefGoogle Scholar
  14. Darden L (2006) Reasoning in biological discoveries. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  15. Diep F (2013) Friction over function: scientists clash on the meaning of ENCODE’s genetic data. Scientific American. Retrieved April 12, 2013, from
  16. Doolittle WF (2013) Is junk DNA bunk? A critique of ENCODE. Proc Natl Acad Sci USA 110(14):5294–5300. doi: 10.1073/pnas.1221376110 CrossRefGoogle Scholar
  17. Eddy SR (2012) The C-value paradox, junk DNA and ENCODE. Curr Biol 22:R898–R899. doi: 10.1016/j.cub.2012.10.002 CrossRefGoogle Scholar
  18. Eddy SR (2013) The ENCODE project: missteps overshadowing a success. Curr Biol 23:R259–R261. doi: 10.1016/j.cub.2013.03.023 CrossRefGoogle Scholar
  19. Gaudillière JP, Rheinberger H-J (2004) From molecular genetics to genomics, the mapping cultures of twentieth-century genetics. Routledge, LondonCrossRefGoogle Scholar
  20. Gerstein MB, Kundaje A, Hariharan M, Landt SG, Koon-Kiu Y, Chao C et al (2012) Architecture of the human regulatory network derived from ENCODE data. Nature 489:91–100. doi: 10.1038/nature11245 CrossRefGoogle Scholar
  21. Gissis SB, Jablonka E (eds) (2011) Transformations of lamarckism. From subtle fluids to molecular biology. MIT Press, CambridgeGoogle Scholar
  22. Graur D (2013) The Origin of Junk DNA: A Historical Whodunnit. Judge Starling. Retrieved October 19, 2013, from
  23. Graur D, Zheng Y, Price N, Azevedo RBR, Zufall RA, Elhaik E (2013) On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE. Genome Biol Evol 5:578–590. doi: 10.1093/gbe/evt028 Google Scholar
  24. Gregory TR (2007) The onion test. Genomicron, April 27th 2007, retrieved from
  25. Griffiths PE (1993) Functional analysis and proper functions. Br J Philos Sci 44(3):409–422. doi: 10.1093/bjps/44.3.409 CrossRefGoogle Scholar
  26. Griffiths PE (2001) Genetic information: a metaphor in search of a theory. Philos Sci 68(3):394–412CrossRefGoogle Scholar
  27. Griffiths PE (2009) In what sense does “nothing make sense except in the light of evolution”? Acta Biotheor 57:11–32. doi: 10.1007/s10441-008-9054-9 CrossRefGoogle Scholar
  28. Ibarra-Laclette E, Lyons E, Hernández-Guzmán G, Pérez-Torres CA, Carretero-Paulet L, Chang T-H, Herrera-Estrella L (2013) Architecture and evolution of a minute plant genome. Nature 498(7452):94–98. doi: 10.1038/nature1213 CrossRefGoogle Scholar
  29. Kauffman S (1993) The origins of order: self-organization and selection in evolution. Oxford University Press, OxfordGoogle Scholar
  30. Kauffman S (1996) At home in the universe: the search for the laws of self-organization and complexity. Oxford University Press, OxfordGoogle Scholar
  31. Kentikelenis A, Karanikolos M, Papanicolas I, Basu S, McKee M, Stuckler D (2011) Health effects of financial crisis: omens of a Greek tragedy. Lancet 378:1457–1458CrossRefGoogle Scholar
  32. Kolata G (2012) Bits of mystery DNA, far from “Junk,” play crucial role. The New York Times. p. 5–7. Retrieved September 6, 2012, from
  33. Laland KN, Sterelny K, Odling-Smee J, Hoppitt W, Uller T (2011) Cause and effect in biology revisited: is Mayr’s proximate-ultimate dichotomy still useful? Science 334:1512–1516. doi: 10.1126/science.1210879 CrossRefGoogle Scholar
  34. Lynch VJ, Leclerc RD, May G, Wagner GP (2011) Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals. Nat Genetics 43(11):1154–1159. doi: 10.1038/ng.917 CrossRefGoogle Scholar
  35. Maher B (2012) The human encyclopaedia. Nature 486:46–48CrossRefGoogle Scholar
  36. Makalowski W (2003) Not junk after all. Science 300(5623):1246–1247. doi: 10.1126/science.1085690 CrossRefGoogle Scholar
  37. Mayr E (1961) Cause and effect in biology. Science 134(3489):1501–1506. doi: 10.1126/science.134.3489.1501 CrossRefGoogle Scholar
  38. Millikan RG (1989) In defense of proper functions. Philos Sci 56:288–302CrossRefGoogle Scholar
  39. Neander K (1991) Functions as selected effects. Philos Sci 58:168–184CrossRefGoogle Scholar
  40. NHGRI (2002) National Human Genome Research Institute (2002) Workshop summary: the comprehensive extraction of biological information from genomic sequence, retrieved from
  41. Niu D-K, Jiang L (2013) Can ENCODE tell us how much junk DNA we carry in our genome? Biochem Biophys Res Commun 430:1340–1343. doi: 10.1016/j.bbrc.2012.12.074 CrossRefGoogle Scholar
  42. Nobrega MA, Zhu Y, Plajzer-Frick I, Afzal V, Rubin EM (2004) Megabase deletions of gene deserts result in viable mice. Nature 431:988–993. doi: 10.1038/nature02923.1 CrossRefGoogle Scholar
  43. Ohno S (1970) Evolution by gene duplication. Springer, New YorkGoogle Scholar
  44. Ohno S (1972) So much “junk” DNA in our genome. Brookhaven Symp Biol 23:366–370Google Scholar
  45. Ohno S (1973) Evolutionary reason for having so much junk DNA. In: Pfeiffer RA (ed) Modern aspects of cytogenetics: constitutive heterochromatin in man. F.K. Schattauer Verlag, StuttgartGoogle Scholar
  46. Pennisi E (2012) ENCODE project writes eulogy for junk DNA. Science 337:1159–1161CrossRefGoogle Scholar
  47. Pigliucci M, Müller GB (eds) (2010) Evolution—the extended synthesis. The MIT Press, CambridgeGoogle Scholar
  48. Ponting CP, Hardison RC (2011) What fraction of the human genome is functional? Genome Res 21:769–1776. doi: 10.1101/gr.116814.110 CrossRefGoogle Scholar
  49. Pritchard JK, Gilard Y (2012) Evolution and the code. Nat (News & Views) 489:55Google Scholar
  50. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?. Cell 146(3):353–358. doi: 10.1016/j.cell.2011.07.014 Google Scholar
  51. Schaub MA, Boyle AP, Kundaje A, Batzoglou S, Snyder M (2012) Linking disease associations with regulatory information in the human genome. Genome Res 22:1748–1759. doi: 10.1101/gr.136127.111 CrossRefGoogle Scholar
  52. Shapiro JA (2011) Evolution: a view from the 21st century. FT Press, New JerseyGoogle Scholar
  53. Stamatoyannopoulos J (2012) What does our genome encode? Genome Res 22:1602–1611. doi: 10.1101/gr.146506.112 CrossRefGoogle Scholar
  54. Strasser BJ (2008) GenBank—natural history in the 21st century. Science 322(5901):537–538. doi: 10.1126/science.1163399 CrossRefGoogle Scholar
  55. Strasser BJ (2012) Data-driven sciences: from wonder cabinets to electronic databases. Stud Hist Philos Biol Biomed Sci 43:85–87. doi: 10.1016/j.shpsc.2011.10.009 CrossRefGoogle Scholar
  56. The ENCODE Project Consortium (2004) The ENCODE (ENCyclopedia Of DNA Elements) project. Science 306:636–640. doi: 10.1126/science.1105136 CrossRefGoogle Scholar
  57. The ENCODE Project Consortium (2011) A user’s guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 9(4):e1001046. doi: 10.1371/journal.pbio.1001046 CrossRefGoogle Scholar
  58. The ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74. doi: 10.1038/nature11247 CrossRefGoogle Scholar
  59. Tinbergen N (1963) On aims and methods in ethology. Zeitschrift für Tierpsychologie 20(4):410–433CrossRefGoogle Scholar
  60. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K et al (2011) SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 365:2497–2506. doi: 10.1056/NEJMoa1109016 CrossRefGoogle Scholar
  61. Weber M (2005) Philosophy of experimental biology. Cambridge University Press, CambridgeGoogle Scholar
  62. Wouters AG (2003) Four notions of biological function. Stud Hist Philos Sci Part C Stud Hist Philos Biol Biomed Sci 34:633–668. doi: 10.1016/j.shpsc.2003.09.006 CrossRefGoogle Scholar
  63. Wright L (1973) Functions. Philos Rev 82(2):139–168CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Pierre-Luc Germain
    • 1
    • 2
    Email author
  • Emanuele Ratti
    • 1
    • 2
  • Federico Boem
    • 1
    • 2
  1. 1.Department of Experimental OncologyEuropean Institute of Oncology (IEO)MilanItaly
  2. 2.Dipartimento di Scienze Della SaluteUniversità degli Studi di MilanoMilanItaly

Personalised recommendations