Genetics: We are the 98%

Journal name:
Nature
Volume:
520,
Pages:
615–616
Date published:
DOI:
doi:10.1038/520615a
Published online

Nathaniel Comfort unpicks the metaphors in a trio of books exploring the 'junk'-ridden genome.

  • Biocode: The New Age of Genomics

    Oxford Univ. Press 2015. ISBN: 9780199687756

    Buy this book: US| UK| Japan

  • The Deeper Genome: Why There Is More to the Human Genome Than Meets the Eye

    Oxford Univ. Press 2015. ISBN: 9780199688739

    Buy this book: US| UK| Japan

  • Junk DNA: A Journey Through the Dark Matter of the Genome

    Icon 2015. ISBN: 9781848318267

    Buy this book: US| UK| Japan

Illustration by Andrea Manzati

The language of DNA is a veritable cornucopia of metaphor and cliché. Since James Watson and Francis Crick solved the double helix, biologists have imagined DNA as an information-storage device: magnetic tape, a computer program or, most commonly, a book that contains the instructions for making a cell's proteins. In multicellular organisms, this precious tome is secured in the vault of the nucleus, the membrane of which isolates and protects nature from nurture.

But if a genome is text, it is badly edited. Most DNA is gibberish, full of stutters, snippets of doggerel from other species, and echoes of quiescent viruses. In humans, only about 2% of the genome encodes proteins. Much — but not all — of the remaining 98% is evolutionary detritus. In the 1960s, researchers learned that non-coding DNA can serve vital functions, such as regulating gene action and building ribosomes. The remainder they began to call junk.

Today, junk DNA is at the heart of the most radical transformation of how we understand the genome since the information metaphor. Three books — The Deeper Genome by John Parrington, Junk DNA by Nessa Carey and Biocode by Dawn Field and Neil Davies — present a vision of the twenty-first-century genome. Their relative success hinges on metaphor and imagery, both in how they conceive the genome and in the writing itself.

In September 2012, the ENCODE (Encyclopedia of DNA Elements) consortium announced that its multi-year international effort to catalogue the various types of DNA sequence had assigned “biochemical function” to 80% of the human genome. Incautious reporters began shouting that junk was bunk, even though scientific consensus maintains that most genomes contain large amounts of it. The subsequent debate upregulated public interest in non-coding DNA — but how do we talk about DNA now?

The title Biocode forestalls any doubt that the authors hew to the information metaphor. Breathlessly, Field and Davies survey the greatest hits and promises of genomics, including Jurassic Park-style reanimation of extinct species, the microbiome and environmental engineering. The thin chapters blurt out strings of recent findings, each capped with a crescendo of sensational speculations that mostly rehearse familiar ethical questions. Critical distance is achieved with the time-honoured double negative: “Might a lawyer one day argue that deliberately not giving [our children] the best genes available is a form of abuse? It is not inconceivable to imagine a world where natural reproduction would seem primitive and even barbaric.” It concludes by exhorting us to set our sights on a global genome project to understand “the software that shapes our living planet”. The biocode is Gaia plus DNA. But two clichés do not make a right. Biocode simply extends the text metaphor to the macrocosm.

The old metaphor is not wrong; it is incomplete. In the new genome, lines of static code have become a three-dimensional tangle of vital string, constantly folding and rearranging itself, responsive to outside input. The roots of this idea run deep. In her 1983 Nobel lecture, geneticist Barbara McClintock called the genome a “sensitive organ of the cell”. McClintock, who discovered mobile genetic elements in the 1940s, had named them controlling elements because she thought they composed the regulatory system that governed gene action. In 1980, Ford Doolittle and Carmen Sapienza proposed that transposons were molecular parasites, jumping into genomes to propagate themselves. Parasitic transposons are now textbook knowledge, but McClintock's larger point holds: the genome is dynamic, full of regulatory elements that respond to environmental cues.

The Deeper Genome is the only book of the three that credits McClintock as a progenitor of the three-dimensional genome. A scientist and journalist, Parrington covered the ENCODE story for The Times in 2012; his book enriches those accounts with historical and scientific context. The science is better than the history. He provides a fine discussion of recent support for McClintock's often-overlooked late work on how stress can activate transposition, but he perpetuates the myth that at first no one thought transposition was real. The contested point was actually McClintock's interpretation of mobile elements as controllers of gene action. Parrington's strongest chapters survey the emerging view of gene regulation, including DNA folding, epigenetics and regulatory RNA. Overall, this is a faithful, engaging portrait of the twenty-first-century genome.

Finally, Junk DNA, like the genome, is crammed with repetitious elements and superfluous text. Bite-sized chapters parade gee-whizz moments of genomics. Carey's The Epigenetics Revolution (Columbia University Press, 2012) offered lucid science writing and vivid imagery. Here the metaphors have been deregulated: they metastasize through an otherwise knowledgeable survey of non-coding DNA. At one point, the reader must run a gauntlet of baseball bats, iron discs, Velcro and “pretty fabric flowers” to understand “what happens when women make eggs”. The genome seems to provoke overheated prose, unbridled speculation and Panglossian optimism. Junk DNA produces a lot of DNA junk.

The idea that the many functions of non-coding DNA make the concept of junk DNA obsolete oversells a body of research that is exciting enough. ENCODE's claim of 80% functionality strikes many in the genome community as better marketing than science.

Still, as with McClintock, the larger point holds: the genome is more than a set of rules and parts descriptions. Finding apt imagery to replace the dead metaphor of the 'instruction book of life' could enable us to break free of the cliché of nature versus nurture. It could usher in a more democratic conception of life, in which all the world's a cell, and all the genes and genomes merely players.

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