deeper genome book coverJohn Parrington is an associate professor in molecular and cellular pharmacology at the University of Oxford. In The Deeper Genome, he provides an elegant, accessible account of the profound and unexpected complexities of the human genome, and shows how many ideas developed in the 20th century are being overturned.

Over a decade ago, as the Human Genome Project completed its mapping of the entire human genome, hopes ran high that we would rapidly be able to use our knowledge of human genes to tackle many inherited diseases, and understand what makes us unique among animals. But things didn’t turn out that way. Things have changed since those early heady days of the Human Genome Project. But the emerging picture is if anything far more exciting.

Take DNA. It’s no simple linear code, but an intricately wound, 3D structure that coils and uncoils as its genes are read and spliced in myriad ways. Forget genes as discrete, protein-coding “beads on a string”: only a tiny fraction of the genome codes for proteins, and anyway, no one knows exactly what a gene is any more.

A key driver of this new view is ENCODE, the Encyclopedia of DNA Elements, which is an ambitious international project to identify the functional parts of the human genome. In 2012, it revealed not only that the protein-coding elements of DNA can overlap, but that the 98 per cent of the genome that used to be labelled inactive “junk” is nothing of the sort. Some of it regulates gene activity, some churns out an array of different kinds of RNA molecules (RNAs for short), some tiny, some large, many of whose functions are hotly debated. Parrington quotes ENCODE scientist Ewan Birney as saying at the time, “It’s a jungle in there. It’s full of things doing stuff.”

Recent insights into what some of this “stuff” is reveal problems with another classic idea: that DNA is the master controller of the cell, with information flowing in one direction from it, via RNA, to proteins. Some of ENCODE’s mystery RNAs control gene activity, others make changes that the cell remembers and passes on when it divides, and which can even be passed down generations. The RNAs may be one way the environment alters the behavior of genes without changing their DNA sequences, a phenomenon known as epigenetics.

Growing evidence of the extent of epigenetic influence on the genome has led some researchers to argue that much of medical research, and indeed mainstream evolutionary theory, places too much importance on genes in determining an organism’s characteristics. They think the environment plays a much bigger role in their emergence as an organism develops.

John ParringtonJohn Parrington is a University Lecturer in Molecular and Cellular Pharmacology at the University of Oxford, and a Tutorial Fellow in Medicine at Worcester College, Oxford. He has published over 70 peer-reviewed articles in science journals including Nature, Current Biology, Journal of Cell Biology, Journal of Clinical Investigation, Development, Developmental Biology, and Human Reproduction. He has extensive experience writing popular science, having published articles in The Guardian, New Scientist, Chemistry World, and The Biologist. As a British Science Association Media Fellow he worked as a science journalist at The Times for 7 weeks where he published 22 articles. He has also written science reports for the public for the Wellcome Trust, British Council, and Royal Society.

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