The attempts to define genome function have been mired in controversy since ENCODE published its ‘80%’ finding in 2012 (Nature 489, 57-74; 2012). A subsequent paper from the same consortium a few months ago also met with derision, partly because it didn’t even speculate on the fraction of the genome that might have a purpose (M. Kellis et al. Proc. Natl Acad. Sci. USA 111, 6131-6138; 2014). That paper did, however, argue that evolutionary, genetic and biochemical data need to be taken into account to work out the answer.
In the latest report, the Oxford researchers responded to that call by focusing on evolutionary data. They looked for parts of the genome that showed low rates of mutation, a sign that those regions were conserved through natural selection. They classified the sequences – and only those sequences – as functional, a definition that is at odds with that used by ENCODE, which equated biochemical activity with functionality.
The shifting definitions confused some readers. “I don’t get this paper,” tweeted John Greally, an epigeneticist at the Albert Einstein College of Medicine of Yeshiva University in New York City. “Functional=conserved, but discussion acknowledges that function can be in non-conserved sequences?” When reached for further comment, Greally says that he “gets” the paper now, but that he is “still frustrated by the way this debate is causing so much unproductive friction”. More.
Because the official doctrine headsman needs more heads?
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