The latest round of ENCODE papers are out, accessible via a handy ENCODE explorer gateway at Nature. I know what I’ll be doing for the next week. Stay tuned for more Finch & Pea coverage of what all this means, but I can’t resist a few brief comments about function.
First, you can immediately dismiss the NY Times’s misleading headline that suggests much, much more of the genome is functional than we previously thought. Being an intron counts as ‘function’ here, which is a pretty low bar to meet. The ENCODE results indicate that much of the genome is represented within introns, which I find fascinating, but that’s not something that forces us to dramatically revise our ideas about function in the genome.
Second, I’m going to claim (without any proof whatsoever) the title of the world’s record holder for “the largest number of randomly generated DNA sequences tested for function in an enhancer assay.” Hopefully in the not too distant future you can read in print about the 1000+ random sequences (plus several thousand genomic sequences) we tested in our new, smokin’ hot, high-throughput enhancer assay, but here’s the punch line: it’s not that difficult to randomly generate a DNA sequence that will drive substantial tissue-specific transcription.
In other words, whether it’s been selected for function or not, DNA is generally not biochemically inert.
P.S. This seems to be consistent with Ewan Birney’s comment, “It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be.”
P.P.S. Brief methods: We took sequences under ChIP-seq peaks, thoroughly scrambled them while preserving the original di-nucleotide frequencies, and dropped them upstream of a basal promoter to test for enhancer activity.
The Finch and Pea 