How to Frame a Null Hypothesis

A reader has alerted me to an article by Michael White at Adaptive Complexity: Genomic Junk and Transcriptional Noise.

With hot, new technologies, biologists are taking higher-resolution snapshots of what's going on inside the cell, but the results are stirring up controversy. One of the most interesting recent discoveries is that transcription is everywhere: DNA is transcribed into RNA all over the genome, even DNA that has long been thought to have a non-functional role. What is all of this transcription for? Does the 'dark matter' of the genome have some cryptic, undiscovered function?

Unfortunately, in all of the excitement over possible new functions, many biologists have forgotten how to frame a null hypothesis - the default scenario that you expect to see if there is no function to this transcribed DNA. As a result, the literature is teeming with wild, implausible speculation about how our excess DNA might be beneficial to us.

So here, let's step back and look at what we expect from DNA when it's playing absolutely no functional role; in other words, let's look at the null hypothesis of genomic junk and transcriptional noise. We can then take our null hypothesis and use it to look at a fascinating new study of how genomic parasites sculpt transcription in our cells.

If you are interested in what's wrong with science these days then you must read his article.

The point is not whether you believe that all transcription is adaptive and functional, or whether you believe that most of it is noise. The real point is that it is very bad science to ignore the null hypothesis and publish naive speculation as if it were the only possible explanation.

Whenever you see a paper that fails to address the null hypothesis you can be sure that you are reading bad science. Everything else in the paper is suspect.

The key fact that most scientists are overlooking is that RNA polymerase and the various transcription factors must bind non-specifically at thousands of sites in a random sequence of junk DNA. This is just basic biochemistry of the sort that should be taught in undergraduate classes. Transcription will be initiated by accident at some of these sites even though they are not functional promoters. Again, this is basic biochemistry.

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[Image Credit: Horton et al. Principles of Biochemistry 4/e p.657]