I complain a lot about the quality of science writing but today's post is very different. I want to highlight an article by Michael Le Page that he just published in New Scientist. It's one of the best articles on junk DNA that I've ever seen in popular science magazines and newspapers [Human-plant hybrid cells reveal truth about dark DNA in our genome].
I've admired Michael Le Page for many years because of his articles on climate change and evolution. It doesn't surprise me that he's right about junk DNA.
Here's part of what he writes...
The main function of DNA is to store the recipes for making proteins, the molecular machines that do almost all the work in cells. The DNA recipes are copied to make messenger RNAs that carry the recipes to ribosomes, the cell’s protein-making factories.
It was initially assumed almost all DNA consists of recipes for making proteins, but we now know that just 1.2 per cent of the human genome codes for proteins. So what does the rest do?
Since the 1960s, many biologists have argued that it is mostly junk. Yes, a small percentage of non-protein-coding DNA is really important and we are likely to keep discovering bits that do useful things for decades, but such discoveries, they say, won’t change the overall picture of the vast majority of non-coding DNA being junk.
For instance, a 2011 study found that only around 5 per cent of the genome is conserved over deep time – evolution doesn’t seem to care about the rest of it. Biologists in the mostly-junk camp also point out that the size of genomes varies wildly between species. Why does an onion need five times as much DNA as a human, for instance? Why does the lungfish have 30 times as much?
Michael knows that the ENCODE results have been challenged by many scientists who believe that the "activity" detected by ENCODE researchers does not always demonstrate function. He also knows that Sean Eddy proposed the random genome project1 as a way testing ENCODE's conclusion. The idea is to insert a large amount of random sequence DNA into human cells and see if you can detect transcription factor binding sites and spurious transcription. The prediction is that the random sequence DNA will be full of the same kind of "activity" reported by ENCODE and this will demonstrate that it is spurious activity that does not represent true biological function.
There have been a few papers on the activity of small pieces of random sequence DNA and they confirm Sean's prediction that such sequences have ENCODE activity. But Michael Le Page writes about a more extensive test that hasn't yet been published.
He talked to Brett Adey and Austen Ganley at the University of Auckland in New Zealand. Like many others, they were aware of the ENCODE results but thought that, "A large amount can simply be explained by background noise. This seems to be broadly consistent with the junk DNA idea." When they learned that a group in Japan had created a human cell line containing 35 million base pairs of plant DNA, they realized that this could be a good test of Sean's random genome project because plant DNA won't contain the kind of regulatory sequences found in humans. It is effectively random sequence DNA.
After initial studies to check the plant DNA is indeed effectively random, as far as the human cell is concerned, Adey and Ganley then measured the number of starting points for turning DNA into RNA per 1000 base pairs of non-coding DNA.
If DNA being turned into RNA really is a sign of function, then hardly any plant DNA should be turned into RNA. In reality, Adey and Ganley found only slightly less activity – there were around 80 per cent as many start sites per kilobase of non-coding A. thaliana DNA compared with human non-coding DNA.
In other words, this strongly suggests that almost all the activity seen by ENCODE is noise.
Michael Le Page interviewed the right people (Sean Eddy, Chris Ponting, Dan Graur) in order to get knowledgeable comments on the significance of this result. As usual, he got the best quote from Dan Graur.
This very elegant study was needed. It offers yet more experimental evidence confirming what has been obvious for years: most of the human genome is junk. The term ‘dark DNA’ is laughable nonsense, dreamed up by people with a bad case of physics envy.
1. See pages 224-225 in my book and: On the importance of controls; The Random Genome Project.
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