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Dan Graur, Anti-ENCODE Crusader, Is Back

Dan Graur

Headline in, of all places, the New York Post:

Human DNA is mostly trash, biologists say

At least 75 percent of our DNA is useless junk, according to a new study.

Researchers at the University of Houston calculated that only 10 to 15 percent of the human genome is functional, and definitely no more than 25 percent. That makes the remaining 75 to 90 percent of our genome “junk” — useless matter that isn’t toxic or harmful, it’s mostly just … there. The study was recently published in Genome Biology and Evolution.

Biologists have argued for years about whether or not our DNA is mostly trash or mostly purposeful. A study conducted in 2012 stated that up to 80 percent of our DNA plays some role in making us who we are — a claim that Dan Graur, lead author of the most recent study, hopes his findings will put to rest.

The study is covered in a range of more sedate venues, but when even the rabble-rousing tabloids pay attention, that’s a feather in the cap for anti-ENCODE, pro-Junk DNA crusader Dan Graur who is not seeking to convince fellow scientists alone. (See “Dan Graur, Darwin’s Reactionary.”)

New Scientist echoes:

At least 75 per cent of our DNA really is useless junk after all

You’re far from a perfect product. The code that makes us is at least 75 per cent rubbish, according to a study that suggests most of our DNA really is junk after all.

After 20 years of biologists arguing that most of the human genome must have some kind of function, the study calculated that in fact the vast majority of our DNA has to be useless. It came to this conclusion by calculating that, because of the way evolution works, we’d each have to have a million children, and almost all of them would need to die, if most of our DNA had a purpose.

From the paper itself:

Abstract:

For the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower.

That’s stated in more formal terms, but is there anything to it? In arguing for 75 percent of the human genome as trash, has Dr. Graur slain the ENCODE dragon and rescued the Junk DNA myth? Nah.

We read the paper, and looked over Graur’s accompanying PowerPoint. We’re not impressed by theoretical population genetics because it is based on neo-Darwinian assumptions rather than biological realities. Basically, he is using that circular science to add a quantitative gloss to his fundamental position, namely that if ENCODE is right then evolution is wrong, and evolution can’t be wrong, so ENCODE can’t be right.

Briefly, the major weakness of Graur’s models lies in the simplifying assumptions he makes. Graur presents only the stripped down version of the math behind his calculations, so until the book he references as a source arrives in our offices we can’t tell what assumptions are hidden behind that screen. But for sure there is the assumption of a constant population size.

There has been no constant population size or fertility rate over recorded human history, and likely before. One could argue that mutation rates have varied as well. To judge from the sources he cites on demography, Graur may be overly strict in his estimate of mean replacement fertility, and the average offspring per woman over the history of humankind. A mean replacement fertility of 3.5 per couple, given historical infant mortality, may be more appropriate.

A wild card, meanwhile, is the estimate of the percentage of mutations that are deleterious. The paper cited by Graur for the figure of 40 percent deleterious mutations was based on work on one protein in bacteria. Another paper studying human SNPs (mutations) found that only about one quarter were deleterious. These estimates are crude approximations and subject to error, as the range of values Graur quotes shows. Which number is chosen has a clear impact on the number calculated for the percentage of our genome that is functional.

These two numbers drive the train. If the mean replacement fertility value were higher, and the percent deleterious mutation value were lower, then the range of possible values for the percentage of our genome that is functional becomes higher.

It should be remembered that many once thought, as Richard Dawkins put it in 2009 in The Greatest Show on Earth, that “the greater part (95 per cent in the case of humans) of the genome might as well not be there, for all the difference it makes” (p. 333)! ENCODE determined a range of possible functional sequences of 20-80 percent. It would not be a surprise, given the above considerations, that the percentage of our genome that is functional may be double what Graur estimates. This places the percentage of junk DNA considerably lower than it was historically thought to be, and well within the range found by ENCODE.

In the end, though, it is empirical studies that will determine the actual percentage that is functional. We still bet on functionality.

Photo credit: Spencer Means, via Flickr.