Researchers look into percentage of human genome that is functional, question the 80% suggested by the ENCODE Project

A paper published in Genome Biology and Evolution explored the 2013 ENCODE Project’s assertion that 80 percent of the Human genome is functional.

According to the paper, critics of ENCODE argued that the amount of DNA in our cells that can be functional is limited by the “mutational load,” the amount of deleterious mutations that can be tolerated in the genome because much of our genome is “junk.” Instead, the authors propose that a mutational load argument is unlikely to set a lower limit on the proportion of the genome that is functional.

Benjamin Galeota-Sprung, Paul Sniegowski, and Warren Ewens, of the University of Pennsylvania Department of Biology dove into the research, looking to learn more about how much of the human genome, which is comprised of more than three billion base pairs, is actually functional.

“We stress that we, in this work, take no position on the actual proportion of the human genome that is likely to be functional,” explained the authors. 

They acknowledge the C-value paradox, which states that genome size does not necessarily correlate to the complexity of the genome. They also noted that between 3 percent and 15 percent of the human genome is subject to purifying selection, which accounts for rapidly evolving but constrained sequences.

Galeota-Sprung, Sniegowski, and Ewens suggest that the high fraction of functionality (80 percent) suggested by the ENCODE project is difficult to bring to terms with the knowledge that a large portion of the genome has inactivated transposable elements. Also, using an estimate as high as 80 percent does not resolve the C-value paradox, so that 80 percent estimate may not be accurate, nor helpful.

But they argued that critics of that 80% value make false assumptions in their arguments. ENCODE-critics assume that we can measure the fitness of a human being “with zero deleterious mutations,” but the authors argue that this not meaningful because “in a finite population of realistic size, such a person will never exist.”

Because an individual with zero deleterious mutations, the fitness level used in the ENCODE project, is unlikely to exist, Galeota-Sprung, Sniegowski, and Ewens say that calculations on a mutational load should use a more likely level of fitness that is likely to exist in a real population.

This research was funded by a National Aeronautics and Space Administration grant to PDS.