Only 10-25% of Human Genome is Functional, New Estimate Says

In a paper published in the journal Genome Biology and Evolution, University of Houston Professor Dan Graur says that the functional portion of the human genome probably falls between 10% and 15%, with an upper limit of 25%. These figures are very different from one (about 80%) given in 2012 by the Encyclopedia of DNA Elements (ENCODE) project, but more optimistic than the 2014 estimate (8.2%) by Rands et al.

According to Professor Graur, the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower.

Professor Graur took a deceptively simple approach to determining how much of the genome is functional, using the deleterious mutation rate — that is, the rate at which harmful mutations occur — and the replacement fertility rate.

Both genome size and the rate of deleterious mutations in functional parts of the genome have previously been determined, and historical data documents human population levels.

With that information, the researcher developed a model to calculate the decrease in reproductive success induced by harmful mutations, known as the ‘mutational load,’ in relation to the portion of the genome that is functional.

The functional portion of the genome is described as that which has a selected-effect function, that is, a function that arose through and is maintained by natural selection.

Protein-coding genes, RNA-specifying genes and DNA receptors are examples of selected-effect functions.

In Professor Graur’s model, only functional portions of the genome can be damaged by deleterious mutations; mutations in nonfunctional portions are neutral since functionless parts can be neither damaged nor improved.

Because of deleterious mutations, each couple in each generation must produce slightly more children than two to maintain a constant population size.

“Over the past 200,000 years, replacement-level fertility rates have ranged from 2.1 to 3 children per couple; global population remained remarkably stable until the beginning of the 19th century, when decreased mortality in newborns resulted in fertility rates exceeding replacement levels,” Professor Graur said.

“If 80% of the genome were functional, unrealistically high birth rates would be required to sustain the population even if the deleterious mutation rate were at the low end of estimates.”

“For 80% of the human genome to be functional, each couple in the world would have to beget on average 15 children and all but two would have to die or fail to reproduce.”

“If we use the upper bound for the deleterious mutation rate (2×10⁸ mutations per nucleotide per generation), then the number of children that each couple would have to have to maintain a constant population size would exceed the number of stars in the visible Universe by ten orders of magnitude.”

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Dan Graur. An upper limit on the functional fraction of the human genome. Genome Biol Evol, published online July 11, 2017; doi: 10.1093/gbe/evx121