In the fall of 2012, the ENCODE Project reported that at least 80 percent of the human genome consists of functional sequences. A number of scientists have criticized the ENCODE conclusions, yet there are some scientists, such as molecular geneticist John Mattick, who accept and defend them.
In September 2012, the ENCODE Project Consortium announced the results of the second phase of research designed to identify and catalog all the functional elements in the human genome.1 I reported on this announcement in the September 6, 2012episode of RTB’s Science News Flash podcast, and suggested that the ENCODE results may well be one of the most important scientific achievements in my lifetime, or at least in my time as a professional biochemist.
Since the initial sequencing of the human genome, many skeptics and evolutionary biologists have asserted that the most compelling evidence for human evolution—and the most potent challenge against intelligent design/creationism—is the vast amount of junk DNA in the human genome. And yet, with the results of the ENCODE Project, these arguments evaporate. We can no longer consider the human genome a vast wasteland of junk, but an elegant system that displays sophistication in its architecture and operation, far beyond what most evolutionary biologists ever imagined.
When announced, the ENCODE results generated quite a bit of Internet chatter. Many skeptics asserted that the media and design proponents overhyped and misconstrued the project’s discoveries. Shortly thereafter, several papers appeared in the scientific literature highlighting ENCODE’s “flaws.”2 Many evolutionary biologists hope these critiques will undermine the project’s conclusion that 80 percent of the human genome, at minimum, contains functional DNA elements.
Yet, very good reasons exist for thinking that the ENCODE Project’s results are still valid. In fact, I have written several articles that provide a detailed response to each criticism. I conclude that the charges against ENCODE lack technical merit and appear to be motivated by philosophical considerations more than anything else. To read my response to these criticisms click on the below links:
It is interesting to note that not everyone in the scientific community agrees with the ENCODE skeptics. Molecular geneticist John Mattick, executive director of the Garvan Institute of Medical Research in Australia, believes in ENCODE’s validity.3 In a recent article, Mattick and his coauthor, Marcel Dinger, argue, like me, that the criticisms of ENCODE are unwarranted technically and are motivated by non-scientific considerations.
One of the chief criticisms leveled at ENCODE relates to its use of a causal definition of function to determine functionality within the human genome. That is, a sequence element in the genome possesses function if it performs an observationally or experimentally identified role. ENCODE skeptics argue that this definition is faulty; instead, the project should have relied on sequence conservation (the so-called selected effect definition) as a way to measure function.
According to the selected effect definition, sequences in genomes can be deemed functional only if they evolved under evolutionary processes to perform a particular function. Once these sequences are evolved, the effects of natural selection make them resistant to change because, at this point, any further alteration would compromise the function of the sequence and, consequently, be deleterious. Reduced survivability and reproductive success would then eliminate organisms possessing deleterious sequence variations from the population. Hence, functional sequences are those under the effects of selection. And based on a selected effect definition of function, only 10 percent (not 80) of the human genome could be considered functional.
Mattick and Dinger decry the weakness of the selected effect definition. They argue that the genome’s regulatory regions are much more malleable than the selected effect idea suggests, retaining function in the face of mutational changes. Thus, sequence conservation (one way to detect selection at work) cannot be a valid marker of function. Mattick and Dinger propose and defend differential transcription, an alternative measure of function. They note that during the course of development, the vast majority of the human genome (and the genome of other mammals) is “differentially transcribed in precise cell-specific patterns” to generate RNA molecules with a regulatory role. It is interesting to note that this is a causal definition of function, meaning it relies on cause-and-effect relationships.
In response to Mattick and Dinger’s definition of function, ENCODE skeptics claim that transcription of the genome is noisy (random, and arbitrary). As such, transcription cannot be viewed as an indicator of function. In a previous article, I offer a response to this challenge. So, too, do Mattick and Dinger. They state: