The Junk DNA Wars

This month, the New York Times' published a report on “the junk DNA wars” asking “Is Most of Our DNA Garbage”? 1/ Readers of the article (and an anonymous follow-up piece on the reactions appearing in science blogs) 2/ would come away thinking that there is a serious debate in the scientific community over the proposition that “junk DNA” is “mostly functional.”

Without defining terms like “functional” and “junk,” however, it is impossible to know what is in dispute and what is not.The follow-up piece is particularly frustrating. It observes that

Some scientists, like T. Ryan Gregory, a evolutionary biologist ... argue that if DNA is mostly functional, then it’s hard to explain why rather humble species, like the onion, have far more DNA than we do. ...

Those who disputed Gregory’s findings [sic — Gregory did not discover the long-standing C-value paradox 3/ ], including supporters of intelligent design, cited the Encode Project, an N.I.H.-sponsored attempt to catalog the functional elements of the genome. Encode scientists found that 80 percent of the genome had “biochemical functions,” suggesting that there was a lot less junk DNA than scientists had thought. But did “biochemical function” really mean anything?

For many scientists, it didn’t. A University of Toronto biochemist, Larry Moran, wrote that “the general public has been snowed by the Encode publicity campaign and by naïve journalists who have enthusiastically reported that junk DNA is dead.”

But the Times' writers did not explain why “many scientists” are not snowed by the 80% statistic. After reading some of the ENCODE papers and the surrounding (typically hyperbolic) publicity, I concluded that:

The ENCODE papers show that 80% of the genome displays signs of certain types of biochemical activity—even though the activity may be insignificant, pointless, or unnecessary. This 80% includes all of the introns, for they are active in the production of pre-mRNA transcripts. But this hardly means that they are regulatory or otherwise functional. Indeed, if one carries the ENCODE definition to its logical extreme, 100% of the genome is functional—for all of it participates in at least one biochemical process—DNA replication.

That the ENCODE project would not adopt the most extreme biochemical definition is understandable—that definition would be useless. But the ENCODE definition is still grossly overinclusive from the standpoint of evolutionary biology. From that perspective, most estimates of the proportion of “functional” DNA are well under 80%. 4/

In short, evolutionary biologists reject "biochemical function" as a criterion for recognizing "junk" because not every bit of biochemical activity affects the reproductive fitness of organisms. (Neither does chemical activity per se show any influence on phenotypes that are related to the healthy functioning of those organisms.) To the evolutionary biologists, the term “junk DNA” means parts of the genome in which the particular DNA sequences (the order of the base pairs) do not have evolutionary significance. The Times article defines “junk DNA” differently, and vaguely, as “pieces of DNA that do nothing for us.” This is not the scientific definition. In fact, the earliest papers on “junk DNA” proposed that much of it might “do something” for us.

The “junk DNA war” (or rather the confusion about the meaning of the term “junk”) has spilled over into the legal realm. A brief that leading genetics and genomics researchers submitted to the U.S. Supreme Court to clarify the privacy implications of forensic DNA typing tried to address it. 5/ These researchers observed that

• In genetics, “junk DNA” denotes sequences that lie outside of genes and that are not under detectable selective pressure: that such DNA exists is not in doubt.
• “Junk” DNA sequences could be biologically useful or interesting yet not be useful for disease diagnosis or prediction.
• ENCODE data do not reveal that anywhere near 80% of the genome contains medically relevant information.
• The ENCODE findings indicate that the system that regulates gene expression is exquisitely complex, but they do little to change the status of “junk DNA” in general.

As far as I know, these conclusions have not been contradicted by new studies, but I have not conducted a recent literature review and would be grateful to hear of relevant papers that undermine these observations.

Notes

1. Carl Zimmer, Is Most of Our DNA Garbage?, N.Y. Times Mag., Mar. 5, 2015 
2. Re: Is Most of Our DNA Garbage?, N.Y. Times Sunday Mag., Mar. 20, 2015
3. See Sean R. Eddy, The C-value Paradox, Junk DNA and ENCODE, 22 Current Biology R898 (2012)
4. David H. Kaye, ENCODE’S “Functional Elements” and the CODIS Loci (Part II. Alice in Genomeland), Forensic Science, Statistics, and the Law, Sept. 18, 2012 (note omitted)
5. Brief of Genetics, Genomics, and Forensic Science Researchers as Amici Curiae in Support of Neither Party, Maryland v. King, No. 12-204, Dec, 28, 2012, reprinted in part in Henry T. Greely & David H. Kaye, A Brief of Genetics, Genomics and Forensic Science Researchers in Maryland v. King, 53 Jurimetrics J. 43 (2013), available at http://ssrn.com/abstract=2403063http://ssrn.com/abstract=2403063. Disclosure statement: I prepared an initial draft of the brief and coordinated the revisions to it.