Getting “function” right

Addressing critiques (1, 2) of the Encyclopedia of DNA Elements’ (ENCODE) claims to have dispelled the notion of “junk DNA,” Kellis et al. (3) “review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments.” The authors consider that “both scientists and nonscientists have an intuitive definition of function, but each scientific discipline relies primarily on different lines of evidence indicative of function” (3). In fact, biologists differ among themselves (and from the laity) in underlying concepts of “function,” as well as in what they consider to be evidential support for it (4).

Surprisingly, nowhere do Kellis et al. (3) mention the “causal role” vs. “selected effect” conceptual distinction refined over the last several decades by philosophers of science (4). Distinguishing what an element (genetic or otherwise) does (its causal role) from why it exists (its selected effect) is at the heart of biology. Glossing over this distinction, as Kellis et al. do (3), would be justified only if we had reason to believe that natural selection is “so powerful and the constraints upon it so few that direct production of adaptation though its operation becomes the primary cause of nearly all organic form, function and behavior” (5).

Kellis et al. (3) do admit that some evidences of function (low-level noncoding RNA transcription, for example) may in fact “simply be biological noise of various kinds” and that “biochemical approaches” are more noise-prone than are “evolutionary” (conservation-based) approaches. So beneath it all these authors may well appreciate that “function” entails natural selection. However, clearly they see the take-home message from ENCODE to be that there is much more function than believed by adherents of the “junk DNA” notion, and apparently Kellis et al. consider arguments based on C-value (“Why do lungfishes have 40 times as much DNA as us?”) only marginally relevant. The authors do not rise to the challenge of predicting how many functional elements such bloated genomes might boast.

Without a more nuanced understanding, researchers using different “approaches” will be left attempting to resolve conceptual disputes on experimental and technical grounds. This plainly cannot work. If some believe that selected-effect function can be established simply by developing better methods for elucidating causal roles, and others hold that only “in the light of evolution” does biology make sense, no amount of any kind of data will resolve their disagreement.

When selection is reasonably invoked, the level at which it is exerted and the entities whose interests it serves—for whom it is a “function”—also matter. Kellis et al. (3) recognize that a large fraction of “biochemical signatures” emerges from intragenomically selected “selfish” entities, primarily retroposons. Some are coopted into regulatory roles, but do the majority of such elements actually serve our interests?

Such arguments are semantic, but not merely so. Research funding in genomics depends to a considerable extent on the belief that what we are looking at is not junk or selfish genetic parasites, although one argument leveled by evolutionists against creationists hinges on the claim that it is. Words and concepts drive research and its interpretation.