Conceptual and empirical challenges of ascribing functions to transposable elements.

ABSTRACT

Media attention and the subsequent scientific backlash engendered by the claim by spokespeople for the Encyclopedia of DNA Elements (ENCODE) project that 80% of the human genome has a biochemical function highlight the need for a clearer understanding of function concepts in biology. This article provides an overview of two major function concepts that have been developed in the philosophy of science--the causal role concept and the selected effects concept--and their relevance to ENCODE. Unlike in some previous critiques, the ENCODE project is not considered problematic here because it employed a causal role definition of function (which is relatively common in genetics) but because of how this concept was misused. In addition, several unique challenges that arise when dealing with transposable elements (TEs) but that were ignored by ENCODE are highlighted. These include issues surrounding TE-level versus organism-level selection, the origins versus the persistence of elements, and accidental versus functional organism-level benefits. Finally, some key questions are presented that should be addressed in any study aiming to ascribe functions to major portions of large eukaryotic genomes, the majorities of which are made up of transposable elements.