The Case for Junk DNA

The search for function in the genome It has been known for several decades that only a small fraction of the human genome is made up of protein-coding sequences and that at least some noncoding DNA has important biological functions. In addition to coding exons, the genome contains sequences that are transcribed into functional RNA molecules (e.g., tRNA, rRNA, and snRNA), regulatory regions that control gene expression (e.g., promoters, silencers, and enhancers), origins of replication, and repeats that play structural roles at the chromosomal level (e.g., telomeres and centromeres). New discoveries regarding potentially important sequences amongst the nonprotein-coding majority of the genome are becoming more prevalent. By far the best-known effort to identify functional regions in the human genome is the recently completed Encyclopaedia of DNA Elements (ENCODE) project [1], whose authors made the remarkable claim that a “biochemical function” could be assigned to 80% of the human genome [2]. Reports that ENCODE had refuted the existence of large amounts of junk DNA in the human genome received considerable media attention [3], [4]. Criticisms that these claims were based on an extremely loose definition of “function” soon followed [5]–[8] (for a discussion of the relevant function concepts, see [9]), and debate continues regarding the most appropriate interpretation of the ENCODE results. Nevertheless, the excitement and subsequent backlash served to illustrate the widespread interest among scientists and nonspecialists in determining how much of the human genome is functionally significant at the organism level.