The C-value paradox, junk DNA and ENCODE

What is the C‐value paradox? You might expect more complex organisms to have progressively larger genomes, but eukaryotic genome size fails to correlate well with apparent complexity, and instead varies wildly over more than a 100,000-fold range. Single-celled amoebae have some of the largest genomes, up to 100-fold larger than the human genome. This variation suggested that genomes can contain a substantial fraction of DNA other than for genes and their regulatory sequences. C.A. Thomas Jr dubbed it the ‘C-value paradox’ in 1971. The C-value paradox is related to another puzzling observation, called ‘mutational load’: the human genome seems too large, given the observed human mutation rate. If the entire human genome were functional (in the sense of being under selective pressure), we would have too many deleterious mutations per generation. By 1970, rough calculations had suggested to several authors that maybe only 1–20% of the human genome could be genic, with the rest evolving neutrally or nearly so.