The C value paradox, as initially coined, was encountered in early eukaryotic genomic
studies with the oddity that genome size was not necessarily correlated with organism
complexity . With the discovery of non-coding DNA in the 1970s, it became apparent that the size
of the eukaryotic genome was not related to the number of genes contained within it.
Indeed, only a small portion (approximately 2%) of the human genome carries coding
genes [2-4], the rest being the so-called “junk DNA” . The human genome project further elucidated the number of genes in our genomes -
counting a paltry 20,000 to 25,000 genes [2-4]. With so few genes one might ask “how could such a complex organism as Homo sapiens pass on the necessary genetic blueprint to the next generation?” An equally enticing
question could be “how could nature be so wasteful and commit so much junk DNA to
the human genome?” The
lements (ENCODE) project has shed some light on these two questions. There is not
one paper to cite but greater than 30 studies  that were coordinated and published in concert describing the results of a multi-year
consortium effort to catalogue the functional elements of human DNA. Hundreds of authors
reported on analyses of thousands of data sets. A good summary of the work is captured
in the ENCODE Project Consortium’s September 2012 publication titled “An integrated
encyclopedia of DNA elements in the human genome” . The ENCODE project identified a large number of functional elements, defined as
sites that encoded a product or exhibited a biochemical signature in the human genome.
The power of current DNA sequencing technologies made the Consortium project possible.
The depth of analysis is impressive. In this one paper more than 1,600 data sets were
analyzed for a multitude of elements including human protein-coding and non-coding
RNAs, pseudogenes, RNA from different cell lines, binding locations of a number of
DNA-binding proteins and RNA polymerase components, DNase I hypersensitive sites,
locations for histone modifications, and DNA methylation. The most exciting finding
and one that may begin to address the two questions posed above was that 80.4% of
the genome has a biochemical function, that is, it is covered by or near at least
one ENCODE-identified element. More precisely, a large portion of the human genome
contains a regulatory event. The authors state that “95% of the genome lies within
8 kilobases (kb) of a DNA–protein interaction…, and 99% is within 1.7 kb of at least
one of the biochemical events measured by ENCODE.” The outcome is that the noncoding
junk DNA is far from being useless genome filler. Instead, seemingly inert DNA can
influence functional genes. The nature of genetic and epigenetic control is quite
complex and exquisite and today all that more appreciated. ENCODE is a public resource
that will contribute substantially to the understanding of gene expression and mechanisms
of disease and, hopefully, cures.