When the human genome was more or less fully described in 2003, only about 20,000 genes were identified and these functional genes seemed to occupy only about 1% of the three billion nucleotides. So, what was the rest of the material in the genome doing? Many scientists declared that the rest was ‘junk DNA’, discarded during the long process of trial and error in evolution. Others cautioned that at least some of the non-protein-coding DNA must have a purpose. Thus, an international consortium of scientists from 10 countries began a systematic survey of 1% of the human genome. The results of that survey (published in Nature June 14, 2007), revealed that most of the DNA seemed to have a function, or at least it was copied into other molecules in the cell. This was so surprising to the team that they decided to extend the project to cover the entire human genome.

In 2012 a new larger consortium published its results in a series of 30 articles. [Nature 489: 57-74.] The team found that: “The vast desert regions have now been populated with hundreds of thousands of features that contribute to gene regulation. And every cell type uses different combinations and permutations of these features to generate its unique biology. This richness helps to explain how relatively few protein-coding genes can provide the biological complexity necessary to grow and run a human being.” [Nature September 6, 2012 p. 47].

One evolutionary expectation that was not confirmed was that molecules with important functions would be “conserved” from ancestral populations. Instead, there were a lot of important molecules that are unique to humans. Thus, the consortium declared that “although many geneticists had thought that the functional elements would be those most conserved across species, they actually found that many important regulatory sequences have evolved rapidly.”  [p. 47] [In other words, there was no hint of non-human ancestors with similar features located in the human genome, so these features must have appeared very suddenly in humans.]

The most remarkable statement from the consortium was that 80% of the genome demonstrated some level of biochemical function. “Why evolution would maintain large amounts of ‘useless’ DNA had remained a mystery, and seemed wasteful. It turns out, however, that there are good reasons to keep this DNA.” [p. 54] So the good news was that the ‘deserts’ in the DNA were not junk after all. Another conclusion was that the regulatory system of gene expression in humans is vastly more complicated than we ever imagined.

At least three different levels of control in the expression of the DNA system have been discovered. The first is the nucleotides in the protein coding section of the DNA, but the control mechanisms are not straightforward.  It is now evident that a length of DNA (formerly called a gene) may contain fragments of information that can be stitched together in different combinations to produce all sorts of different proteins (see alternative splicing.)   The next layer are the “promoters” and “enhancers” which affect gene expression. The third level is the looping back of the DNA so that remote regions can be accessed to manage gene expression.

Two very significant findings from ENCODE II were that there is a high proportion of functionality throughout the genome and that the location of most disease associated markers are in the non-coding parts of the genome. These two findings were also major themes of ENCODE III, the results of which were published eight years after the ENCODE II reports were released. [Nature 583 #7818 pp. 699-710]. Thus, one paper in the same issue reported: “GWAS and cancer genomics studies continue to deposit-disease related sequence variations into public databases, and most of these variants fall into non-coding regions.” [p. 743]

The disease connection ties in with the question of functionality, since non-coding sequences were initially claimed to be nonfunctional and thus ‘junk DNA’. The ENCODE III team continued to defend the view from their previous reports that any nucleotide sequence that leads to a molecular product or to any chemical activity, is functional. Indeed, the ENCODE III team extended the identification of functional elements much further than ENCODE II. Thus, their summary statement was: “It has become apparent that, by virtually any metric, elements that govern transcription, chromatin organization, splicing, and other key aspects of genome control and function are densely encoded in many parts of the human genome sequence.” [p. 709]

The most amazing aspect of the ENCODE reports is the complexity of the DNA system and the fact that this project showed the concept of ‘junk DNA’ to be false. These features, as well as the massive information content of the DNA code, all testify to the intelligent design of the human genome.

Related Resources

• Diamond Jubilee for DNA Molecule ENCODE project