When the completion of the Human Genome Project was announced in 2001, scientists, the media, and the president considered it a breakthrough that promised to lead to cures for many diseases. As it turns out, the Human Genome Project was more like a parts list for a Boeing 777: the fact that we had the parts did not mean we knew how they fit together.[1]
A follow-up study was needed to determine what these parts do and how they relate to each other. This study took the form of the Encyclopedia of DNA Elements Project, or ENCODE. A recent Nature article discussing the completion and findings of ENCODE summarizes the status of genome research following the project: “First they sequenced it. Now they have surveyed its hinterlands. But no one knows how much more information the human genome holds, or when to stop looking for it.”[2]
ENCODE began in 2003 with the mission to “catalogue the ‘functional’ DNA sequences that lurk there [in the genome’s non-coding regions], learn when and in which cells they are active and trace their effects on how the genome is packaged, regulated and read.”[3] The project is a collaborative effort of over 32 laboratories in various countries. Its early phase, from 2003-2007, looked at the coding regions of DNA.[4] In 2007 scientists began looking at the non-coding regions, which do not directly code for amino acids. Their findings are published in 30 papers documenting functionality in the non-coding regions of DNA.[5]
Prior to ENCODE, scientists were able to identify about 1% - 2% of the genome as coding for the construction of proteins; however, they were unable to account for the rest of it. What they found was that the human genome is anything but a simple, linear model of progression through a DNA-to-RNA-to- amino acids-to-proteins process. It is certainly more than a repository of evolutionary relics no longer needed by the body, as some contended. Within the regions of the genome that had been labeled “junk” or “noncoding” or “retroviruses” lies another layer of complexity signaling for epigenetic factors.
Scientists have known for some time of the existence of epigenetic factors—parts of the genome that affect gene expression and regulation, but are not part of the genetic sequence of A, T, G, or C. What is surprising is the extent to which the non-coding region of DNA has now, in light of the findings of ENCODE, been implicated in these factors.
Two key epigenetic factors are methylation and histone packing. Methyl is a chemical group (CH3 -) that attaches to DNA nucleotides. These methyl groups serve as “flags” signaling when genes should be turned on or off or when regulator proteins need to be recruited. While every cell within an organism may have the same genetic sequence, each of these cells usually has a unique methyl landscape. A histone is a wound up ball of DNA that packs the DNA in such a way that the entire sequence is able to fit within the nucleus of a cell. It turns out that the three-dimensional orientation of the histone packing helps activate or de-activate certain regions of DNA.
These findings have several implications for bioethics. On a practical level, the epigenetic factors, particularly methylation, are some of the key players in converting induced pluripotent stem cells into certain cell types. Apparently, the methylation landscape serves as a signal that tells the cell its future identity. Furthermore, problems in the methylation landscape have been shown to cause some diseases, including certain cancers. On a philosophical level, these findings call into question the reductionistic assumptions endemic in science and medicine. The genome is much more complex than was once thought. The idea that “one gene codes for one trait” has been laid to rest. While there are a few cases of single genes that code for certain diseases (such as Huntington’s Disease), this is the exception, not the rule. In other words, the GATTACA-like scenario of building a “standard option” embryo with “selective upgrades” has become an outdated notion based on a simplistic view of the genome.
[1] Cf. Nova, “Cracking the Code of Life,” http://www.pbs.org/wgbh/nova/body/cracking-the-code-of-life.html (accessed October 12, 2012).
[2] Brenden Maher, “ENCODE: The Human Encyclopaedia,” Nature 489, no. 7414 (September 5, 2012), http://www.nature.com/news/encode-the-human-encyclopaedia-1.11312 (accessed October 12, 2012).
[3] Ibid.
[4] The ENCODE Project Consortium, “Identification and Analysis of Functional Elements in 1% of the Human Genome by the ENCODE Pilot Project,” Nature 447, no. 7146 (June 14, 2007), http://www.nature.com/nature/journal/v447/n7146/full/nature05874.html (accessed October 12, 2012).
[5] The ENCODE Project Consortium, “An Integrated Encyclopedia of DNA Elements in the Human Genome,” Nature 489, no. 7414 (September 6, 2012), http://www.nature.com/nature/journal/v489/n7414/full/nature11247.html (accessed October 12, 2012).
Heather Zeiger, "Revisiting ‘Junk DNA’: Epigenetics and Encode,” Dignitas 19, no. 3 (2012): 1.
