The Human Genome Project was anticipated to have provided us with a blueprint of what makes us human. Very quickly, it became apparent that the published genome was not a blueprint: we had raw data but no information. Although a watershed, it was but a first step in understanding the genetics of human beings.
The follow-on ENCODE Project Consortium focused on a selected 1% of the human genome "to map a variety of sequence elements including genes, promoters, enhancers, repressor or silencer sequences, exons, replication origin and termination sites, transcription factor binding sites, methylation sites, DNase I hypersensitive sites, chromatin modifications, conserved sequences, and RNA transcripts, to name only those considered in the pilot project." One of the major conclusions concerns the organisation of functional elements in the genome. In some cases, this confirmed current models but, the authors of the Nature paper write, "we also uncovered some surprises that challenge the current dogma on biological mechanisms." The surprises all involve unexpected complexity in the genome; complexity that necessitates a revision of the way we think about transcription and genes.
Furthermore, the ENCODE findings should lead to the final demise of the term "Junk DNA". "The ENCODE consortium's major findings include the discovery that the majority of DNA in the human genome is transcribed into functional molecules, called RNA, and that these transcripts extensively overlap one another. This broad pattern of transcription challenges the long-standing view that the human genome consists of a relatively small set of discrete genes, along with a vast amount of so-called junk DNA that is not biologically active." The majority of the genome now appears to have functionality. It must be regarded as a "complex, interwoven network" with genes being just one of many functional elements.
It is worth reminding ourselves that the "long-standing view" of the human genome has been used to argue against Intelligent Design. Evolutionary biologists have regarded the existence of Junk DNA as evidence supporting their Darwinian perspective (having a pool of non-functional genetic material with the potential to mutate into something biologically meaningful). Not only has the supposed reservoir of variability evaporated (by the discovery of functionality for most of the genome), the organisational structure of the functional elements has been found to be breathtakingly complex. No wonder the evolutionary biologists find it difficult to avoid using the word "surprise"! ID biologists, on the other hand, have received the findings with enthusiasm, because the discovery of functionality and extraordinary complexity fits the expectation of design-oriented thinking.
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
The ENCODE Project Consortium
Nature, 447, (14 June 2007), 799-816 | doi:10.1038/nature05874 [Open Access]
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
National Human Genome Research Institute (Press Release), New Findings Challenge Established Views on Human Genome, June 13 2007.
Weinstock, G.M., ENCODE: More genomic empowerment, Genome Research, 2007 17: 667-668. [Open Access]
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