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Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
[ENCODE apophenia or a panglossian analysis of the human genome]
Didier Casane1, Julien Fumey2, Patrick Laurenti1
1Laboratoire Évolution, génomes, comportement, écologie, CNRS université Paris-Sud UMR 9191, IRD UMR 247, Avenue de la Terrasse, bâtiment 13, boîte postale 1, 91198 Gif-sur-Yvette, France - Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.
Abstract:
In September 2012, a batch of more than 30 articles presenting the results of the ENCODE (Encyclopaedia of DNA Elements) project was released. Many of these articles appeared in Nature and Science, the two most prestigious interdisciplinary scientific journals. Since that time, hundreds of other articles dedicated to the further analyses of the Encode data have been published. The time of hundreds of scientists and hundreds of millions of dollars were not invested in vain since this project had led to an apparent paradigm shift: contrary to the classical view, 80% of the human genome is not junk DNA, but is functional. This hypothesis has been criticized by evolutionary biologists, sometimes eagerly, and detailed refutations have been published in specialized journals with impact factors far below those that published the main contribution of the Encode project to our understanding of genome architecture. In 2014, the Encode consortium released a new batch of articles that neither suggested that 80% of the genome is functional nor commented on the disappearance of their 2012 scientific breakthrough. Unfortunately, by that time many biologists had accepted the idea that 80% of the genome is functional, or at least, that this idea is a valid alternative to the long held evolutionary genetic view that it is not. In order to understand the dynamics of the genome, it is necessary to re-examine the basics of evolutionary genetics because, not only are they well established, they also will allow us to avoid the pitfall of a panglossian interpretation of Encode. Actually, the architecture of the genome and its dynamics are the product of trade-offs between various evolutionary forces, and many structural features are not related to functional properties. In other words, evolution does not produce the best of all worlds, not even the best of all possible worlds, but only one possible world.
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