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The extent of functionality in the human genome

Recently articles have been published disputing the main finding of the ENCODE project that the majority of the human genome exhibits biochemical indices of function, based primarily on low sequence conservation and the existence of larger genomes in some ostensibly simpler organisms (the C-value en...

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Autores principales: Mattick, John S, Dinger, Marcel E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685169/
http://dx.doi.org/10.1186/1877-6566-7-2
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author Mattick, John S
Dinger, Marcel E
author_facet Mattick, John S
Dinger, Marcel E
author_sort Mattick, John S
collection PubMed
description Recently articles have been published disputing the main finding of the ENCODE project that the majority of the human genome exhibits biochemical indices of function, based primarily on low sequence conservation and the existence of larger genomes in some ostensibly simpler organisms (the C-value enigma), indicating the likely presence of significant amounts of junk. Here we challenge these arguments, showing that conservation is a relative measure based on circular assumptions of the non-functionality of transposon-derived sequences and uncertain comparison sets, and that regulatory sequence evolution is subject to different and much more plastic structure-function constraints than protein-coding sequences, as well as positive selection for adaptive radiation. We also show that polyploidy accounts for the higher than expected genome sizes in some eukaryotes, compounded by variable levels of repetitive sequences of unknown significance. We argue that the extent of precise dynamic and differential cell- and tissue-specific transcription and splicing observed from the majority of the human genome is a more reliable indicator of genetic function than conservation, although the unexpectedly large amount of regulatory RNA presents a conceptual challenge to the traditional protein-centric view of human genetic programming. Finally, we suggest that resistance to these findings is further motivated in some quarters by the use of the dubious concept of junk DNA as evidence against intelligent design.
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spelling pubmed-46851692015-12-22 The extent of functionality in the human genome Mattick, John S Dinger, Marcel E Hugo J Review Recently articles have been published disputing the main finding of the ENCODE project that the majority of the human genome exhibits biochemical indices of function, based primarily on low sequence conservation and the existence of larger genomes in some ostensibly simpler organisms (the C-value enigma), indicating the likely presence of significant amounts of junk. Here we challenge these arguments, showing that conservation is a relative measure based on circular assumptions of the non-functionality of transposon-derived sequences and uncertain comparison sets, and that regulatory sequence evolution is subject to different and much more plastic structure-function constraints than protein-coding sequences, as well as positive selection for adaptive radiation. We also show that polyploidy accounts for the higher than expected genome sizes in some eukaryotes, compounded by variable levels of repetitive sequences of unknown significance. We argue that the extent of precise dynamic and differential cell- and tissue-specific transcription and splicing observed from the majority of the human genome is a more reliable indicator of genetic function than conservation, although the unexpectedly large amount of regulatory RNA presents a conceptual challenge to the traditional protein-centric view of human genetic programming. Finally, we suggest that resistance to these findings is further motivated in some quarters by the use of the dubious concept of junk DNA as evidence against intelligent design. Springer Berlin Heidelberg 2013-07-15 2013-12 /pmc/articles/PMC4685169/ http://dx.doi.org/10.1186/1877-6566-7-2 Text en © Mattick and Dinger; licensee Springer. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Mattick, John S
Dinger, Marcel E
The extent of functionality in the human genome
title The extent of functionality in the human genome
title_full The extent of functionality in the human genome
title_fullStr The extent of functionality in the human genome
title_full_unstemmed The extent of functionality in the human genome
title_short The extent of functionality in the human genome
title_sort extent of functionality in the human genome
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685169/
http://dx.doi.org/10.1186/1877-6566-7-2
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