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J Theor Biol. 2018 Feb 7;438:143-150. doi: 10.1016/j.jtbi.2017.11.015. Epub 2017 Nov 23.

Temporal ordering of substitutions in RNA evolution: Uncovering the structural evolution of the Human Accelerated Region 1.

Author information

1
TFome Research Group, Bioinformatics Group, Interdisciplinary Center of Bioinformatics, Department of Computer Science, University of Leipzig, Härtelstrasse 16-18, Leipzig, D-04107, Germany; Paul-Flechsig-Institute for Brain Research, University of Leipzig, Jahnallee 59, Leipzig, D-04109, Germany; Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, 04107, Germany. Electronic address: bia@bioinf.uni-leipzig.de.
2
Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, 04107, Germany. Electronic address: choener@bioinf.uni-leipzig.de.
3
National Research Council Canada, Information and Communication Technologies, 100 des Aboiteaux Street, Suite 1100, NB E1A7R1, Moncton, Canada. Electronic address: dan.tulpan@nrc-cnrc.gc.ca.
4
Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, 04107, Germany; University of Vienna, Institute for Theoretical Chemistry, Vienna A-1090, Austria; Max Planck Institute for Mathematics in the Science, Leipzig, 04103, Germany; Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, 04103, Germany; Santa Fe Institute, Santa Fe, NM, 87501, USA. Electronic address: studla@bioinf.uni-leipzig.de.
5
TFome Research Group, Bioinformatics Group, Interdisciplinary Center of Bioinformatics, Department of Computer Science, University of Leipzig, Härtelstrasse 16-18, Leipzig, D-04107, Germany; Paul-Flechsig-Institute for Brain Research, University of Leipzig, Jahnallee 59, Leipzig, D-04109, Germany; Bioinformatics Group, Department of Computer Science and Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, 04107, Germany; Bioinformatics, Faculty of Agricultural Sciences, Institute of Animal Science, University of Hohenheim, Garbenstrasse 13, Stuttgart, 70593, Germany; Freie Universität Berlin, Faculty for Biology, Chemistry, and Pharmacy, Institute for Biology, Königin-Luise-Strasse 1-3, Berlin, 14195, Germany. Electronic address: katja.nowick@fu-berlin.de.

Abstract

The Human Accelerated Region 1 (HAR1) is the most rapidly evolving region in the human genome. It is part of two overlapping long non-coding RNAs, has a length of only 118 nucleotides and features 18 human specific changes compared to an ancestral sequence that is extremely well conserved across non-human primates. The human HAR1 forms a stable secondary structure that is strikingly different from the one in chimpanzee as well as other closely related species, again emphasizing its human-specific evolutionary history. This suggests that positive selection has acted to stabilize human-specific features in the ensemble of HAR1 secondary structures. To investigate the evolutionary history of the human HAR1 structure, we developed a computational model that evaluates the relative likelihood of evolutionary trajectories as a probabilistic version of a Hamiltonian path problem. The model predicts that the most likely last step in turning the ancestral primate HAR1 into the human HAR1 was exactly the substitution that distinguishes the modern human HAR1 sequence from that of Denisovan, an archaic human, providing independent support for our model. The MutationOrder software is available for download and can be applied to other instances of RNA structure evolution.

KEYWORDS:

Computational modeling; Data visualisation; Dynamic programming; Human evolution; Non-coding RNA; Secondary structure

PMID:
29175608
DOI:
10.1016/j.jtbi.2017.11.015
[Indexed for MEDLINE]
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