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Using Non-Reversible Context-Dependent Evolutionary Models to Study Substitution Patterns in Primate Non-Coding Sequences

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Abstract

We discuss the importance of non-reversible evolutionary models when analyzing context-dependence. Given the inherent non-reversible nature of the well-known CpG-methylation-deamination process in mammalian evolution, non-reversible context-dependent evolutionary models may be well able to accurately model such a process. In particular, the lack of constraints on non-reversible substitution models might allow for more accurate estimation of context-dependent substitution parameters. To demonstrate this, we have developed different time-homogeneous context-dependent evolutionary models to analyze a large genomic dataset of primate ancestral repeats based on existing independent evolutionary models. We have calculated the difference in model fit for each of these models using Bayes Factors obtained via thermodynamic integration. We find that non-reversible context-dependent models can drastically increase model fit when compared to independent models and this on two primate non-coding datasets. Further, we show that further improvements are possible by clustering similar parameters across contexts.

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Abbreviations

GTR:

General time-reversible

BF:

Bayes Factor

QE:

Quasistatic estimate

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Acknowledgments

Computational resources and services used in this study were provided by Ghent University. We would like to thank Stijn De Weirdt in particular for his assistance in using Ghent University’s High Performance Computing facility. We would also like to thank Hervé Philippe and one anonymous referee for providing useful comments on a first version. Yves Van de Peer acknowledges support from an Interuniversity Attraction Pole (IUAP) grant for the BioMaGNet project (Bioinformatics and Modelling: from Genomes to Networks, ref. p6/25). Stijn Vansteelandt acknowledges support from IAP research network Grant No. P06/03 from the Belgian government (Belgian Science Policy). We acknowledge the support of Ghent University (Multidisciplinary Research Partnership “Bioinformatics: from nucleotides to networks”).

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Authors and Affiliations

  1. Department of Plant Systems Biology, VIB, Ghent University, Technologiepark 927, 9052, Ghent, Belgium

    Guy Baele & Yves Van de Peer

  2. Bioinformatics and Evolutionary Genomics, Department of Molecular Genetics, Ghent University, 9052, Ghent, Belgium

    Guy Baele & Yves Van de Peer

  3. Department of Applied Mathematics and Computer Science, Ghent University, Krijgslaan 281 S9, 9000, Ghent, Belgium

    Stijn Vansteelandt

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  1. Guy Baele
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  2. Yves Van de Peer
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  3. Stijn Vansteelandt
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Correspondence to Yves Van de Peer.

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Baele, G., Van de Peer, Y. & Vansteelandt, S. Using Non-Reversible Context-Dependent Evolutionary Models to Study Substitution Patterns in Primate Non-Coding Sequences. J Mol Evol 71, 34–50 (2010). https://doi.org/10.1007/s00239-010-9362-y

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  • DOI: https://doi.org/10.1007/s00239-010-9362-y

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