An experimental phylogeny to benchmark ancestral sequence reconstruction
Ryan N. Randall, Caelan E. Radford, Kelsey A. Roof, Divya K. Natarajan & Eric A. Gaucher
Nature Communications 7, Article number: 12847 (2016)
doi: 10.1038/ncomms12847
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Experimental evolution Phylogenetics
Received 01 April 2016 Accepted 05 August 2016 Published online 15 September 2016
Figure 1: Phylogram of the experimental phylogeny initiated from a single red FP gene.
Abstract
Ancestral sequence reconstruction (ASR) is a still-burgeoning method that has revealed many key mechanisms of molecular evolution. One criticism of the approach is an inability to validate its algorithms within a biological context as opposed to a computer simulation. Here we build an experimental phylogeny using the gene of a single red fluorescent protein to address this criticism. The evolved phylogeny consists of 19 operational taxonomic units (leaves) and 17 ancestral bifurcations (nodes) that display a wide variety of fluorescent phenotypes. The 19 leaves then serve as ‘modern’ sequences that we subject to ASR analyses using various algorithms and to benchmark against the known ancestral genotypes and ancestral phenotypes. We confirm computer simulations that show all algorithms infer ancient sequences with high accuracy, yet we also reveal wide variation in the phenotypes encoded by incorrectly inferred sequences. Specifically, Bayesian methods incorporating rate variation significantly outperform the maximum parsimony criterion in phenotypic accuracy. Subsampling of extant sequences had minor effect on the inference of ancestral sequences.
Acknowledgements
Funding was provided by the Georgia Institute of Technology, NASA (NNX12AI10G to E.A.G.), DuPont (Young Professor Award to E.A.G.) and NSF (grant 1145698 to E.A.G) We thank Andreas S. Bommarius for the mRFP1 gene, Barry G. Hall, Nathan Shaner, Joshua Weitz, and Zihang Yang for scientific discussions, and the following for assistance with building the experimental phylogeny: Kayla Arroyo, Krutika Gaonkar, Kristen Ingram, Penelope Kahn, Mark Leber, Byron Lee, Dione McKenzie, Angeline Pham, Lily Tran, Rebecca Wolf, and Zi-Ming Zhao.
Author information
Affiliations
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332, USA
Ryan N. Randall, Caelan E. Radford, Kelsey A. Roof, Divya K. Natarajan & Eric A. Gaucher
Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia 30332, USA
Eric A. Gaucher
Contributions
R.N.R. and E.A.G. conceived of the project and wrote the manuscript; R.N.R., C.E.R. and E.A.G. analysed results; R.N.R., C.E.R., K.A.R. and D.K.N performed the experiments.
Competing interests
The authors declare no competing financial interests.
Corresponding author
Correspondence to Eric A. Gaucher.
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