ArticleMolecular biology and evolution2015
Toward more accurate ancestral protein genotype-phenotype reconstructions with the use of species tree-aware gene trees.
Article in Molecular biology and evolution, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed.
- Horizontal gene transfer and gene loss drove the divergent evolution of host dependency in Micrarchaeota.National science review · 2026Article
- Robustness of Ancestral Sequence Reconstruction to Among-site and Among-lineage Evolutionary Heterogeneity.Molecular biology and evolution · 2025Article
- Applications of ancestral sequence reconstruction for understanding the evolution of plant specialized metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Ancestral Reconstruction and the Evolution of Protein Energy Landscapes.Annual review of biophysics · 2024Review
- Parameter Estimation and Species Tree Rooting Using ALE and GeneRax.Genome biology and evolution · 2023Article
- ARPIP: Ancestral Sequence Reconstruction with Insertions and Deletions under the Poisson Indel Process.Systematic biology · 2023Article
- Evidence for existence of an apoptosis-inducing BH3-only protein, sayonara, in Drosophila.The EMBO journal · 2023Article
- Topiary: Pruning the manual labor from ancestral sequence reconstruction.Protein science : a publication of the Protein Society · 2023Article
- Ancestral reconstruction reveals catalytic inactivation of activation-induced cytidine deaminase concomitant with cold water adaption in the Gadiformes bony fish.BMC biology · 2022Article
- Probing the origin of prion protein misfolding via reconstruction of ancestral proteins.Protein science : a publication of the Protein Society · 2022Article
- Engineering functional thermostable proteins using ancestral sequence reconstruction.The Journal of biological chemistry · 2022Review
- Using the Evolutionary History of Proteins to Engineer Insertion-Deletion Mutants from Robust, Ancestral Templates Using Graphical Representation of Ancestral Sequence Predictions (GRASP).Methods in molecular biology (Clifton, N.J.) · 2022Article
- Ancestral sequence reconstruction - An underused approach to understand the evolution of gene function in plants?Computational and structural biotechnology journal · 2021Review
- Revenant: a database of resurrected proteins.Database : the journal of biological databases and curation · 2020Article
- Non-conservation of folding rates in the thioredoxin family reveals degradation of ancestral unassisted-folding.The Biochemical journal · 2019Article
- Genome size evolution in the Archaea.Emerging topics in life sciences · 2018Article
- Alignment Modulates Ancestral Sequence Reconstruction Accuracy.Molecular biology and evolution · 2018Article
- Crystal structure of an inferred ancestral bacterial pyruvate decarboxylase.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Conservation of Specificity in Two Low-Specificity Proteins.Biochemistry · 2018Article
- Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics.Systematic biology · 2017Article
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The resurrection of ancestral proteins provides direct insight into how natural selection has shaped proteins found in nature. By tracing substitutions along a gene phylogeny, ancestral proteins can be reconstructed in silico and subsequently synthesized in vitro. This elegant strategy reveals the complex mechanisms responsible for the evolution of protein functions and structures. However, to date, all protein resurrection studies have used simplistic approaches for ancestral sequence reconstruction (ASR), including the assumption that a single sequence alignment alone is sufficient to accurately reconstruct the history of the gene family. The impact of such shortcuts on conclusions about ancestral functions has not been investigated. Here, we show with simulations that utilizing information on species history using a model that accounts for the duplication, horizontal transfer, and loss (DTL) of genes statistically increases ASR accuracy. This underscores the importance of the tree topology in the inference of putative ancestors. We validate our in silico predictions using in vitro resurrection of the LeuB enzyme for the ancestor of the Firmicutes, a major and ancient bacterial phylum. With this particular protein, our experimental results demonstrate that information on the species phylogeny results in a biochemically more realistic and kinetically more stable ancestral protein. Additional resurrection experiments with different proteins are necessary to statistically quantify the impact of using species tree-aware gene trees on ancestral protein phenotypes. Nonetheless, our results suggest the need for incorporating both sequence and DTL information in future studies of protein resurrections to accurately define the genotype-phenotype space in which proteins diversify.
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