ArticleGenome biology and evolution2020
Alignment-Integrated Reconstruction of Ancestral Sequences Improves Accuracy.
Article in Genome biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 21 citations in OpenAlex.
- Transaminases engineering and their cascade systems for natural product synthesis.Applied biochemistry and biotechnology · 2026Review
- Resurrecting Full-Length Ancestral Schizorhodopsins and Heliorhodopsins with Structure-Guided, Indel-Aware Sequence Reconstruction.ACS omega · 2026Article
- Advances and opportunities for computational interrogation of plant proteins.The Plant journal : for cell and molecular biology · 2026Review
- Ancestral Sequence Reconstruction for Designing Biocatalysts and Investigating their Functional Mechanisms.JACS Au · 2024Review
- 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
- Insertions and Deletions: Computational Methods, Evolutionary Dynamics, and Biological Applications.Molecular biology and evolution · 2024Review
- Designing cytochrome P450 enzymes for use in cancer gene therapy.Frontiers in bioengineering and biotechnology · 2024Review
- Experimental and computational analysis of the ancestry of an evolutionary young enzyme from histidine biosynthesis.Protein science : a publication of the Protein Society · 2023Article
- Engineering indel and substitution variants of diverse and ancient enzymes using Graphical Representation of Ancestral Sequence Predictions (GRASP).PLoS computational biology · 2022Article
- Engineering functional thermostable proteins using ancestral sequence reconstruction.The Journal of biological chemistry · 2022Review
- Ancestral sequence reconstruction as a tool to study the evolution of wood decaying fungi.Frontiers in fungal biology · 2022Review
- Ancestral Sequence Reconstruction for Exploring Alkaloid Evolution.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Resurrecting Enzymes by Ancestral Sequence Reconstruction.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Direct Molecular Evidence for an Ancient, Conserved Developmental Toolkit Controlling Posttranscriptional Gene Regulation in Land Plants.Molecular biology and evolution · 2021Article
- Setting the stage for evolution of a new enzyme.Current opinion in structural biology · 2021Review
- Ancestral Sequence Reconstruction: From Chemical Paleogenetics to Maximum Likelihood Algorithms and Beyond.Journal of molecular evolution · 2021Article
- Ancestral sequence reconstruction - An underused approach to understand the evolution of gene function in plants?Computational and structural biotechnology journal · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ancestral sequence reconstruction (ASR) uses an alignment of extant protein sequences, a phylogeny describing the history of the protein family and a model of the molecular-evolutionary process to infer the sequences of ancient proteins, allowing researchers to directly investigate the impact of sequence evolution on protein structure and function. Like all statistical inferences, ASR can be sensitive to violations of its underlying assumptions. Previous studies have shown that, whereas phylogenetic uncertainty has only a very weak impact on ASR accuracy, uncertainty in the protein sequence alignment can more strongly affect inferred ancestral sequences. Here, we show that errors in sequence alignment can produce errors in ASR across a range of realistic and simplified evolutionary scenarios. Importantly, sequence reconstruction errors can lead to errors in estimates of structural and functional properties of ancestral proteins, potentially undermining the reliability of analyses relying on ASR. We introduce an alignment-integrated ASR approach that combines information from many different sequence alignments. We show that integrating alignment uncertainty improves ASR accuracy and the accuracy of downstream structural and functional inferences, often performing as well as highly accurate structure-guided alignment. Given the growing evidence that sequence alignment errors can impact the reliability of ASR studies, we recommend that future studies incorporate approaches to mitigate the impact of alignment uncertainty. Probabilistic modeling of insertion and deletion events has the potential to radically improve ASR accuracy when the model reflects the true underlying evolutionary history, but further studies are required to thoroughly evaluate the reliability of these approaches under realistic conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.