scholarly journals Accounting for ambiguity in ancestral sequence reconstruction

2018 ◽  
Author(s):  
A. Oliva ◽  
S. Pulicani ◽  
V. Lefort ◽  
L. Bréhélin ◽  
S. Guindon
Keyword(s):  
Molecular Evolution ◽  
The State ◽  
Ancestral Sequence ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction ◽  
Phylogenetic Framework ◽  
Genetic Sequences ◽  
Single State ◽  
New Criterion ◽  
Statistical Criteria

AbstractThe reconstruction of ancestral genetic sequences from the analysis of contemporaneous data is a powerful tool to improve our understanding of molecular evolution. Various statistical criteria defined in a phylogenetic framework can be used to infer nucleotide, aminoa-cid or codon states at internal nodes of the tree, for every position along the sequence. These criteria generally select the state that maximises (or minimises) a given criterion. Although it is perfectly sensible from a statistical perspective, that strategy fails to convey useful information about the level of uncertainty associated to the inference. The present study introduces a new criterion for ancestral nucleotide reconstruction that selects a single state whenever the signal conveyed by the data is strong, and a combination of multiple states otherwise. Simulations demonstrate the benefit of this approach with a substantial increase in the accuracy of ancestral sequence reconstruction without significantly compromising on the precision of the solutions returned.

scholarly journals Accounting for ambiguity in ancestral sequence reconstruction

2019 ◽  
Vol 35 (21) ◽  
pp. 4290-4297 ◽  
Author(s):  
A Oliva ◽  
S Pulicani ◽  
V Lefort ◽  
L Bréhélin ◽  
O Gascuel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Amino Acid Sequences ◽  
Ancestral Sequence ◽  
Tuning Parameters ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction ◽  
Phylogenetic Framework ◽  
Genetic Sequences ◽  
New Criterion

Abstract Motivation The reconstruction of ancestral genetic sequences from the analysis of contemporaneous data is a powerful tool to improve our understanding of molecular evolution. Various statistical criteria defined in a phylogenetic framework can be used to infer nucleotide, amino-acid or codon states at internal nodes of the tree, for every position along the sequence. These criteria generally select the state that maximizes (or minimizes) a given criterion. Although it is perfectly sensible from a statistical perspective, that strategy fails to convey useful information about the level of uncertainty associated to the inference. Results The present study introduces a new criterion for ancestral sequence reconstruction, the minimum posterior expected error (MPEE), that selects a single state whenever the signal conveyed by the data is strong, and a combination of multiple states otherwise. We also assess the performance of a criterion based on the Brier scoring scheme which, like MPEE, does not rely on any tuning parameters. The precision and accuracy of several other criteria that involve arbitrarily set tuning parameters are also evaluated. Large scale simulations demonstrate the benefits of using the MPEE and Brier-based criteria with a substantial increase in the accuracy of the inference of past sequences compared to the standard approach and realistic compromises on the precision of the solutions returned. Availability and implementation The software package PhyML (https://github.com/stephaneguindon/phyml) provides an implementation of the Maximum A Posteriori (MAP) and MPEE criteria for reconstructing ancestral nucleotide and amino-acid sequences.

scholarly journals Molecular coevolution of coagulation factor VIII and von Willebrand factor

2021 ◽  
Vol 5 (3) ◽  
pp. 812-822
Author(s):  
Philip M. Zakas ◽  
Christopher W. Coyle ◽  
Anja Brehm ◽  
Marion Bayer ◽  
Barbara Solecka-Witulska ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Coagulation Factor ◽  
Ancestral Sequence ◽  
Coagulation Factor Viii ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Ancestral sequence reconstruction provides a unique platform for investigating the molecular evolution of single gene products and recently has shown success in engineering advanced biological therapeutics. To date, the coevolution of proteins within complexes and protein–protein interactions is mostly investigated in silico via proteomics and/or within single-celled systems. Herein, ancestral sequence reconstruction is used to investigate the molecular evolution of 2 proteins linked not only by stabilizing association in circulation but also by their independent roles within the primary and secondary hemostatic systems of mammals. Using sequence analysis and biochemical characterization of recombinant ancestral von Willebrand factor (VWF) and coagulation factor VIII (FVIII), we investigated the evolution of the essential macromolecular FVIII/VWF complex. Our data support the hypothesis that these coagulation proteins coevolved throughout mammalian diversification, maintaining strong binding affinities while modulating independent and distinct hemostatic activities in diverse lineages.

Ancestral sequence reconstruction for protein engineers

2021 ◽  
Vol 69 ◽  
pp. 131-141
Author(s):  
Matthew A. Spence ◽  
Joe A. Kaczmarski ◽  
Jake W. Saunders ◽  
Colin J. Jackson
Keyword(s):  
Ancestral Sequence ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction

scholarly journals Ancestral sequence reconstruction produces thermally stable enzymes with mesophilic enzyme-like catalytic properties

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryutaro Furukawa ◽  
Wakako Toma ◽  
Koji Yamazaki ◽  
Satoshi Akanuma
Keyword(s):  
Low Temperature ◽  
Catalytic Properties ◽  
Amino Acid Sequences ◽  
Ancestral Sequence ◽  
Kinetic Properties ◽  
Reconstruction Technique ◽  
Thermally Stable ◽  
Ancestral Sequence Reconstruction ◽  
Ancestral Sequences ◽  
Sequence Reconstruction

Abstract Enzymes have high catalytic efficiency and low environmental impact, and are therefore potentially useful tools for various industrial processes. Crucially, however, natural enzymes do not always have the properties required for specific processes. It may be necessary, therefore, to design, engineer, and evolve enzymes with properties that are not found in natural enzymes. In particular, the creation of enzymes that are thermally stable and catalytically active at low temperature is desirable for processes involving both high and low temperatures. In the current study, we designed two ancestral sequences of 3-isopropylmalate dehydrogenase by an ancestral sequence reconstruction technique based on a phylogenetic analysis of extant homologous amino acid sequences. Genes encoding the designed sequences were artificially synthesized and expressed in Escherichia coli. The reconstructed enzymes were found to be slightly more thermally stable than the extant thermophilic homologue from Thermus thermophilus. Moreover, they had considerably higher low-temperature catalytic activity as compared with the T. thermophilus enzyme. Detailed analyses of their temperature-dependent specific activities and kinetic properties showed that the reconstructed enzymes have catalytic properties similar to those of mesophilic homologues. Collectively, our study demonstrates that ancestral sequence reconstruction can produce a thermally stable enzyme with catalytic properties adapted to low-temperature reactions.

scholarly journals Alignment Modulates Ancestral Sequence Reconstruction Accuracy

2018 ◽  
Vol 35 (7) ◽  
pp. 1783-1797 ◽  
Author(s):  
Ricardo Assunção Vialle ◽  
Asif U Tamuri ◽  
Nick Goldman
Keyword(s):  
Ancestral Sequence ◽  
Reconstruction Accuracy ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction

scholarly journals Sequence selection by FitSS4ASR alleviates ancestral sequence reconstruction as exemplified for geranylgeranylglyceryl phosphate synthase

2019 ◽  
Vol 400 (3) ◽  
pp. 367-381 ◽  
Author(s):  
Kristina Straub ◽  
Mona Linde ◽  
Cosimo Kropp ◽  
Samuel Blanquart ◽  
Patrick Babinger ◽  
...  
Keyword(s):  
Phylogenetic Signal ◽  
Phylogenetic Analyses ◽  
Specific Property ◽  
Ancestral Sequence ◽  
Rational Approach ◽  
Ancestral Sequence Reconstruction ◽  
Representative Sequence ◽  
Sequence Selection ◽  
Sequence Reconstruction ◽  
Phosphate Synthase

Abstract For evolutionary studies, but also for protein engineering, ancestral sequence reconstruction (ASR) has become an indispensable tool. The first step of every ASR protocol is the preparation of a representative sequence set containing at most a few hundred recent homologs whose composition determines decisively the outcome of a reconstruction. A common approach for sequence selection consists of several rounds of manual recompilation that is driven by embedded phylogenetic analyses of the varied sequence sets. For ASR of a geranylgeranylglyceryl phosphate synthase, we additionally utilized FitSS4ASR, which replaces this time-consuming protocol with an efficient and more rational approach. FitSS4ASR applies orthogonal filters to a set of homologs to eliminate outlier sequences and those bearing only a weak phylogenetic signal. To demonstrate the usefulness of FitSS4ASR, we determined experimentally the oligomerization state of eight predecessors, which is a delicate and taxon-specific property. Corresponding ancestors deduced in a manual approach and by means of FitSS4ASR had the same dimeric or hexameric conformation; this concordance testifies to the efficiency of FitSS4ASR for sequence selection. FitSS4ASR-based results of two other ASR experiments were added to the Supporting Information. Program and documentation are available at https://gitlab.bioinf.ur.de/hek61586/FitSS4ASR.

scholarly journals Ancestral Sequence Reconstruction in Primate Mitochondrial DNA: Compositional Bias and Effect on Functional Inference

2004 ◽  
Vol 21 (10) ◽  
pp. 1871-1883 ◽  
Author(s):  
Neeraja M. Krishnan ◽  
Hervé Seligmann ◽  
Caro-Beth Stewart ◽  
A. P. Jason de Koning ◽  
David D. Pollock
Keyword(s):  
Mitochondrial Dna ◽  
Ancestral Sequence ◽  
Compositional Bias ◽  
Ancestral Sequence Reconstruction ◽  
Sequence Reconstruction ◽  
Functional Inference
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