Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees
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 c...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Oxford University Press
2015
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| Online Access: | http://hdl.handle.net/1721.1/96705 https://orcid.org/0000-0002-0942-7217 |
| _version_ | 1826203851642896384 |
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| author | Groussin, Mathieu Hobbs, Joanne K. Szöllősi, Gergely J. Gribaldo, Simonetta Arcus, Vickery L. Gouy, Manolo |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Groussin, Mathieu Hobbs, Joanne K. Szöllősi, Gergely J. Gribaldo, Simonetta Arcus, Vickery L. Gouy, Manolo |
| author_sort | Groussin, Mathieu |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:44:18Z |
| format | Article |
| id | mit-1721.1/96705 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:44:18Z |
| publishDate | 2015 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/967052022-10-01T10:48:17Z Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees Groussin, Mathieu Hobbs, Joanne K. Szöllősi, Gergely J. Gribaldo, Simonetta Arcus, Vickery L. Gouy, Manolo Massachusetts Institute of Technology. Department of Biological Engineering Groussin, Mathieu 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. European Social Fund (framework of TAMOP 4.2.4. A/1-11-1-2012-0001 “National Excellence Program”) European Union (Albert Szent-Gyorgyi Call-Home Researcher Scholarship A1-SZGYA-FOK-13-0005) European Union (Marie Curie CIG 618438 “Genestory”) France. Agence nationale de la recherche (Ancestrome project (ANR-10-BINF-01-01)) 2015-04-22T18:05:28Z 2015-04-22T18:05:28Z 2014-11 Article http://purl.org/eprint/type/JournalArticle 0737-4038 1537-1719 http://hdl.handle.net/1721.1/96705 Groussin, M., J. K. Hobbs, G. J. Szoll si, S. Gribaldo, V. L. Arcus, and M. Gouy. “Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees.” Molecular Biology and Evolution 32, no. 1 (November 4, 2014): 13–22. https://orcid.org/0000-0002-0942-7217 en_US http://dx.doi.org/10.1093/molbev/msu305 Molecular Biology and Evolution Creative Commons Attribution http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Oxford University Press Oxford University Press |
| spellingShingle | Groussin, Mathieu Hobbs, Joanne K. Szöllősi, Gergely J. Gribaldo, Simonetta Arcus, Vickery L. Gouy, Manolo Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees |
| title | Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees |
| title_full | Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees |
| title_fullStr | Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees |
| title_full_unstemmed | Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees |
| title_short | Toward More Accurate Ancestral Protein Genotype-Phenotype Reconstructions with the Use of Species Tree-Aware Gene Trees |
| title_sort | toward more accurate ancestral protein genotype phenotype reconstructions with the use of species tree aware gene trees |
| url | http://hdl.handle.net/1721.1/96705 https://orcid.org/0000-0002-0942-7217 |
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