Early nitrogenase ancestors encompassed novel active site diversity
<jats:title>Abstract</jats:title> <jats:p>Ancestral sequence reconstruction (ASR) infers predicted ancestral states for sites within sequences and can constrain the functions and properties of ancestors of extant protein families. Here, we compare the likely sequenc...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press (OUP)
2023
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| Online Access: | https://hdl.handle.net/1721.1/148096 |
| _version_ | 1826189155092135936 |
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| author | Schwartz, Sarah L Garcia, Amanda K Kaçar, Betül Fournier, Gregory P |
| author2 | Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences Schwartz, Sarah L Garcia, Amanda K Kaçar, Betül Fournier, Gregory P |
| author_sort | Schwartz, Sarah L |
| collection | MIT |
| description | <jats:title>Abstract</jats:title>
<jats:p>Ancestral sequence reconstruction (ASR) infers predicted ancestral states for sites within sequences and can constrain the functions and properties of ancestors of extant protein families. Here, we compare the likely sequences of inferred nitrogenase ancestors to extant nitrogenase sequence diversity. We show that the most-likely combinations of ancestral states for key substrate channel residues are not represented in extant sequence space, and rarely found within a more broadly defined physiochemical space—supporting that the earliest ancestors of extant nitrogenases likely had alternative substrate channel composition. These differences may indicate differing environmental selection pressures acting on nitrogenase substrate specificity in ancient environments. These results highlight ASR's potential as an in silico tool for developing hypotheses about ancestral enzyme functions, as well as improving hypothesis testing through more targeted in vitro and in vivo experiments.</jats:p> |
| first_indexed | 2024-09-23T08:10:23Z |
| format | Article |
| id | mit-1721.1/148096 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:10:23Z |
| publishDate | 2023 |
| publisher | Oxford University Press (OUP) |
| record_format | dspace |
| spelling | mit-1721.1/1480962023-02-17T03:49:35Z Early nitrogenase ancestors encompassed novel active site diversity Schwartz, Sarah L Garcia, Amanda K Kaçar, Betül Fournier, Gregory P Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences <jats:title>Abstract</jats:title> <jats:p>Ancestral sequence reconstruction (ASR) infers predicted ancestral states for sites within sequences and can constrain the functions and properties of ancestors of extant protein families. Here, we compare the likely sequences of inferred nitrogenase ancestors to extant nitrogenase sequence diversity. We show that the most-likely combinations of ancestral states for key substrate channel residues are not represented in extant sequence space, and rarely found within a more broadly defined physiochemical space—supporting that the earliest ancestors of extant nitrogenases likely had alternative substrate channel composition. These differences may indicate differing environmental selection pressures acting on nitrogenase substrate specificity in ancient environments. These results highlight ASR's potential as an in silico tool for developing hypotheses about ancestral enzyme functions, as well as improving hypothesis testing through more targeted in vitro and in vivo experiments.</jats:p> 2023-02-16T17:37:02Z 2023-02-16T17:37:02Z 2022 2023-02-16T17:32:33Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/148096 Schwartz, Sarah L, Garcia, Amanda K, Kaçar, Betül and Fournier, Gregory P. 2022. "Early nitrogenase ancestors encompassed novel active site diversity." Molecular Biology and Evolution, 39 (11). en 10.1093/MOLBEV/MSAC226 Molecular Biology and Evolution Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Oxford University Press (OUP) Oxford University Press |
| spellingShingle | Schwartz, Sarah L Garcia, Amanda K Kaçar, Betül Fournier, Gregory P Early nitrogenase ancestors encompassed novel active site diversity |
| title | Early nitrogenase ancestors encompassed novel active site diversity |
| title_full | Early nitrogenase ancestors encompassed novel active site diversity |
| title_fullStr | Early nitrogenase ancestors encompassed novel active site diversity |
| title_full_unstemmed | Early nitrogenase ancestors encompassed novel active site diversity |
| title_short | Early nitrogenase ancestors encompassed novel active site diversity |
| title_sort | early nitrogenase ancestors encompassed novel active site diversity |
| url | https://hdl.handle.net/1721.1/148096 |
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