--- _id: '1844' abstract: - lang: eng text: 'Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations.' author: - first_name: Valeria full_name: Risso, Valeria last_name: Risso - first_name: Fadia full_name: Manssour Triedo, Fadia last_name: Manssour Triedo - first_name: Asuncion full_name: Delgado Delgado, Asuncion last_name: Delgado Delgado - first_name: Rocio full_name: Arco, Rocio last_name: Arco - first_name: Alicia full_name: Barroso Deljesús, Alicia last_name: Barroso Deljesús - first_name: Álvaro full_name: Inglés Prieto, Álvaro id: 2A9DB292-F248-11E8-B48F-1D18A9856A87 last_name: Inglés Prieto orcid: 0000-0002-5409-8571 - first_name: Raquel full_name: Godoy Ruiz, Raquel last_name: Godoy Ruiz - first_name: Josè full_name: Gavira, Josè last_name: Gavira - first_name: Eric full_name: Gaucher, Eric last_name: Gaucher - first_name: Beatriz full_name: Ibarra Molero, Beatriz last_name: Ibarra Molero - first_name: Jose full_name: Sánchez Ruiz, Jose last_name: Sánchez Ruiz citation: ama: Risso V, Manssour Triedo F, Delgado Delgado A, et al. Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history. Molecular Biology and Evolution. 2014;32(2):440-455. doi:10.1093/molbev/msu312 apa: Risso, V., Manssour Triedo, F., Delgado Delgado, A., Arco, R., Barroso Deljesús, A., Inglés Prieto, Á., … Sánchez Ruiz, J. (2014). Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msu312 chicago: Risso, Valeria, Fadia Manssour Triedo, Asuncion Delgado Delgado, Rocio Arco, Alicia Barroso Deljesús, Álvaro Inglés Prieto, Raquel Godoy Ruiz, et al. “Mutational Studies on Resurrected Ancestral Proteins Reveal Conservation of Site-Specific Amino Acid Preferences throughout Evolutionary History.” Molecular Biology and Evolution. Oxford University Press, 2014. https://doi.org/10.1093/molbev/msu312. ieee: V. Risso et al., “Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history,” Molecular Biology and Evolution, vol. 32, no. 2. Oxford University Press, pp. 440–455, 2014. ista: Risso V, Manssour Triedo F, Delgado Delgado A, Arco R, Barroso Deljesús A, Inglés Prieto Á, Godoy Ruiz R, Gavira J, Gaucher E, Ibarra Molero B, Sánchez Ruiz J. 2014. Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history. Molecular Biology and Evolution. 32(2), 440–455. mla: Risso, Valeria, et al. “Mutational Studies on Resurrected Ancestral Proteins Reveal Conservation of Site-Specific Amino Acid Preferences throughout Evolutionary History.” Molecular Biology and Evolution, vol. 32, no. 2, Oxford University Press, 2014, pp. 440–55, doi:10.1093/molbev/msu312. short: V. Risso, F. Manssour Triedo, A. Delgado Delgado, R. Arco, A. Barroso Deljesús, Á. Inglés Prieto, R. Godoy Ruiz, J. Gavira, E. Gaucher, B. Ibarra Molero, J. Sánchez Ruiz, Molecular Biology and Evolution 32 (2014) 440–455. date_created: 2018-12-11T11:54:19Z date_published: 2014-11-12T00:00:00Z date_updated: 2021-01-12T06:53:34Z day: '12' ddc: - '571' department: - _id: HaJa doi: 10.1093/molbev/msu312 file: - access_level: open_access checksum: 06215318e66be8f3e0c33abb07e9d3da content_type: application/pdf creator: system date_created: 2018-12-12T10:16:56Z date_updated: 2020-07-14T12:45:19Z file_id: '5247' file_name: IST-2016-430-v1+1_Mol_Biol_Evol-2015-Risso-440-55.pdf file_size: 1545246 relation: main_file file_date_updated: 2020-07-14T12:45:19Z has_accepted_license: '1' intvolume: ' 32' issue: '2' language: - iso: eng license: https://creativecommons.org/licenses/by-nc/4.0/ month: '11' oa: 1 oa_version: Published Version page: 440 - 455 publication: Molecular Biology and Evolution publication_status: published publisher: Oxford University Press publist_id: '5257' pubrep_id: '430' quality_controlled: '1' scopus_import: 1 status: public title: Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 32 year: '2014' ...