---
_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.'
article_processing_charge: No
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. <i>Molecular Biology and Evolution</i>.
    2014;32(2):440-455. doi:<a href="https://doi.org/10.1093/molbev/msu312">10.1093/molbev/msu312</a>
  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. <i>Molecular Biology and Evolution</i>. Oxford
    University Press. <a href="https://doi.org/10.1093/molbev/msu312">https://doi.org/10.1093/molbev/msu312</a>
  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.” <i>Molecular Biology
    and Evolution</i>. Oxford University Press, 2014. <a href="https://doi.org/10.1093/molbev/msu312">https://doi.org/10.1093/molbev/msu312</a>.
  ieee: V. Risso <i>et al.</i>, “Mutational studies on resurrected ancestral proteins
    reveal conservation of site-specific amino acid preferences throughout evolutionary
    history,” <i>Molecular Biology and Evolution</i>, 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.” <i>Molecular Biology and Evolution</i>, vol. 32, no. 2, Oxford University
    Press, 2014, pp. 440–55, doi:<a href="https://doi.org/10.1093/molbev/msu312">10.1093/molbev/msu312</a>.
  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: 2025-09-29T13:11:19Z
day: '12'
ddc:
- '571'
department:
- _id: HaJa
doi: 10.1093/molbev/msu312
external_id:
  isi:
  - '000350050700012'
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'
isi: 1
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 32
year: '2014'
...