Cargando…
Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability
Since divergence ∼50 Ma ago from their terrestrial ancestors, cetaceans underwent a series of adaptations such as a ∼10–20 fold increase in myoglobin (Mb) concentration in skeletal muscle, critical for increasing oxygen storage capacity and prolonging dive time. Whereas the O(2)-binding affinity of...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591298/ https://www.ncbi.nlm.nih.gov/pubmed/23505347 http://dx.doi.org/10.1371/journal.pcbi.1002929 |
_version_ | 1782262024970960896 |
---|---|
author | Dasmeh, Pouria Serohijos, Adrian W. R. Kepp, Kasper P. Shakhnovich, Eugene I. |
author_facet | Dasmeh, Pouria Serohijos, Adrian W. R. Kepp, Kasper P. Shakhnovich, Eugene I. |
author_sort | Dasmeh, Pouria |
collection | PubMed |
description | Since divergence ∼50 Ma ago from their terrestrial ancestors, cetaceans underwent a series of adaptations such as a ∼10–20 fold increase in myoglobin (Mb) concentration in skeletal muscle, critical for increasing oxygen storage capacity and prolonging dive time. Whereas the O(2)-binding affinity of Mbs is not significantly different among mammals (with typical oxygenation constants of ∼0.8–1.2 µM(−1)), folding stabilities of cetacean Mbs are ∼2–4 kcal/mol higher than for terrestrial Mbs. Using ancestral sequence reconstruction, maximum likelihood and Bayesian tests to describe the evolution of cetacean Mbs, and experimentally calibrated computation of stability effects of mutations, we observe accelerated evolution in cetaceans and identify seven positively selected sites in Mb. Overall, these sites contribute to Mb stabilization with a conditional probability of 0.8. We observe a correlation between Mb folding stability and protein abundance, suggesting that a selection pressure for stability acts proportionally to higher expression. We also identify a major divergence event leading to the common ancestor of whales, during which major stabilization occurred. Most of the positively selected sites that occur later act against other destabilizing mutations to maintain stability across the clade, except for the shallow divers, where late stability relaxation occurs, probably due to the shorter aerobic dive limits of these species. The three main positively selected sites 66, 5, and 35 undergo changes that favor hydrophobic folding, structural integrity, and intra-helical hydrogen bonds. |
format | Online Article Text |
id | pubmed-3591298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35912982013-03-15 Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability Dasmeh, Pouria Serohijos, Adrian W. R. Kepp, Kasper P. Shakhnovich, Eugene I. PLoS Comput Biol Research Article Since divergence ∼50 Ma ago from their terrestrial ancestors, cetaceans underwent a series of adaptations such as a ∼10–20 fold increase in myoglobin (Mb) concentration in skeletal muscle, critical for increasing oxygen storage capacity and prolonging dive time. Whereas the O(2)-binding affinity of Mbs is not significantly different among mammals (with typical oxygenation constants of ∼0.8–1.2 µM(−1)), folding stabilities of cetacean Mbs are ∼2–4 kcal/mol higher than for terrestrial Mbs. Using ancestral sequence reconstruction, maximum likelihood and Bayesian tests to describe the evolution of cetacean Mbs, and experimentally calibrated computation of stability effects of mutations, we observe accelerated evolution in cetaceans and identify seven positively selected sites in Mb. Overall, these sites contribute to Mb stabilization with a conditional probability of 0.8. We observe a correlation between Mb folding stability and protein abundance, suggesting that a selection pressure for stability acts proportionally to higher expression. We also identify a major divergence event leading to the common ancestor of whales, during which major stabilization occurred. Most of the positively selected sites that occur later act against other destabilizing mutations to maintain stability across the clade, except for the shallow divers, where late stability relaxation occurs, probably due to the shorter aerobic dive limits of these species. The three main positively selected sites 66, 5, and 35 undergo changes that favor hydrophobic folding, structural integrity, and intra-helical hydrogen bonds. Public Library of Science 2013-03-07 /pmc/articles/PMC3591298/ /pubmed/23505347 http://dx.doi.org/10.1371/journal.pcbi.1002929 Text en © 2013 Dasmeh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dasmeh, Pouria Serohijos, Adrian W. R. Kepp, Kasper P. Shakhnovich, Eugene I. Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability |
title | Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability |
title_full | Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability |
title_fullStr | Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability |
title_full_unstemmed | Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability |
title_short | Positively Selected Sites in Cetacean Myoglobins Contribute to Protein Stability |
title_sort | positively selected sites in cetacean myoglobins contribute to protein stability |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591298/ https://www.ncbi.nlm.nih.gov/pubmed/23505347 http://dx.doi.org/10.1371/journal.pcbi.1002929 |
work_keys_str_mv | AT dasmehpouria positivelyselectedsitesincetaceanmyoglobinscontributetoproteinstability AT serohijosadrianwr positivelyselectedsitesincetaceanmyoglobinscontributetoproteinstability AT keppkasperp positivelyselectedsitesincetaceanmyoglobinscontributetoproteinstability AT shakhnovicheugenei positivelyselectedsitesincetaceanmyoglobinscontributetoproteinstability |