dc.contributor.author |
Allison, Jane R |
|
dc.contributor.author |
Lechner, Marcus |
|
dc.contributor.author |
Hoeppner, Marc P |
|
dc.contributor.author |
Poole, Anthony M |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2022-05-11T04:32:59Z |
|
dc.date.available |
2022-05-11T04:32:59Z |
|
dc.date.issued |
2016-01 |
|
dc.identifier.citation |
(2016). PLoS One, 11(2), e0147619-. |
|
dc.identifier.issn |
1932-6203 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/59182 |
|
dc.description.abstract |
Evolutionary arms races between pathogens and their hosts may be manifested as selection for rapid evolutionary change of key genes, and are sometimes detectable through sequence-level analyses. In the case of protein-coding genes, such analyses frequently predict that specific codons are under positive selection. However, detecting positive selection can be non-trivial, and false positive predictions are a common concern in such analyses. It is therefore helpful to place such predictions within a structural and functional context. Here, we focus on the p19 protein from tombusviruses. P19 is a homodimer that sequesters siRNAs, thereby preventing the host RNAi machinery from shutting down viral infection. Sequence analysis of the p19 gene is complicated by the fact that it is constrained at the sequence level by overprinting of a viral movement protein gene. Using homology modeling, in silico mutation and molecular dynamics simulations, we assess how non-synonymous changes to two residues involved in forming the dimer interface-one invariant, and one predicted to be under positive selection-impact molecular function. Interestingly, we find that both observed variation and potential variation (where a non-synonymous change to p19 would be synonymous for the overprinted movement protein) does not significantly impact protein structure or RNA binding. Consequently, while several methods identify residues at the dimer interface as being under positive selection, MD results suggest they are functionally indistinguishable from a site that is free to vary. Our analyses serve as a caveat to using sequence-level analyses in isolation to detect and assess positive selection, and emphasize the importance of also accounting for how non-synonymous changes impact structure and function. |
|
dc.format.medium |
Electronic-eCollection |
|
dc.language |
eng |
|
dc.publisher |
Public Library of Science (PLoS) |
|
dc.relation.ispartofseries |
PloS one |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Tombusvirus |
|
dc.subject |
Lycopersicon esculentum |
|
dc.subject |
Viral Proteins |
|
dc.subject |
RNA |
|
dc.subject |
Crystallography, X-Ray |
|
dc.subject |
Sequence Alignment |
|
dc.subject |
Phylogeny |
|
dc.subject |
Plant Diseases |
|
dc.subject |
Gene Expression |
|
dc.subject |
Binding Sites |
|
dc.subject |
Amino Acid Sequence |
|
dc.subject |
Protein Structure, Secondary |
|
dc.subject |
Protein Binding |
|
dc.subject |
Sequence Homology, Amino Acid |
|
dc.subject |
Mutation |
|
dc.subject |
Molecular Sequence Data |
|
dc.subject |
Protein Interaction Domains and Motifs |
|
dc.subject |
Protein Multimerization |
|
dc.subject |
Selection, Genetic |
|
dc.subject |
Molecular Dynamics Simulation |
|
dc.subject |
Immune Evasion |
|
dc.subject |
Genetics |
|
dc.subject |
Prevention |
|
dc.subject |
1.1 Normal biological development and functioning |
|
dc.subject |
Generic health relevance |
|
dc.subject |
Infection |
|
dc.subject |
Science & Technology |
|
dc.subject |
Multidisciplinary Sciences |
|
dc.subject |
Science & Technology - Other Topics |
|
dc.subject |
RNA SILENCING SUPPRESSOR |
|
dc.subject |
MAXIMUM-LIKELIHOOD |
|
dc.subject |
BRANCH-SITE |
|
dc.subject |
VIRUS |
|
dc.subject |
EVOLUTION |
|
dc.subject |
GENES |
|
dc.subject |
DROSOPHILA |
|
dc.subject |
INTERFERENCE |
|
dc.subject |
SUBSTITUTION |
|
dc.subject |
RECOGNITION |
|
dc.subject |
0604 Genetics |
|
dc.title |
Positive Selection or Free to Vary? Assessing the Functional Significance of Sequence Change Using Molecular Dynamics. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1371/journal.pone.0147619 |
|
pubs.issue |
2 |
|
pubs.begin-page |
e0147619 |
|
pubs.volume |
11 |
|
dc.date.updated |
2022-04-28T03:02:21Z |
|
dc.rights.holder |
Copyright: The author |
en |
dc.identifier.pmid |
26871901 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/26871901 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
630167 |
|
pubs.org-id |
Science |
|
pubs.org-id |
Biological Sciences |
|
dc.identifier.eissn |
1932-6203 |
|
dc.identifier.pii |
PONE-D-15-31446 |
|
pubs.number |
ARTN e0147619 |
|
pubs.record-created-at-source-date |
2022-04-28 |
|
pubs.online-publication-date |
2016-02-12 |
|