Evolutionary Rate at the Protein Domain Level is Constrained by Importance to Network Dynamics

Persistent Link:
http://hdl.handle.net/10150/244452
Title:
Evolutionary Rate at the Protein Domain Level is Constrained by Importance to Network Dynamics
Author:
Mannakee, Brian Kendall
Issue Date:
May-2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
A fundamental question for evolutionary biology is why different proteins evolve at dramatically different rates. As the evolutionary time between two species and their common ancestor increases they accumulate a proportional number of amino acid changes between homologous proteins, but this proportional increase is not the same for all proteins. This difference in rate is attributed to the action of natural selection. While intuition suggests that natural selection acts most strongly to preserve and improve the function of proteins, little evidence supports this idea. Instead, the strongest predictor of protein evolutionary rate found to date is protein expression level, suggesting that selection acts primarily to prevent protein mis-folding. Here we suggest this apparent contradiction arises because the methods used to measure protein functional importance are ill-suited to capture the subtle interplay between protein structure and function. We introduce a measure of functional importance called Dynamical Influence, leveraging computational models of cellular systems for a much finer view of the functional importance of a protein in its network context. Comparing this measure with protein evolutionary rates across the vertebrate evolutionary tree we find strong evidence that selection operates to preserve and refine protein function to a much greater extent than previously observed.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Biochemistry and Molecular Biophysics
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleEvolutionary Rate at the Protein Domain Level is Constrained by Importance to Network Dynamicsen_US
dc.creatorMannakee, Brian Kendallen_US
dc.contributor.authorMannakee, Brian Kendallen_US
dc.date.issued2012-05-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractA fundamental question for evolutionary biology is why different proteins evolve at dramatically different rates. As the evolutionary time between two species and their common ancestor increases they accumulate a proportional number of amino acid changes between homologous proteins, but this proportional increase is not the same for all proteins. This difference in rate is attributed to the action of natural selection. While intuition suggests that natural selection acts most strongly to preserve and improve the function of proteins, little evidence supports this idea. Instead, the strongest predictor of protein evolutionary rate found to date is protein expression level, suggesting that selection acts primarily to prevent protein mis-folding. Here we suggest this apparent contradiction arises because the methods used to measure protein functional importance are ill-suited to capture the subtle interplay between protein structure and function. We introduce a measure of functional importance called Dynamical Influence, leveraging computational models of cellular systems for a much finer view of the functional importance of a protein in its network context. Comparing this measure with protein evolutionary rates across the vertebrate evolutionary tree we find strong evidence that selection operates to preserve and refine protein function to a much greater extent than previously observed.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplineBiochemistry and Molecular Biophysicsen_US
thesis.degree.grantorUniversity of Arizonaen_US
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