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Title:Evolution of protein structure, function, and dynamics in biological systems
Author(s):Mughal, Fizza
Director of Research:Caetano-Anolles, Gustavo
Doctoral Committee Chair(s):Caetano-Anolles, Gustavo
Doctoral Committee Member(s):Hudson, Matthew E; Rodriguez-Zas, Sandra L; Zhao, Sihai Dave
Department / Program:Graduate College Programs
Discipline:Informatics
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Phylogenomics
Comparative genomics
Evolution
Protein Structure
Network Biology
Protein Flexibility
Abstract:Biological systems are complex entities comprising of parts that interact with each other within and across different levels of the hierarchy of biological organization to achieve common goals. We find that evolutionary constraints vary with different levels of granularity of the structure of biological systems. Different levels of organization and their parts often use similar strategies to achieve different goals. For example, at the organismal level cellular and viral proteomes leverage disorder to achieve advanced functionality and functional economy, respectively. Intrinsic disorder analysis at the protein domain level revealed that early protein domains were ordered and therefore, disorder is a benefit that was acquired later in evolution. In contrast, at the more granular level of protein secondary structure, we found that protein loops of ordered ancient fold families were highly disordered. Remarkably, the disorder analysis of protein loops uncovered the presence of ‘ordered’ loops, the existence of which could be explained by some molecular functions requiring a certain level of structural integrity, which is subsequently conserved to retain protein function. We surveyed pathways in biological systems to capture interactions of subnetworks and enzymes by analyzing evolving metabolic networks and find that hierarchical modularity is a key evolutionary principle of organization. Small world behavior increases at lower levels and decreases at higher levels of organization in evolving metabolic networks. Remarkably, we find similar small world tendencies in evolving dynamics networks of protein loops. Lastly, we present a structural morphospace to study these varying levels of organizations as well as the relationship between the order resulting from evolutionary constraints and intrinsic disorder that is also evolutionarily conserved. Structural morphospaces for dynamics networks, and evolving metabolic networks occupy regions that are reflective of the constraints acting on that specific level. We find that evolutionary constraints act on higher levels of organization following a biphasic pattern of diversification and growth, while optimizing for robustness. Moreover, evolution leverages disorder to maintain control, order and introduce innovation in the system.
Issue Date:2020-05-03
Type:Thesis
URI:http://hdl.handle.net/2142/108299
Rights Information:Copyright 2020 Fizza Mughal
Date Available in IDEALS:2020-08-27
Date Deposited:2020-05


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