Networks of Protein Domain Architectures: Design Principles and Evolvability.

• Main Authors: Chia-Hsin Hus, 許嘉忻
• Other Authors: Ming-Jing Hwang
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/9h6wh9

博士 === 國立陽明大學 === 生物醫學資訊研究所 === 102 === Protein domain architectures (PDAs), which refer to the sequential linkage of protein domains that make up a protein chain, are a major molecular form used by evolution to diversify protein functions. However, the design principles of PDAs and how they have evolved remain poorly understood. These two aspects of PDAs are investigated in this dissertation by a network approach. In the first part of the dissertation, we constructed networks to connect PDAs that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. In the second part of the dissertation, we expanded the networks to include PDAs that do not share the same single domain but can be connected via a single evolutionary event. By analyzing PDA evolvability, defined as the number of network edges, and three other evolutionary properties in PDA networks constructed for three major life lineages (bacteria, fungi and metazoan), we found that proteins with PDAs of a higher level of evolvability, as indicated by having a greater number of connections in the PDA network, are present in a broader range of species. We also found that these proteins tend to be less essential to the organism, duplicate more often during evolution, have more isoforms, and, intriguingly, tend to be associated with functional categories important for organismal adaptation. These results reveal the presence of a core set of non-essential proteins commonly shared by many genomes that have a highly evolvable PDA and thus a greater potential for generating new functions through modifications in the protein domain architecture. Results from these two parts of works yield considerable insight into the design principles of protein structures and the factors that govern their evolution.