Molecular Evolution of Protein Domains Involved in Protein Turnover in Eukaryotes: A Comparative Genomics and ORFeomics Approach

Banerjee, Sumana (2013) Molecular Evolution of Protein Domains Involved in Protein Turnover in Eukaryotes: A Comparative Genomics and ORFeomics Approach. PhD thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Genome sequencing projects have produced vast quantities of data that are stored in different sequence repositories. Sequences in these databases are annotated taking input from different experimental methodologies and also computational techniques. Comparative genomics methods are usually based on the comparison of these sequences at the scale of whole genomes and generally rely on homology detection based on sequence similarity searches. This thesis presents an approach of comparative genomics wherein individual catalogues for protein domain families have been prepared and analyzed to derive additional insights into the functions of such proteins. Three key domains (FYVE, PX and UIM), which are involved in protein degradation pathways in eukaryotes were chosen for this study. This present approach has also facilitated the integration of functional information of these protein domain families with their taxonomic classification. So far experiments adopting biochemical and structural biology approaches have assisted in the identification and characterization of the aforesaid domain families. However, these studies have been conducted on proteins that were derived from a limited number of organisms. The inherent restrictions of genetic manoeuvrability, availability of tools such as expression vectors etc. have been the reasons for these constraints. However, since all the three domains included in this study are of fundamental importance to the functioning of the cell, they have been subjected to extensive studies; which have resulted in their detailed characterization. This pre-existing comprehensive knowledge has served as an excellent foundation for adopting bioinformatics approach to gain additional insights regarding the possible functions of these proteins, especially by encompassing data from organisms where biochemical studies are not possible. This study further strengthens the utility of whole genome comparison method in combining the wealth of information present in different sequence resources and assisting in the identification of new members of protein families that are encoded in less-studied organisms. As a whole, this thesis has uncovered various new aspects of the aforesaid three domain families.

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