Evolution of Multidomain Proteins CS374 Fall 2006 Lecture 10, 10/24/06 Lecturer: Wissam Kazan Scribe: Mayukh Bhaowal Evolution of Multidomain Proteins Relevant Literature • C. Chothia, J. Gough, C. Vogel, S. A. Teichmann, “Evolution of the Protein Repertoire”, www.sciencemag.com, Science VOL 300, 13 June 2003 • T. Przytycka, G. Davis, N. Song, D. Durand, “Graph Theoretical Insights into Evolution of Multidomain Proteins”, RECOMB 2005, LNBI 3500, pp. 311-325, 2005 Table of Contents 1. Proteins and their functions …………………………………………………………1 1.1 Protein Domains ………………………………………………………………... 2 1.2 Domain Family …………………………………………………………………..2 2. Increase in the protein repertoire ……………………………………………………3 3. Analysis of Evolution ……………………………………………………………….4 3.1. Protein Repertoire ………………………………………………………………4 3.2. Domain Combinations ………………………………………………………….5 3.3. Supra Domains ………………………………………………………………….6 4. Metabolic Pathway Formation ……………………………………………………..7 5. Multidomain Protein Mystery ……………………………………………………...7 6. Protein Family Analysis ……………………………………………………………8 7. Parsimony Model …………………………………………………………………...8 7.1. Dollo Parsimony ……………………………………………………………….9 7.2. Digression: maximum parsimony example ……………………………………9 8. Evolution of Multidomain Proteins ………………………………………………..11 8.1. Protein Overlap Graph ………………………………………………………...12 8.2. Domain Overlap Graph ………………………………………………………..12 8.3. Static Dollo Parsimony ………………………………………………………...12 8.4. Conservative Dollo Parsimony ………………………………………………...13 8.5. Motivation of Using Parsimony ……………………………………………….13 9. Analyzing the Graph ………………………………………………………………13 10. Experimental Results ……………………………………………………………...15 1. Proteins and their functions These are large Organic Compounds made of amino acids which fold into specific Structures, unique to each protein. These proteins are functionally extremely important. Proteins are chief actors in the cell. They bind to other molecules specifically and tightlyEvolution of Multidomain Proteins CS374 Fall 2006 Lecture 10, 10/24/06 Lecturer: Wissam Kazan Scribe: Mayukh Bhaowal at the binding site. Besides, they act as enzymes to catalyze chemical reactions. Antibodies are proteins that bind to antigen and target them for destruction 1.1 Protein Domains They are primary constituent of proteins. It is a conserved evolutionary structural unit: 1. Assumed to fold independently 2. Observed in different proteins in the context of different neighboring domains 3. Whose coding sequence can be duplicated and/or undergo recombination Small proteins contain just one domain while larger proteins are formed by combination of domains. These domains are generally endowed with a specific functionality. Hence they play a very important role functionally. Example of such a domain can be the binding domain. The length of the domains can range arbitrarily but in general fall between 100 to 250 nucleotides long. a. protein Zif268 (blue) containing three zinc fingers domains in complex with DNA (orange). The coordinating amino acid residues of the middle zinc ion (green) are highlighted. b. Binding Domain 1.2 Domain Family A domain family is a collection of small proteins and/or parts of larger ones that descend from a common ancestor. The following diagram depicts the PR domain family members:Evolution of Multidomain Proteins CS374 Fall 2006 Lecture 10, 10/24/06 Lecturer: Wissam Kazan Scribe: Mayukh Bhaowal It is very important for us to know the domain family relationships. However there are several hindrances towards this end. Namely, it is kind of difficult to discover distant relationships between protein families. A prior knowledge of the protein 3-D structure does help. We only know family relationships and domain structures of proteins of known structures or proteins homologous to proteins of known structures. This leads to the important fact that the numbers of members in a protein family follow a Pareto distribution. This idea is sometimes expressed more simply as the Pareto principle or the "80-20 rule" which says that 20% of the population owns 80% of the wealth. Thus in this case it simply states that few families have many members whereas many families have few members. The basic intuition being the functional aspects of few families. Since their properties molecular functions, they tend to have more members. 2. Increase in the protein repertoire There are several actions going on which results in the increase in the protein repertoire. This includes the duplication of coding sequences for one or more domain, divergence ofEvolution of Multidomain Proteins CS374 Fall 2006 Lecture 10, 10/24/06 Lecturer: Wissam Kazan Scribe: Mayukh Bhaowal duplicated sequences by mutations, deletions and insertions producing modified structures that may have useful new properties and recombination of genes that results in new arrangements of domains. These mechanisms have long been believed to be the source of new proteins, and rates at which they occur have been calculated recently. The new findings discussed here come from the use of structural information to analyze genome sequences. This provides for the first time a quantitative view of the nature and extent of these processes. The authors
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