Protein Evolution

Catalog description

Consequences of evolution of protein-coding sequences: structures and functions. BMMB 533 Protein Evolution (2) Most biological functions are carried out by proteins, and evolutionary logic can be used to infer functions. This course will focus on evolution of protein-coding sequences, conformations and functions of proteins. Different species show varying characteristics of structure, metabolism, and regulatory control networks. Most of these differences are the product of the evolution of protein-coding sequences. DNA mutations can change amino acid sequences, protein structures and protein functions; and favorable mutations are selected, in ways that are integrated to form an organism adapted at both macroscopic and molecular levels. The availability of large databanks of protein amino acid sequences, and protein three-dimensional structures, and the annotation of protein function in the entries in these databanks, has allowed investigation of evolutionary changes that impact proteins. One of the goals of the course will be to describe these databanks and the computational tools available to apply them in research in molecular biology. Many students will find these tools useful in their own research projects. The evolutionary divergence of proteins has shown several types ofeffects. In some cases, related proteins in different species retain similar functions, but show differences in amino acid sequence and structure. The nature of observed changes in sequence and structure will be described and the relationship between sequence changes and structural changes examined in several well-documented examples, including globins, and serine proteases. In some cases, proteins diverge within a single species to form large families of related molecules with specialized functions. For example, the human genome encodes hundreds of odorant receptors. The comparison of related proteins that have adopted novel functions reveals how cells can expand their functional repertoire. In most cases it is easier to adapt an existing structure to a new function than to create a new protein "from scratch". For example, the proteolytic enzymes of the chymotrypsin family are related to haptoglobin, an iron scavenger that has lost its enzymatic activity. Beyond the description of individual proteins and individual protein families, there is the more general question of how changes in functions of individual proteins are integrated to create a smoothly-running cellular "operating system". The evolution of sequences encoding regulatory proteins to achieve this will be discussed. Methods of bioinformatics to address these questions will bepresented, with emphasis on study and comparison of structures with computer graphics.