Book of Abstracts: Albany 2003

category image Albany 2003
Conversation 13
Abstract Book
June 17-21 2003

Evolution of Intrinsically Unstructured Protein

Families of proteins having regions that form ensembles rather than single structures (i.e. intrinsically unstructured regions) have been subjected to two analyses: (i) estimation of the patterns of amino acid substitutions; and (ii) comparison of the evolutionary rates of ordered and disordered parts within the same protein. One of the most fundamental steps in bioinformatics is to align two or more sequences. Scoring matrices for amino acid sequence alignments are based primarily on fully folded, ordered proteins, but here we explore the development of a matrix adjusted to disordered regions. An iterative algorithm of realigning sequences and recalculating matrices will be presented. Results indicate an improved ability to detect and discriminate related disordered proteins. This improvement relates to an altered pattern of amino acid substitutions compared to ordered protein. To compare the evolutionary rates of ordered and disordered regions within the same proteins, pair-wise genetic distances were determined separately for each type of region for families having at least one member with a structurally-characterized region of disorder of 30 or more consecutive residues. For 5 families, there were no significant differences in pair-wise genetic distances between ordered and disordered sequences. The disordered region evolved significantly faster for 19 of 26 families, and the ordered region evolved faster in 2 families. No factor could be found to predict whether a disordered region would evolve faster or slower than the ordered regions of the same protein. Although disordered regions in general evolve faster than ordered regions perhaps because of reduced structural constraints, more work is needed to understand the underlying causes of the exceptions to this general trend.

Celeste J. Brown

University of Idaho
Moscow, ID 83844-3051
Phone: 208-885-9824
Fax: 208-885-7905