Exploring the evolution of novel enzyme functions within structurally defined protein superfamilies

In order to understand the evolution of enzyme reactions and to gain an overview of biological catalysis we have combined sequence and structural data to generate phylogenetic trees in an analysis of 276 structurally defined enzyme superfamilies, and used these to study how enzyme functions have evo...

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Bibliographic Details
Published in:PLoS computational biology 2012-03, Vol.8 (3), p.e1002403-e1002403
Main Authors: Furnham, Nicholas, Sillitoe, Ian, Holliday, Gemma L, Cuff, Alison L, Laskowski, Roman A, Orengo, Christine A, Thornton, Janet M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biology
Chemistry
Classification
Computational biology
Enzymes
Enzymes - chemistry
Enzymes - physiology
Evolution
Evolution, Molecular
Experiments
Molecular evolution
Molecular Sequence Data
Phylogenetics
Physiological aspects
Proteins
Sequence Analysis, Protein - methods
Structure-Activity Relationship
Trees
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Summary:In order to understand the evolution of enzyme reactions and to gain an overview of biological catalysis we have combined sequence and structural data to generate phylogenetic trees in an analysis of 276 structurally defined enzyme superfamilies, and used these to study how enzyme functions have evolved. We describe in detail the analysis of two superfamilies to illustrate different paradigms of enzyme evolution. Gathering together data from all the superfamilies supports and develops the observation that they have all evolved to act on a diverse set of substrates, whilst the evolution of new chemistry is much less common. Despite that, by bringing together so much data, we can provide a comprehensive overview of the most common and rare types of changes in function. Our analysis demonstrates on a larger scale than previously studied, that modifications in overall chemistry still occur, with all possible changes at the primary level of the Enzyme Commission (E.C.) classification observed to a greater or lesser extent. The phylogenetic trees map out the evolutionary route taken within a superfamily, as well as all the possible changes within a superfamily. This has been used to generate a matrix of observed exchanges from one enzyme function to another, revealing the scale and nature of enzyme evolution and that some types of exchanges between and within E.C. classes are more prevalent than others. Surprisingly a large proportion (71%) of all known enzyme functions are performed by this relatively small set of 276 superfamilies. This reinforces the hypothesis that relatively few ancient enzymatic domain superfamilies were progenitors for most of the chemistry required for life.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1002403