Evolutionary innovations and the organization of protein functions in genotype space

The organization of protein structures in protein genotype space is well studied. The same does not hold for protein functions, whose organization is important to understand how novel protein functions can arise through blind evolutionary searches of sequence space. In systems other than proteins, t...

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Bibliographic Details
Published in:PloS one 2010-11, Vol.5 (11), p.e14172-e14172
Main Authors: Ferrada, Evandro, Wagner, Andreas
Format: Article
Language:English
Subjects:
Algorithms
Amino acid sequence
Amino acids
Binding Sites - genetics
Biocatalysis
Biochemistry
Biochemistry/Molecular Evolution
Bioinformatics
Computational Biology/Evolutionary Modeling
Databases, Protein
Deoxyribonucleic acid
Developmental biology
DNA
Ecosystem biology
Ecosystems
Enzymes
Enzymes - chemistry
Enzymes - metabolism
Evolution
Evolution, Molecular
Evolutionary biology
Evolutionary Biology/Bioinformatics
Genetic aspects
Genotype
Genotype & phenotype
Genotypes
Innovations
Mutation
Protein folding
Protein Structure, Tertiary
Proteins
Proteins - chemistry
Proteins - genetics
Proteins - metabolism
Structure-function relationships
Substrate Specificity
Trends
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Summary:The organization of protein structures in protein genotype space is well studied. The same does not hold for protein functions, whose organization is important to understand how novel protein functions can arise through blind evolutionary searches of sequence space. In systems other than proteins, two organizational features of genotype space facilitate phenotypic innovation. The first is that genotypes with the same phenotype form vast and connected genotype networks. The second is that different neighborhoods in this space contain different novel phenotypes. We here characterize the organization of enzymatic functions in protein genotype space, using a data set of more than 30,000 proteins with known structure and function. We show that different neighborhoods of genotype space contain proteins with very different functions. This property both facilitates evolutionary innovation through exploration of a genotype network, and it constrains the evolution of novel phenotypes. The phenotypic diversity of different neighborhoods is caused by the fact that some functions can be carried out by multiple structures. We show that the space of protein functions is not homogeneous, and different genotype neighborhoods tend to contain a different spectrum of functions, whose diversity increases with increasing distance of these neighborhoods in sequence space. Whether a protein with a given function can evolve specific new functions is thus determined by the protein's location in sequence space.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0014172