Dataset Information

Inferring functional constraints and divergence in protein families using 3D mapping of phylogenetic information.

ABSTRACT: Comparative sequence analysis has been used to study specific questions about the structure and function of proteins for many years. Here we propose a knowledge-based framework in which the maximum likelihood rate of evolution is used to quantify the level of constraint on the identity of a site. We demonstrate that site-rate mapping on 3D structures using datasets of rhodopsin-like G-protein receptors and alpha- and beta-tubulins provides an excellent tool for pinpointing the functional features shared between orthologous and paralogous proteins. In addition, functional divergence within protein families can be inferred by examining the differences in the site rates, the differences in the chemical properties of the side chains or amino acid usage between aligned sites. Two novel analytical methods are introduced to characterize rate- independent functional divergence. These are tested using a dataset of two classes of HMG-CoA reductases for which only one class can perform both the forward and reverse reaction. We show that functionally divergent sites occur in a cluster of sites interacting with the catalytic residues and that this information should facilitate the design of experimental strategies to directly test functional properties of residues.

SUBMITTER: Blouin C

PROVIDER: S-EPMC140515 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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Inferring functional constraints and divergence in protein families using 3D mapping of phylogenetic information.

Blouin Christian C Boucher Yan Y Roger Andrew J AJ

Nucleic acids research 20030101 2

Comparative sequence analysis has been used to study specific questions about the structure and function of proteins for many years. Here we propose a knowledge-based framework in which the maximum likelihood rate of evolution is used to quantify the level of constraint on the identity of a site. We demonstrate that site-rate mapping on 3D structures using datasets of rhodopsin-like G-protein receptors and alpha- and beta-tubulins provides an excellent tool for pinpointing the functional feature ...[more]

PMID: 12527789

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Project description:Understanding the influences of dispersal limitation and environmental filtering on the structure of ecological communities is a major challenge in ecology. Insight may be gained by combining phylogenetic, functional and taxonomic data to characterize spatial turnover in community structure (?-diversity). We develop a framework that allows rigorous inference of the strengths of dispersal limitation and environmental filtering by combining these three types of ?-diversity. Our framework provides model-generated expectations for patterns of taxonomic, phylogenetic and functional ?-diversity across biologically relevant combinations of dispersal limitation and environmental filtering. After developing the framework we compared the model-generated expectations to the commonly used "intuitive" expectation that the variance explained by the environment or by space will, respectively, increase monotonically with the strength of environmental filtering or dispersal limitation. The model-generated expectations strongly departed from these intuitive expectations: the variance explained by the environment or by space was often a unimodal function of the strength of environmental filtering or dispersal limitation, respectively. Therefore, although it is commonly done in the literature, one cannot assume that the strength of an underlying process is a monotonic function of explained variance. To infer the strength of underlying processes, one must instead compare explained variances to model-generated expectations. Our framework provides these expectations. We show that by combining the three types of ?-diversity with model-generated expectations our framework is able to provide rigorous inferences of the relative and absolute strengths of dispersal limitation and environmental filtering. Phylogenetic, functional and taxonomic ?-diversity can therefore be used simultaneously to infer processes by comparing their empirical patterns to the expectations generated by frameworks similar to the one developed here.

Dataset Information

Inferring functional constraints and divergence in protein families using 3D mapping of phylogenetic information.

Publications

Inferring functional constraints and divergence in protein families using 3D mapping of phylogenetic information.

Similar Datasets

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