Dataset Information

The intrinsic dimension of protein sequence evolution.

ABSTRACT: It is well known that, in order to preserve its structure and function, a protein cannot change its sequence at random, but only by mutations occurring preferentially at specific locations. We here investigate quantitatively the amount of variability that is allowed in protein sequence evolution, by computing the intrinsic dimension (ID) of the sequences belonging to a selection of protein families. The ID is a measure of the number of independent directions that evolution can take starting from a given sequence. We find that the ID is practically constant for sequences belonging to the same family, and moreover it is very similar in different families, with values ranging between 6 and 12. These values are significantly smaller than the raw number of amino acids, confirming the importance of correlations between mutations in different sites. However, we demonstrate that correlations are not sufficient to explain the small value of the ID we observe in protein families. Indeed, we show that the ID of a set of protein sequences generated by maximum entropy models, an approach in which correlations are accounted for, is typically significantly larger than the value observed in natural protein families. We further prove that a critical factor to reproduce the natural ID is to take into consideration the phylogeny of sequences.

SUBMITTER: Facco E

PROVIDER: S-EPMC6472826 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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The intrinsic dimension of protein sequence evolution.

Facco Elena E Pagnani Andrea A Russo Elena Tea ET Laio Alessandro A

PLoS computational biology 20190408 4

It is well known that, in order to preserve its structure and function, a protein cannot change its sequence at random, but only by mutations occurring preferentially at specific locations. We here investigate quantitatively the amount of variability that is allowed in protein sequence evolution, by computing the intrinsic dimension (ID) of the sequences belonging to a selection of protein families. The ID is a measure of the number of independent directions that evolution can take starting from ...[more]

PMID: 30958823

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Project description:BackgroundWhile many authors have discussed models and tools for studying protein evolution at the sequence level, molecular function is usually mediated by complex, higher order features such as independently folding domains and linear motifs that are based on or embedded in a particular arrangment of features such as secondary structure elements, transmembrane domains and regions with intrinsic disorder. This 'protein architecture' can, in its most simplistic representation, be visualized as domain organization cartoons that can be used to compare proteins in terms of the order of their mostly globular domains.MethodologyHere, we describe a visual approach and a webserver for protein comparison that extend the domain organization cartoon concept. By developing an information-rich, compact visualization of different protein features above the sequence level, potentially related proteins can be compared at the level of propensities for secondary structure, transmembrane domains and intrinsic disorder, in addition to PFAM domains. A public Web server is available at www.proteinarchitect.net, while the code is provided at protarchitect.sourceforge.net.Conclusions/significanceDue to recent advances in sequencing technologies we are now flooded with millions of predicted proteins that await comparative analysis. In many cases, mature tools focused on revealing hits with considerable global or local similarity to well-characterized proteins will not be able to lead us to testable hypotheses about a protein's function, or the function of a particular region. The visual comparison of different types of protein features with ProteinArchitect will be useful when assessing the relevance of similarity search hits, to discover subgroups in protein families and superfamilies, and to understand protein regions with conserved features outside globular regions. Therefore, this approach is likely to help researchers to develop testable hypotheses about a protein's function even if is somewhat distant from the more characterized proteins, by facilitating the discovery of features that are conserved above the sequence level for comparison and further experimental investigation.

Dataset Information

The intrinsic dimension of protein sequence evolution.

Publications

The intrinsic dimension of protein sequence evolution.

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