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The origin of conserved protein domains and amino acid repeats via adaptive competition for control over amino acid residues.

ABSTRACT: Some proteins, such as homeodomain transcription factors, contain highly conserved regions of sequence. It has recently been suggested that multiple functional domains overlap in the homeodomain, together explaining this high conservation. However, the question remains why so many functional domains cluster together in one relatively small and constrained region of the protein. Here we have modeled an evolutionary mechanism that can produce this kind of clustering: conserved functional domains are displaced from the parts of the molecule that are undergoing adaptive evolution because novel functions generally out-compete conserved functions for control over the identity of amino acid residues. We call this model COAA, for Competition Over Amino Acids. We also studied the evolution of amino acid repeats (a.k.a. homopeptides), which are especially prevalent in transcription factors. Repeats that are encoded by non-homogenous mixtures of synonymous codons cannot be explained by replication slippage alone. Our model provides two explanations for their origin, maintenance, and over-representation in highly conserved proteins. We demonstrate that either competition between multiple functional domains for space within a sequence, or reuse of a sequence for many functions over time, can cause the evolution of amino acid repeats. Both of these processes are characteristic of multifunctional proteins such as homeodomain transcription factors. We conclude that the COAA model can explain two widely recognized features of transcription factor proteins: conserved domains and a tendency to accumulate homopeptides.

SUBMITTER: Rorick MM

PROVIDER: S-EPMC3368225 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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The origin of conserved protein domains and amino acid repeats via adaptive competition for control over amino acid residues.

Rorick Mary M MM Wagner Günter P GP

Journal of molecular evolution 20091219 1

Some proteins, such as homeodomain transcription factors, contain highly conserved regions of sequence. It has recently been suggested that multiple functional domains overlap in the homeodomain, together explaining this high conservation. However, the question remains why so many functional domains cluster together in one relatively small and constrained region of the protein. Here we have modeled an evolutionary mechanism that can produce this kind of clustering: conserved functional domains a ...[more]

PMID: 20024539

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Project description:Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as "junk" sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in shaping the interaction networks of the human proteome, and define proteome-wide knowledge that may guide the informed biological exploration of the role of AARs in protein interactions.

Dataset Information

The origin of conserved protein domains and amino acid repeats via adaptive competition for control over amino acid residues.

Publications

The origin of conserved protein domains and amino acid repeats via adaptive competition for control over amino acid residues.

Similar Datasets

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