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Domain Rearrangements in Protein Evolution
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2005 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 353, no 4, 911-923 p.Article in journal (Refereed) Published
Abstract [en]

Most eukaryotic proteins are multi-domain proteins that are created from fusions of genes, deletions and internal repetitions. An investigation of such evolutionary events requires a method to find the domain architecture from which each protein originates. Therefore, we defined a novel measure, domain distance, which is calculated as the number of domains that differ between two domain architectures. Using this measure the evolutionary events that distinguish a protein from its closest ancestor have been studied and it was found that indels are more common than internal repetition and that the exchange of a domain is rare. Indels and repetitions are common at both the N and C-terminals while they are rare between domains. The evolution of the majority of multi-domain proteins can be explained by the stepwise insertions of single domains, with the exception of repeats that sometimes are duplicated several domains in tandem. We show that domain distances agree with sequence similarity and semantic similarity based on gene ontology annotations. In addition, we demonstrate the use of the domain distance measure to build evolutionary trees. Finally, the evolution of multi-domain proteins is exemplified by a closer study of the evolution of two protein families, non-receptor tyrosine kinases and RhoGEFs.

Place, publisher, year, edition, pages
2005. Vol. 353, no 4, 911-923 p.
Keyword [en]
protein evolution; multi-domain proteins; proteome; GOGraph; Pfam
Identifiers
URN: urn:nbn:se:su:diva-25576DOI: 10.1016/j.jmb.2005.08.067OAI: oai:DiVA.org:su-25576DiVA: diva2:200000
Note
Part of urn:nbn:se:su:diva-8295Available from: 2008-11-06 Created: 2008-10-27 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Domain rearrangement and creation in protein evolution
Open this publication in new window or tab >>Domain rearrangement and creation in protein evolution
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Proteins are composed of domains, recurrent protein fragments with distinct structure, function and evolutionary history. Some domains exist only as single domain proteins, however, a majority of them are also combined with other domains. Domain rearrangements are important in the evolution of new proteins as new functionalities can arise in a single evolutionary event. In addition, the domain repertoire can be expanded through mutations of existing domains and de novo creation. The processes of domain rearrangement and creation have been the focus of this thesis.

According to our estimates about 65% of the eukaryotic and 40% of the prokaryotic proteins are of multidomain type. We found that insertion of a single domain at the N- or C-terminus was the most common event in the creation of novel multidomain architectures. However, domain repeats deviate from this pattern and are often expanded through duplications of several domains. Next, by mapping domain combinations onto an evolutionary tree we estimated that roughly one domain architecture has been created per million years, with the highest rates in metazoa. Much of this so called explosion of new architectures in metazoa seems to be explained by a set of domains amenable to exon shuffling. In contrast to domain architectures, most known domain families evolved early. However, many proteins have incomplete domain coverage, and could hence contain de novo created domains. In Saccharomyces cerevisiae, however, species specific sequences constitute only a minor fraction of the proteome, and are often short, disordered sequences located at the protein termini.

Place, publisher, year, edition, pages
Stockholm: Institutionen för biokemi och biofysik, 2008. 50 p.
National Category
Bioinformatics (Computational Biology)
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-8295 (URN)978-91-7155-767-4 (ISBN)
Public defence
2008-11-28, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
Opponent
Supervisors
Available from: 2008-11-06 Created: 2008-10-27Bibliographically approved
2. Creation of new proteins - domain rearrangements and tandem duplications
Open this publication in new window or tab >>Creation of new proteins - domain rearrangements and tandem duplications
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Proteins are modular entities with domains as their building blocks. The domains are recurrent protein fragments with a distinct structure, function and evolutionary history. During evolution, proteins with new functions have been invented through rearrangements as well as differentiation of domains. The focus of this thesis is to gain better understanding of the processes that govern domain rearrangements. In particular, the rearrangements that create long protein domain repeats have been investigated in detail.

We estimate that about 65% of the eukaryotic and 40% of the prokaryotic proteins are of the multidomain type. Further, we find that the eukaryotic multidomain proteins are mainly created through insertion of a single domain at the N- or C-terminus. However, domain repeats differ from other domain rearrangements in the aspect that they are created from internal tandem duplications. We show that such duplications often involve several domains simultaneously, and that different repeated domain families show distinct evolutionary patterns. Finally, we have investigated how large repeat regions are created using a specific example; the Actin binding nebulin domain. The analysis reveals several tandem duplications of both single nebulin domains and super repeats of seven nebulins in a number of vertebrates. We see that the duplication breakpoints vary between the species and that multiple duplications of the same region are common.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2010. 58 p.
National Category
Bioinformatics and Systems Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-37906 (URN)978-91-7447-032-1 (ISBN)
Public defence
2010-04-23, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 14:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2010-03-30 Created: 2010-03-23 Last updated: 2014-11-10Bibliographically approved

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