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Expansion of Protein Domain Repeats
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.ORCID iD: 0000-0002-7115-9751
2006 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 2, no 8, 959-970 p.Article in journal (Refereed) Published
Abstract [en]

Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e. g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

Place, publisher, year, edition, pages
2006. Vol. 2, no 8, 959-970 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:su:diva-25577DOI: 10.1371/journal.pcbi.0020114OAI: oai:DiVA.org:su-25577DiVA: diva2:200001
Note

Part of urn:nbn:se:su:diva-8295

Available from: 2008-11-06 Created: 2008-10-27 Last updated: 2014-11-10Bibliographically 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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Björklund, Åsa K.Elofsson, Arne
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