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Nebulin: A Study of Protein Repeat 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.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0002-7115-9751
2010 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 402, no 1, 38-51 p.Article in journal (Refereed) Published
Abstract [en]

Protein domain repeats are common in proteins that are central to the organization of a cell, in particular in eukaryotes. They are known to evolve through internal tandem duplications. However, the understanding of the underlying mechanisms is incomplete. To shed light on repeat expansion mechanisms, we have studied the evolution of the muscle protein Nebulin, a protein that contains a large number of actin-binding nebulin domains. Nebulin proteins have evolved from an invertebrate precursor containing two nebulin domains. Repeat regions have expanded through duplications of single domains, as well as duplications of a super repeat (SR) consisting of seven nebulins. We show that the SR has evolved independently into large regions in at least three instances: twice in the invertebrate Branchiostoma floridae and once in vertebrates. In-depth analysis reveals several recent tandem duplications in the Nebulin gene. The events involve both single-domain and multidomain SR units or several SR units. There are single events, but frequently the same unit is duplicated multiple times. For instance, an ancestor of human and chimpanzee underwent two tandem duplications. The duplication junction coincides with an Alu transposon, thus suggesting duplication through Alu-mediated homologous recombination. Duplications in the SR region consistently involve multiples of seven domains. However, the exact unit that is duplicated varies both between species and within species. Thus, multiple tandem duplications of the same motif did not create the large Nebulin protein. Finally, analysis of segmental duplications in the human genome reveals that duplications are more common in genes containing domain repeats than in those coding for nonrepeated proteins. In fact, segmental duplications are found three to six times more often in long repeated genes than expected by chance. 

Place, publisher, year, edition, pages
2010. Vol. 402, no 1, 38-51 p.
Keyword [en]
protein domain repeat, evolution, repeat duplication, segmental duplication, Nebulin
National Category
Bioinformatics and Systems Biology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:su:diva-50177DOI: 10.1016/j.jmb.2010.07.011ISI: 000282074500005PubMedID: 20643138OAI: oai:DiVA.org:su-50177DiVA: diva2:381919
Note

authorCount :4

Available from: 2010-12-29 Created: 2010-12-21 Last updated: 2017-12-11Bibliographically approved
In thesis
1. 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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