uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Evolution and characteristics of the membrane proteome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Membrane proteins are found in all kingdoms of life and have a diverse set of functions and occupy key roles in many biological systems.  The majority of integral membrane proteins span the membrane with one or more transmembrane alpha helices, which both anchors the protein in the membrane and is crucial for their role in cell-cell interactions and signaling over the membrane. Herein, we have determined all alpha helical transmembrane proteins from 24 complete eukaryotic proteomes, which spans the four eukaryotic super groups chromalveolates, plants, excavates and unikonts. Hence, for the first time we are able to investigate the evolutionary history of the membrane proteome. In total we identify 100 955 membrane proteins among the more than 400 000 investigated proteins. We are able to place 91% of the membrane proteins into candidate families using Markov clustering based on sequence similarity and Pfam protein family affiliation. We provide evidence that most of the transporter and enzyme family repertoire of present eukaryotes was present already in the last common ancestor of all eukaryotes. Moreover, we discuss the functional nature of loss and gain of membrane protein families across eukaryotes and provide a comprehensive resource of the evolutionary history of the human membrane proteome.

Keyword [en]
Membrane proteins, membrane proteome, comparative genomics
National Category
Bioinformatics and Systems Biology Evolutionary Biology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-181981OAI: oai:DiVA.org:uu-181981DiVA: diva2:558203
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2013-01-23
In thesis
1. The Membrane Proteome: Evolution, Characteristics and Classification
Open this publication in new window or tab >>The Membrane Proteome: Evolution, Characteristics and Classification
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Membrane proteins are found in all kingdoms of life and are essential for cellular interactions with the environment. Although a large research effort have been put into this group many membrane proteins remains uncharacterized, both in terms of function and evolutionary history. We have estimated the component of α-helical membrane proteins within the human proteome; the membrane proteome. We found that the human membrane proteome make up 27% of all protein, which we could classify the majority of into 234 families and further into three major functional groups: receptors, transporters or enzymes. We extended this analysis by determining the membrane proteome of 24 organisms that covers all major groups of eukaryotes. This comprehensive membrane protein catalog of over 100,000 proteins was utilized to determine the evolutionary history of all membrane protein families throughout eukaryotes.  We also investigated the evolutionary history across eukaryotes of the antiviral Interferon induced transmembrane proteins (IFITM) and the G protein-coupled receptor (GPCR) superfamily in detail.  We identified ten novel human homologs to the IFITM proteins, which together with the known IFITMs forms a family that we call the Dispanins. Using phylogenetic analysis we show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and animals, and that the family later expanded in vertebrates into four subfamilies. The GPCR superfamily was mined across eukaryotic species and we present evidence for a common origin for four of the five main human GPCR families; Rhodopsin, Frizzled, Adhesion and Secretin in the cAMP receptor family that was found in non-metazoans and invertebrates, but has been lost in vertebrates. Here we present the first accurate estimation of the human proteome together with comprehensive functional and evolutionary classification and extend it to organisms that represents all major eukaryotic groups. Moreover, we identify a novel protein family, the Dispanins, which has an evolutionary history that has been formed by horizontal gene transfer from bacteria followed by expansions in the animal lineage. We also study the evolution of the GPCR superfamily throughout eukaryotic evolution and provide a comprehensive model of the evolution and relationship of these receptors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 35 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 818
Keyword
Membrane proteins, Membrane proteome, molecular evolution, GPCRs, Dispanins, IFITM
National Category
Evolutionary Biology Bioinformatics and Systems Biology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-181986 (URN)978-91-554-8484-2 (ISBN)
Public defence
2012-11-16, B22, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-10-26 Created: 2012-10-02 Last updated: 2013-01-23Bibliographically approved

Open Access in DiVA

No full text

By organisation
Functional Pharmacology
Bioinformatics and Systems BiologyEvolutionary BiologyBiochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 413 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf