Linking fold, function and phylogeny: A comparative genomics view on protein (domain) evolution

Aartjan J.W. te Velthuis, Christoph P. Bagowski

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Domains are the building blocks of all globular proteins and present one of the most useful levels at which protein function can be understood. Through recombination and duplication of a limited set of domains, proteomes evolved and the collection of protein superfamilies in an organism formed. As such, the presence of a shared domain can be regarded as an indicator of similar function and evolutionary history, but it does not necessarily imply it since convergent evolution may give rise to similar gene functions as well as architectures. Through the wealth of sequences and annotation data brought about by genomics, evolutionary links can be sought for via homology relationships and comparative genomics, structural modeling and phylogenetics. The goal hereby is not only to predict the function of newly discovered proteins, but also to spell out their pathway of evolution and, possibly, identify their most likely origin. This can ultimately help to understand protein function and functional relationships of protein families. Additionally, through comparison with transcriptional data, evolutionary data can be linked to gene (and genome) activity and thus allow for the identification of common principles behind fast evolving proteins and relatively stable ones. In this review, we describe the basic principles of studying protein (domain) evolution and illustrate recent developments in molecular evolution and give valuable new insights in the field of comparative genomics. As an example, we include here molecular models of the multiple PDZ domain protein MUPP-1 and present a simple comparative genomic view on its structural course of evolution.

Original languageEnglish (US)
Pages (from-to)88-96
Number of pages9
JournalCurrent Genomics
Issue number2
StatePublished - Apr 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics


  • Alignment
  • Domain
  • MPDZ
  • MUPP
  • Molecular evolution
  • Molecular modeling
  • Multiple PDZ domain protein
  • PDZ
  • Phylogeny
  • Protein folding


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