Phylointeractomics reconstructs functional evolution of protein binding.
Molecular phylogenomics investigates evolutionary relationships based on genomic data. However, despite genomic sequence conservation, changes in protein interactions can occur relatively rapidly and may cause strong functional diversification. To investigate such functional evolution, we here combine phylogenomics with interaction proteomics. We develop this concept by investigating the molecular evolution of the shelterin complex, which protects telomeres, across 16 vertebrate species from zebrafish to humans covering 450 million years of evolution. Our phylointeractomics screen discovers previously unknown telomere-associated proteins and reveals how homologous proteins undergo functional evolution. For instance, we show that TERF1 evolved as a telomere-binding protein in the common stem lineage of marsupial and placental mammals. Phylointeractomics is a versatile and scalable approach to investigate evolutionary changes in protein function and thus can provide experimental evidence for phylogenomic relationships.
Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore.|Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstraße 74, Dresden D-01307, Germany.
Dennis
0000-0002-3582-2253
D
Kappei
Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, Mainz D-55128, Germany.|Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany.
Marion
M
Scheibe
Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstraße 74, Dresden D-01307, Germany.
Maciej
M
Paszkowski-Rogacz
Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, Mainz D-55128, Germany.
Alina
A
Bluhm
Department of Animal &Plant Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Toni Ingolf
TI
Gossmann
Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, Mainz D-55128, Germany.
Sabrina
S
Dietz
Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, Mainz D-55128, Germany.
Mario
M
Dejung
Institute of Anthropology, University of Mainz, Anselm-Franz-von-Bentzel-Weg 7, Mainz D-55099, Germany.
Holger
H
Herlyn
Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstraße 74, Dresden D-01307, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden D-01307, Germany.|German Cancer Research Center (DKFZ), Neuenheimer Feld 280, 69120 Heidelberg, Germany.|German Cancer Consortium (DKTK) partner site, Fetscherstr. 74, 01307 Dresden Germany.|National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, TU Dresden, Dresden D-01307, Germany.
Frank
F
Buchholz
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany.
Matthias
M
Mann
Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, Mainz D-55128, Germany.
Falk
F
Butter
D000818:Animals; D002478:Cells, Cultured; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D016678:Genome; D023281:Genomics / Q000379:methods*; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics; D014714:Vertebrates / Q000235:genetics*
D034501:Telomere-Binding Proteins