Abstract
AbstractTogether with the platelet-derived growth factors (PDGFs), the vascular endothelial growth factors (VEGFs) form the PDGF/VEGF subgroup among cystine knot growth factors. The evolutionary relationships within this subgroup have not been examined thoroughly to date. Here, we comprehensively analyze the PDGF/VEGF growth factors throughout all animal phyla and propose a phylogenetic tree. Vertebrate whole-genome duplications play a role in expanding PDGF/VEGF diversity, but several limited duplications are necessary to account for the temporal pattern of emergence. The phylogenetically oldest PDGF/VEGF-like growth factor likely featured a C-terminus with a BR3P signature, a hallmark of the modern-day lymphangiogenic growth factors VEGF-C and VEGF-D. Some younger VEGF genes, such as VEGFB and PGF, appeared completely absent in important vertebrate clades such as birds and amphibia, respectively. In contrast, individual PDGF/VEGF gene duplications frequently occurred in fish on top of the known fish-specific whole-genome duplications. The lack of precise counterparts for human genes poses limitations but also offers opportunities for research using organisms that diverge considerably from humans.
Graphical abstract
Sources for the graphical abstract: 326 MYA and older [1]; 72–240 MYA [2]; 235–65 MYA [3]
Funder
Päivikki ja Sakari Sohlbergin Säätiö
Otto A. Malm Lahjoitusrahasto
Finnish National Agency for Education
Finnish Pharmaceutical Society
Novo Nordisk Fonden
Academy of Finland
Paulon Säätiö
Einar and Karin Stroem Foundation for Medical Research
University of Helsinki including Helsinki University Central Hospital
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Clinical Biochemistry,Physiology
Cited by
1 articles.
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