We are working on Vascular Endothelial Growth Factors. They are interesting therapeutic targets for diseases involving the vasculature, which includes almost all diseases (cardiovascular diseases, cancer, vascular dementia, etc.). There are five different VEGF genes in the human genome, but what about other animals? Nobody had systematically tried to answer this question before, so we just did!
The results of our work have just been published in Angiogenesis: https://doi.org/10.1007/s10456-023-09874-9. We analyzed both PDGFs and VEGFs, but our focus was naturally on the VEGF side of things. It's just a coincidence that the PDGFs happened to be a subgroup of the VEGFs and not vice versa, but that's of course just our biased point of view :-)
Since we do lymphatic research, we can proudly announce that the phylogenetic oldest VEGF likely resembled VEGF-C and featured the enigmatic silk homology domain. It also makes intuitive sense because the most simple vascular systems that we know of are the so-called hemolymph systems (e.g., in insects), which share many features with the lymphatic system.
With this publication, we did not do something exceptional that only a few can do. We did something everybody could do, but nobody had done so far: looking systematically at which animals have which PDGFs and VEGFs. Actually, we did something new: we developed a crowdsourcing method for classifying PDGFs and VEGFs. Instead of asking people, we asked databases. There are many PDGF-like and VEGF-like sequences in databases, which are only recognizable as such by the homology of their amino acid sequence. In order to know whether we are dealing, e.g., with a VEGF-C or a VEGF-D, we are running many (PSI)BLAST searches, and then we tally up the majority opinion (as determined by the top hits).
Many surprises waited for us after the bioinformatics script had finished its job after two weeks of finding and comparing PDGF- and VEGF-like sequences:
<li>Birds and crocodiles don't have VEGF-B (despite some avian VEGFs being wrongly labeled "VEGF-B" in the databases).</li>
<li>As a consequence of the above, T-rex and Triceratops very likely did not have any VEGF-B genes either.</li>
<li>In amphibians, we did not find any PlGF.</li>
<li>VEGF-F is not only a snake venom component but has likely been only co-opted for that purpose recently. VEGF-F is present in non-venomous reptiles, but nobody knows its function.</li>
<li>VEGF-E-containing viruses (Orf virus, etc.) do not only infect mammals, but there are VEGF-E-containing viruses that infect fish!</li>
<li>Many fishes have more than one VEGF-C gene, but not due to the teleost genome duplication.</li>
Intriguing? If yes, head over to Angiogenesis and download your copy! For a bioinformatics paper, it is a bit on the long side, but we wanted to be comprehensive. Since we constantly sequence more and more animal genomes, the actual data of the manuscript is constantly changing, and I am working on a way how to automatically update the online version of the data...