OMG: T. rex did not have VEGF-B!

Wed, 05 Apr 2023 00:00:00 +0000

Our work on the evolutionary origin of the PDGF and VEGF growth factors has 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 makes intuitive sense (and had been proposed before by Jörg Wilting), 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:

The evolution of PDGF/VEGF growth factors

Thu, 22 Sep 2022 00:00:00 +0000

We have uploaded a preprint of our most recent manuscript about the evolution of PDGF/VEGF growth factors to bioRxiv. We comprehensively analyzed the PDGF/VEGF part of the proteome in all animal species for which data is available. We have had some of this data already for a while, but now we enhance it with a detailed look at fishes. The vascular biology of fishes has become even more facinating after the publication of Das et al. earlier this year ( read more about this exceptional piece of work ).The remarkable heterogeneity of vascular systems in fishes seems to be supported by a similar extensive heterogeneity at the molecular level. Often, but not always can this genetic heterogeneity be traced back to whole genome duplications. Fishes tolerate full genome duplications better than mammals. At least there have been quite a few such duplications in various branches of the fish phylogenetic tree resulting in polyploid or even tetraploid species. That has resulted in some fish species featuring 4 times as many PDGF/VEGF genes compared to humans, and much more opportunities to diversify the functions of these molecules.The very first PDGF/VEGF-like molecule appeared likely more than 800 Million years ago during the Precambrian period when marine organisms started to show signs of tissue organization. If we set out to reconstruct this molecule, it would look remarkably similar to a modern VEGF-C. Specifically the C-terminal “silk homology domain” seems to have been invented early on in evolution. In fact, a large number of extant morphologically simple organisms feature such VEGF-C-like molecules still today (e.g. the nematode C. elegans). Beyond these insights into the evolution of PDGFs and VEGFs, there are some useful take-home messages for vascular biologists: For example, we did not find any functional VEGF-B genes in birds. Similarly, there seem to be no PlGFs in amphibians. Then, on the other hand, the VEGF-Fs - identified from snake venoms - appear to exist more broadly also in non-venomous lizards. This poses some limitations on some animal models (Xenopus, CAM assay), but it would be nice to know what VEGF-F is doing in geckos…Have a look at the manuscript and please comment or criticize, if you have any thoughts! The idea is to make this manuscript still a bit better before submitting it to a journal for the traditional peer-review.

PDGF on Michael’s Domain

OMG: T. rex did not have VEGF-B!

The evolution of PDGF/VEGF growth factors