Proposal for a new universal nomenclature for oxytocin and vasotocin genes
Oxytocin and arginine vasopressin are two hormones in the endocrine system that can act as neurotransmitters and regulate – in vertebrates and invertebrates – a wide range of biological functions, such as bonding, lactation, birth or blood pressure. Pre-genomic-era biochemists named these genes differently in different species, due to small differences in protein coding.
A new study by the University of Barcelona (UB) and Rockefeller University, published in the journal Nature, analyzed and compared the genome of 35 species representing all lineages of vertebrates and came to the conclusion that the two hormones come from a common ancestral gene.
These high quality genomes were obtained through the use of innovative genome sequencing technologies as part of the Vertebrate Genomes project. Based on these results, the researchers propose a new universal nomenclature, based on their identified evolutionary history for these genes. According to the study authors, the proposal allows for a new universal nomenclature among vertebrates, both for hormonal genes and for their receptors, thus facilitating comparative research between species.
The article is part of the doctoral thesis of Constantina Theofanopoulou, carried out at UB under the co-supervision of Cedric Boeckx, ICREA researcher at the Institute of Complex Systems at UB (UBICS) and Erich D. Jarvis, professor at Rockefeller University.
Terminological confusion between species
The study results from problems that the first author of the study, Constantina Theofanopoulou, became aware of in the literature of these genes, by analyzing the role of oxytocin in the vocal learning capacity of songbirds. “When analyzing the scientific literature for previous work on this gene, we observed that when talking about birds, scientists used the term ‘mesotocin’ instead of ‘oxytocin’. other vertebrate species, such as turtles, frogs or fish. An equally confusing nomenclature was that used for their respective receptors, which made it very difficult to understand which gene is which in different species and lineages, ”explains Constantina Theofanopoulou. Against this background, the researchers set out to find out which genes were truly orthologous to each other in different species. To do this, they used genome assemblies generated by the Vertebrates Genome Project, an international collaboration led by Erich Jarvis of Rockefeller University. In a first phase, Theofanopoulou and the research team compared the genomes and more precisely the order of genes around their genes of interest. They studied up to sixty genes around the genes of interest, as well as all the genes on the chromosomes where these genes are located. They investigated whether the order of genes – called synteny – was conserved across species, which would shed light on the evolutionary history of these genes.
The new high quality assemblies have been more than helpful because, as Theofanopoulou says, “most genomes so far have been of poor quality, which means millions of errors, parts of genes missing or poorly assembled. . These errors can have direct consequences for scientific discoveries. “.
Genes with a common ancestor
The results, along with other phylogenetic analyzes performed during the study, show that the genes that the researchers in this study now call oxytocin and vasotocin – which encode the homonymous hormones – are paralogous, that is, that is, they come from a local duplication of a common ancestral gene. “Our results suggest that the oxytocin gene is a duplication of the vasotocin gene – historically called vasopressin – that occurred after vertebrate jaw divergence from jawless vertebrates. This simultaneously means that, if we had understood the evolution of these genes from the very beginning, we probably would not have used different names to refer to them, as we see in other gene families, where we let’s use the same root name for all its genetic members (eg FOXP) and different numbers to differentiate them (eg FOXP1, FOXP2 etc.) “, emphasizes Constantina Theofanopoulou.
Based on the results, the researchers propose a universal nomenclature in which oxytocin and vasotocin are used for these genes in all jaw vertebrates, and vasotocin for the single gene presents all jawless vertebrates and closely related invertebrates. In this proposal, the common origin of the two genes would be represented by the shared suffix -tocin, while the parology would be displayed by the different prefixes (oxy- and ¬vaso-). According to this proposed new nomenclature, what is currently called oxytocin, mesotocin, isotocin, glumitocin, valitocin, aspargtocin and neurophysin in different lineages, would henceforth be universally called oxytocin. As for what is currently called vasotocin, vasopressin, neurophysin 2 and phenypresin in different species would henceforth be called vasotocin for all species.
This proposal also includes a universal nomenclature for the receptors of the two genes, namely the receptors for oxytocin and vasotocin (OTR and VTR). Therefore, what has traditionally been called the oxytocin receptor (OXTR) in mammals, the vasotocin 3 receptor (VT3) and the mesotocin receptor (MTR) in birds and frogs, and the isotocin receptor (ITR) in fish, would henceforth be called oxytocin receptor (OTR). in all cases.
Evolutionary history of oxytocin and vasotocin
The study also identified six major receptors for oxytocin and vasotocin in vertebrate jaws, two of them already present in hagfish, two more in lampreys, which have four receptors in total, and two more. in the jaw, which display six receptors in total. . This model suggests that these receptors first evolved through a cycle of whole-genome duplication that gave rise to the four receptors that we find in jawless vertebrates, such as lampreys, and that subsequently, either segmental duplications. on a smaller scale, another whole genome duplication gave rise to the six receptors in vertebrate jaws.
This is the second time that researchers have found evidence of a scenario with one round of whole genome duplication, instead of two. The hypothesis that vertebrate genomes evolved over two rounds of whole genome duplication has not been contested for nearly fifty years. “Our data show more support for the single-cycle idea of whole genome duplication. If the two rounds of whole-genome duplication were the case, we would expect to find eight receptors in total and not six receptors in vertebrate jaws. Of course, gene loss is very common, which is why we cannot rule out a two-round scenario, but we did not find any genomic evidence of gene loss in any of the vertebrate jaw genomes that we studied ” , notes the researcher.
The next step would be to have this new nomenclature adopted, which is based on the evolutionary history of genes. “This is the first time that such a universal change affecting so many genes and species has been presented. Whether this proposal is adopted or not, researchers will now have a guide on genetic orthologies between species, which will lead their research much easier, ”concludes Constantina Theofanopoulou.