A team led by researchers at the Butantan Institute and funded by the São Paulo Research Foundation-FAPESP has completed the first genome sequencing of a snake in Brazil. The study was reported in an article published in the journal PNAS. This suggests that the nine genes that encode the toxins produced by the jararaca pit viper The samerops jararaca may have been derived from genes that had different functions in the ancestral species.
“In sequencing the snake genome, we identified markers that allow us to compare venom genes with genes that have the same position in the genomes of other animals, such as snakes without venom, lizards and amphibians.We found nine of the 1
2 venomous genes in Jararaca to be quite similar to those occupying the same position in the DNA of other species.We concluded that most of the venomous genes may have appeared from elements that already exist in the same part of the ancestral genome that are common to all of these animals, ”said Inácio Junqueira de Azevedo, a researcher at the Butantan Institute and final author of the article.
Azevedo is a chief investigator at the Center for Research on Toxins, Immune Response and Cell Signaling (CeTICS), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP.
“These genes have physiological functions in the common ancestor of all these species. At some point they are likely to have started to perform similarly to the genes that were poisonous or selected for this route and lost their original roles.Our study found elements that will help scientists understand the evolution of toxins and the mechanisms that led to the recruitment of certain genes to perform this new function in producing toxins, said Diego Dantas Almeida, first author of the article. The study was conducted during his Ph.D. research, supported by FAPESP.
The sequence also showed that the two genes that encode important toxins may have been derived from duplication. In any organism, a gene usually changes freely and ends up performing various functions when a copy has performed its original functions.
In jararaca, copies must be subjected to pressure to produce two families of toxins that account for most of the toxin action: ascending toxic metalloproteinases (SVMPs) and phospholipases A2 (PLA2). Most of the genes that encode these snake venom are thought to have originated this way. It is impossible to determine the origin of only one of the 12 families of genes that encode toxins.
“We’ve shown that non-toxic ‘ancestral’ genes exist in these two families. They’re still present in the DNA, right next to the toxic ones. The ancestral genes have completely disappeared from other families. Probably altered to poison poisons, “said Vincent Louis Viala, a co-author of the article and former recipient of a postdoctoral fellowship from FAPESP.
The Butantan Institute team began sequencing the genome of this snake in 2013. B. jararaca is responsible for a large proportion of snake bite accidents in Brazil and is one of the most studied snakes for this reason. The sequence produced basic information about the sources of its venom that they have lacked to this day.
In addition to enhancing the knowledge of genes in an organism, the sequence of its genome brings them together in the correct order. This is one of the most complex parts of the task because the sequence generates a vast amount of data, which needs to be processed using computational tools.
Only in recent years, after combining several methods, has the team succeeded in assembling the genome satisfactorily, in collaboration with researchers at Ohio State University in the United States. The complete genome sequence is available online to anyone who wants to study it.
The project produced answers to many other key questions. In 2009, a review by Japanese researchers of several toxin genes from Protobothrops flavoviridis, which belongs to the same family as jararaca (Viperidae), suggested a gene encoding the toxin VEGF-F, which is also present. in snakes in Brazil, which may be caused from duplication of the VEGF-A gene. The Brazilian group has now shown that it is more likely to come from another gene family known in the scientific literature as “like PGF”.
The team also gathered much evidence that the bradykinin-potentiating peptides (BPP), which is the basis for the anti-hypertensive drug captopril, may be derived from the CNP gene, which encodes the C-type natryuretic peptides present. in other vertebrates, including humans.
“The study illustrates the need to identify the context in which genes are inserted in order to correctly understand their origin and evolution,” Azevedo said.
Researchers are now working on finer versions of the genome of jararaca and other venomous snake families, hoping to find novel venoms and link them to proteins related to the physiology of other organism.
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Diego Dantas Almeida et al, Monitoring the recruitment and evolution of snake toxins using the evolutionary context provided by the bothrops jararaca genome, Proceedings of the National Academy of Science (2021). DOI: 10.1073 / pnas.2015159118