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New Model For Snake Venom Evolution
April Flowers for redOrbit.com – Your Universe Online
Genomic mapping has changed the way animals are labeled as venomous or not. For example, if an animal’s oral glands show expression of some of the 20 gene families associated with “venom toxins,” current thinking labels that species as venomous.
A new study, which was led by The University of Texas at Arlington and published in Molecular Biology and Evolution, challenges current practices with a new model of how snake venoms evolved. The findings are based on a comprehensive, comparative analysis of related gene families in tissue from different parts of the Burmese python.
UTA assistant professor of Biology Todd Castoe led the research team that found similar levels of these so-called toxic gene families in the python brain, liver, stomach and several other organs. The team, which included scientists from Colorado and the UK, believe their findings demonstrate a great deal about the function of venom genes before they evolve into venoms, as well as showing that just the expression of such genes related to the venom toxins in oral glands of snakes and lizards isn’t enough information to place a definitive label of venomous or not-venomous on a species.
“Research on venom is widespread because of its obvious importance to treating and understanding snakebite, as well as the potential of venoms to be used as drugs, but, up until now, everything was focused in the venom gland, where venom is produced before it is injected,” Castoe said in a statement. “There was no examination of what’s happening in other parts of the snake’s body. This is the first study to have used the genome to look at the rest of that picture.”
A better understanding of the evolution of venom could aid scientists in developing more efficient anti-venoms, as well as add to the knowledge base concerning gene evolution in humans.
As genetic analysis capabilities increase, researchers are finding more evidence for a long-held theory which says that highly toxic venom proteins were evolutionarily “born” from non-toxic genes. These non-toxic genes have other, more ordinary, jobs in the body — for example, regulation of cellular function or digestion of food.
“These results demonstrate that genes or transcripts which were previously interpreted as ‘toxin genes’ are instead most likely housekeeping genes, involved in the more mundane maintenance of normal metabolism of many tissues,” said Stephen Mackessy, biology professor at the University of Northern Colorado. “Our results also suggest that instead of a single ancient origin, venom and venom-delivery systems most likely evolved independently in several distinct lineages of reptiles.”
In 2013, Castoe led a team of researchers who mapped the genome of the Burmese python (Python molurus bivittatus), which is not considered to be a venomous snake, despite having some of the same genes that have evolved into toxic venoms in other species. In highly venomous snake species, such as rattlesnakes or cobras, the venom gene families have expanded to make many copies of those shared genes, some of which evolved into genes that produce highly toxic venoms.
“The non-venomous python diverged from the snake evolutionary tree prior to this massive expansion and re-working of venom gene families. Therefore, the python represents a window into what a snake looked like before venom evolved,” Castoe said. “Studying it helps to paint a picture of how these gene families present in many vertebrates, including humans, evolved into deadly toxin encoding genes.”
For their analysis, the researchers examined 24 gene families associated with venom that are shared by pythons, cobras, rattlesnakes and Gila monsters. Traditional thinking on venom evolution holds that a core venom system developed at one point in the evolution of snakes and lizards. This point is called the Toxicofera, with many scientists believing that the evolution of highly venomous snakes, called caenophidian snakes, occurred afterward. Castoe and his team found, however, that this theory did little to explain why evolution would have picked just 24 genes to make into highly toxic venom-encoding genes, from the 25,000 or more possible.
“We believe that this work will provide an important baseline for future studies by venom researchers to better understand the processes that resulted in the mixture of toxic molecules that we observe in venom, and to define which molecules are of greatest importance for killing prey and causing pathology in human snakebite victims,” said Nicholas Casewell of the Liverpool School of Tropical Medicine.
Examining the python showed the team several common characteristics among the venom-related gene families that differentiated them from other genes. Castoe said that when the venom gene families are compared to other gene families in the python, they are “expressed at lower levels overall, expressed at moderate-high levels in fewer tissues and show among the highest variation in expression level across tissues.”
“Evolution seems to have chosen what genes to evolve into venoms based on where they were expressed (or turned on), and at what levels they were expressed,” Castoe continued.
The researchers developed a new model with three steps for venom evolution. The first step shows that the potentially venomous genes end up in the oral gland by default, because of their low, but consistent expression throughout the body. Second, natural selection on this expression in the oral gland is beneficial, which forces higher expression in the mouth than in other parts of the body. Third, as the venom evolves to become more toxic, the expression of these genes becomes limited in other organs to decrease the potential for the harmful effects of secreting such toxins in other areas of the body.
This new model is called the Stepwise Intermediate Nearly Neutral Evolutionary Recruitment, or SINNER. The researchers believe that differing levels of venom in snakes and other animals could be traced to the variability of where different species, or even different genes in within a single species, are along the continuum between the beginning and the end of the SINNER model.
To see if the SINNER model bears out, Castoe and his team would like to examine the genome of highly venomous snakes, next. The team hopes that the current findings, however, will change some of the thinking on which species are labeled as venomous, and which are not.
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Source: http://www.redorbit.com/news/science/1113295244/new-model-for-snake-venom-evolution-120914/
