Four-legged fossil snake is a world first

The first four-legged fossil snake ever found is forcing scientists to rethink how snakes evolved from lizards. Although it has four legs, Tetrapodophis amplectus has other features that clearly mark it as a snake, says Nick Longrich, a palaeontologist at the University of Bath, UK, and one of the authors of a paper describing the animal in Science.

The creature’s limbs were probably not used for locomotion, the researchers say, but rather for grasping prey, or perhaps for holding on to mating partners. Such speculation inspired the snake’s name, which loosely translates as ‘four-legged hugging snake’. Tetrapodophis was originally found in the fossil-rich Crato Formation in northeastern Brazil several decades ago. But its legs can be difficult to see at first glance, and it languished in a private collection after its discovery, assumed to be unremarkable.

“I was confident it might be a snake,” says David Martill, a palaeobiologist at the University of Portsmouth, UK, who came across the find in 2012. “It was only after getting the specimen under the microscope and looking at it in detail that my confidence grew. We had gone to see Archaeopteryx, the missing link between birds and dinosaurs, and discovered Tetrapodophis, the missing link between snakes and lizards.”

Scientists have long argued over whether snakes evolved from land or marine animals. Tetrapodophis lacks adaptations for marine life, such as a tail useful for swimming. But its skull and body proportions are consistent with adaptations for burrowing. Longrich says that the finding unequivocally shows that snakes originated in the Southern Hemisphere and strongly supports a terrestrial origin.

Another striking feature of the fossil is its relative length. Tetrapodophis has 272 vertebrae, 160 of which are in its main body, not its tail. This number is more than twice the limit that researchers thought elongated bodies could reach before starting to lose their limbs.

Martin Cohn, an evolutionary developmental biologist at the University of Florida, Gainesville, says that the animal’s limbs must have been repurposed by evolution instead of simply dwindling away as its body became longer. This insight contradicts some assumptions about snake evolution. As Cohn explains, the paradigm about elongation of the trunk leading to limb loss now has to be adjusted. “This fossil shows that the two processes can be decoupled,” he says.

The discovery comes in a major year for snake evolution research, Cohn says. In January, the snake fossil record was pushed back by some 70 million years to the Middle Jurassic, around 160 million years ago, with the report of the oldest snake ever found. Although Tetrapodophis is not the oldest snake, Cohn says, “from a developmental perspective, this could be one of the most important fossils ever found. The combination of a snake-like body with complete forelimbs and hindlimbs is like a snake version of Archaeopteryx.”

Nature doi:10.1038/nature.2015.18050 Nature Original web page at Nature


* Some vaccines support evolution of more-virulent viruses

Scientific experiments with the herpesvirus such as the one that causes Marek’s disease in poultry have confirmed, for the first time, the highly controversial theory that some vaccines could allow more-virulent versions of a virus to survive, putting unvaccinated individuals at greater risk of severe illness. The research has important implications for food-chain security and food-chain economics, as well as for other diseases that affect humans and agricultural animals.

“The challenge for the future is to identify other vaccines that also might allow more-virulent versions of a virus to survive and possibly to become even more harmful,” said Andrew Read, an author of the paper describing the research, which will be published in the July 27, 2015 issue of the scientific journal PLoS Biology. Read is the Evan Pugh Professor of Biology and Entomology and Eberly Professor in Biotechnology at Penn State University.

“When a vaccine works perfectly, as do the childhood vaccines for smallpox, polio, mumps, rubella, and measles, it prevents vaccinated individuals from being sickened by the disease, and it also prevents them from transmitting the virus to others,” Read said. These vaccines are a type that is “perfect” because they are designed to mimic the perfect immunity that humans naturally develop after having survived one of these diseases. “Our research demonstrates that another vaccine type allows extremely virulent forms of a virus to survive — like the one for Marek’s disease in poultry, against which the poultry industry is heavily reliant on vaccination for disease control,” said Venugopal Nair, who led the research team in the United Kingdom where the experimental work related to this study was carried out. Nair is the head of the Avian Viral Diseases program at the Pirbright Institute, which also hosts the OIE Reference Laboratory on Marek’s disease. “These vaccines also allow the virulent virus to continue evolving precisely because they allow the vaccinated individuals, and therefore themselves, to survive, Nair said.

Less-than-perfect vaccines create a ‘leaky’ barrier against the virus, so vaccinated individuals sometimes do get sick, but typically with less-virulent symptoms. Because the vaccinated individuals survive long enough to transmit the virus to others, the virus also is able to survive and to spread throughout a population. “In our tests of the leaky Marek’s-disease virus in groups of vaccinated and unvaccinated chickens, the unvaccinated died while those that were vaccinated survived and transmitted the virus to other birds left in contact with them,” Nair said. “Our research demonstrates that the use of leaky vaccines can promote the evolution of nastier ‘hot’ viral strains that put unvaccinated individuals at greater risk.”

The theory tested by the research team was highly controversial when it first was proposed over a decade ago. The team’s experiments now show, for the first time, that the modern leaky vaccines, widely used in the agricultural production of poultry, can have precisely the effect on evolution of more-virulent strains of the virus that the controversial theory predicted.

Marek’s disease used to be a minor disease that did not do much harm to chickens in the 1950s, but the virulence of the virus has evolved and today it even is capable of killing all the unvaccinated birds in poultry flocks, sometimes within 10 days. “Even though the Marek’s disease virus is much nastier now than it was in the 1950s, it is becoming increasingly rare and now it causes relatively minor problems in the poultry industry because almost every chicken in agricultural production worldwide is vaccinated against the disease,” Read said. If you can vaccinate all the individuals in a population against a virus, it does not matter if the virus has become super virulent so long as the vaccine continues to be effective.”

The virus for Marek’s disease is very virulent, but the virus causing avian influenza can be even worse. “The most-virulent strain of avian influenza now decimating poultry flocks worldwide can kill unvaccinated birds in just under three days,” Read said. The vaccine against avian influenza is a leaky vaccine, according to Read. “In the United States and Europe, the birds that get avian influenza are culled, so no further evolution of the virus is possible,” Read said. “But instead of controlling the disease by culling infected birds, farmers in Southeast Asia use vaccines that leak — so evolution of the avian influenza virus toward greater virulence could happen.”

The research has implications for human health, as well. The World Health Organization recently reported laboratory-confirmed cases in China of human infection with the avian influenza virus, including a number of deaths. “We humans never have experienced any contagious disease that kills as many unvaccinated hosts as these poultry viruses can, but we now are entering an era when we are starting to develop next-generation vaccines that are leaky because they are for diseases that do not do a good job of producing strong natural immunity — diseases like HIV and malaria,” Read said.

“Vaccines for human diseases are the least-expensive, most-effective public-health interventions we ever have had,” Read said. “But the concern now is about the next-generation vaccines. If the next-generation vaccines are leaky, they could drive the evolution of more-virulent strains of the virus.” He said it is critical now to determine as quickly as possible that the Ebola vaccines that now are in clinical trials are not leaky — that they completely prevent the transmission of the Ebola virus among people. “We do not want the evolution of viral diseases as deadly as Ebola evolving in the direction that our research has demonstrated is possible with less-than-perfect, leaky vaccines,” Read said.

The researchers recommend rigorous testing and vigilant monitoring of next-generation vaccines to prevent the runaway evolution of more-virulent strains of viruses that their research has confirmed can occur with leaky vaccines. “If some day we have a malaria vaccine or an HIV vaccine, of course we should use those vaccines, but we would be in significant danger if those vaccines turned out to be leaky and we had not developed effective ways to eradicate any strains that might become more virulent,” Read said.

Read also recommends vaccination for individual protection. “When evolution toward more-virulent virus strains takes place as a result of vaccination practices, it is the unvaccinated individuals who are at the greatest risk. Those who are not vaccinated will be exposed, without any protection, to the hottest strains of a virus. Our research provides strong evidence for the importance of getting vaccinated.” Science Daily Original we page at Science Daily


Why is a dolphin not a cat?

A study of gene regulation in 20 mammals provides new insights into how species diverged millions of years ago. The findings demonstrate how methods and tools for genetic analysis of humans and mice can be adapted to study non-model species, such as whales and Tasmanian devils. New research shows how evolution has given rise to a rich diversity of species by repurposing functional elements shared by all mammals. Published in Cell by scientists at the European Bioinformatics Institute (EMBL-EBI) and the University of Cambridge Cancer Research UK-Cambridge Institute (CRUK CI), the study demonstrates how methods for understanding human biology can be used to understand a broad range of species.

Mammals all share a common ancestor, and they share a lot of the same genes. So what exactly makes a dolphin not a cat, and how did we all start to diverge from one another millions of years ago? Part of the answer lies in how — and when — genes are regulated. This latest research explores the evolution of gene regulation in 20 mammalian species, and provides deep insights into the ‘mammalian radiation’, a time of rapid morphological evolution that occurred shortly after the asteroid impact that caused the extinction of the dinosaurs.

Leveraging findings from a study comparing the genome sequences of 29 mammals, and with the help of conservation organisations such as the UK Cetacean Strandings Investigation Programme and the Copenhagen Zoo, the team were able to study and compare gene regulation in liver cells from 20 key species including the naked mole rat, human, Tasmanian devil, dolphin and sei whale.

“What we’ve shown is that evolution repurposes things that exist in all species, to make each species unique,” explains Paul Flicek, head of Vertebrate Genomics at EMBL-EBI. “By looking at gene promoters and enhancers in many different mammals, we demonstrated that species-specific enhancers come from ancient DNA — that evolution captures DNA that’s been around for a long time, and uses it for gene regulation in specific tissues.”

Evolution has two ways to turn changes in the genome into differences between species: it can change a protein sequence, or it can change the way promoters or enhancers control that protein’s expression. Today’s study also shows that in some cases evolution uses both strategies at once. When amino acid sequences evolve very quickly, important regulation changes occur at the same time: the protein-coding sequence and the corresponding regulatory sequence change synergistically.

Gathering the samples — the experimental efforts were led by Diego Villar of CRUK CI — took well over two years, and the experiments themselves produced a staggering volume of data. Analysing the results brought the team to a new frontier in bioinformatics. “People spend a lot of time and money trying to understand human biology, so most of the tools we have are designed to study human genomes,” explains Camille Berthelot of EMBL-EBI, who led the computational work. “The reference data we have for the less studied species, like the Sei whale or Tasmanian devil, are nothing like the pored-over datasets we have for the human genome. A lot of what we did involved benchmarking, and making sure the methods and algorithms were fit for this kind of comparison.”

“What inspired this work was a desire to get on top of the mountain, look out and see what is going on in the landscape of molecular evolution across the breadth of mammalian space,” says Duncan Odom of CRUK CI and Wellcome Trust Sanger Institute. “What’s exciting about this study is that we now know we can start to answer questions about the functional genetics of many under-explored species — questions we usually can ask only of humans and mice. We can use tools developed to study humans to understand the biology of all kinds of animals, whether they’re blackbirds or elephants, and explore their relationship with one another. This research has given us new insights into mammalian evolution, and proven how powerful these methods can be.”  Science Daily  Original web page at Science Daily