How lizards regenerate their tails: researchers discover genetic 'recipe'


August 20, 2014

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic “recipe” for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.

An interdisciplinary team of scientists used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration. The team studied the regenerating tail of the green anole lizard (Anolis carolinensis), which, when caught by a predator, can lose its tail and then grow it back. green anole lizard (Anolis carolinensis) Download Full Image

The findings are published today in the journal PLOS ONE.

"Lizards basically share the same toolbox of genes as humans," said lead author Kenro Kusumi, professor in ASU's School of Life Sciences and associate dean in the College of Liberal Arts and Sciences. "Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing.”

Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the 'Wnt pathway’ – a process that is required to control stem cells in many organs, such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.

"Regeneration is not an instant process," said Elizabeth Hutchins, a graduate student in ASU's molecular and cellular biology program and co-author of the paper. "In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail.”

"We have identified one type of cell that is important for tissue regeneration," said Jeanne Wilson-Rawls, co-author and associate professor with ASU’s School of Life Sciences. "Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues."

"Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail," said Kusumi. "By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future."

The researchers hope their findings will help lead to discoveries of new therapeutic approaches to spinal cord injuries, repairing birth defects and treating diseases such as arthritis.

The research team included Kusumi, Hutchins, Wilson-Rawls and Alan Rawls, as well as Dale DeNardo from ASU School of Life Sciences; Rebecca Fisher from ASU School of Life Sciences and the University of Arizona College of Medicine Phoenix; Matthew Huentelman from the Translational Genomic Research Institute; and Juli Wade from Michigan State University. This research was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission.

ASU’s School of Life Sciences is an academic unit of the College of Liberal Arts and Sciences.

Sandra Leander

Manager, Media Relations and Marketing, School of Life Sciences

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New research shows seals, sea lions likely spread tuberculosis to humans


August 20, 2014

Tuberculosis is one of the most persistent and deadliest infectious diseases in the world, killing one to two million people each year.

Scientists who study tuberculosis have long debated its origins. New research shows that tuberculosis likely spread from humans in Africa to seals and sea lions that brought the disease to South America and transmitted it to Native people there before Europeans landed on the continent. sea lion from Peru Download Full Image

The paper, “Pre-Columbian Mycobacterial Genomes Reveal Seals as a Source of New World Human Tuberculosis,” was published in Nature.

“We found that the tuberculosis strains were most closely related to strains in pinnipeds, which are seals and sea lions,” said researcher Anne Stone, Arizona State University School of Human Evolution and Social Change professor. Stone and Johannes Krause of the University of Tubingen in Germany are co-principal investigators on the project. Research teams from the Wellcome Trust Sanger Institute in the United Kingdom and the Swiss Institute for Tropical and Public Health were collaborators on the study.

“What we found was really surprising. The ancient strains are distinct from any known human-adapted tuberculosis strain,” Stone added.

Modern strains of tuberculosis currently circulating are most closely related to those found in Europe, and there was a complete replacement of the older strains when European disease reached the Americas during the age of exploration. Researchers found that genomes from humans in Peru dating from about 1,000 years ago provide unequivocal evidence that a member of the tuberculosis strain caused disease in South America before Europeans arrived, so the question among the scientists was, “What types of tuberculosis strains were present before contact?”

“The age of exploration is a time when people are moving really long distances around the world and coming into contact with others. It’s a time when a lot of disease spread,” Stone said. “This opens up a lot of new questions. It fits the bioarcheological evidence that shows the oldest evidence for tuberculosis in South America.”

“The connection to seals and sea lions is important to explain how a mammalian-adapted pathogen that evolved in Africa around 6,000 years ago could have reached Peru 5,000 years later,” Krause said.

In the study, researchers collected genetic samples from throughout the world and tested those for tuberculosis DNA while utilizing advances in technology during the past five years that enable more accurate genome capture from ancient samples. Of 76 DNA samples from New World pre- and post-contact sites, three from Peru around 750-1350 A.D. had tuberculosis DNA that could be used. The researchers then focused on these three samples and used array-based capture to obtain and map the complete genome.

These were compared against a larger dataset of modern genomes and animal strains. Research results showed the clear relationship to animal lineages, specifically seals and sea lions.

“Our results show unequivocal evidence of human infection caused by pinnipeds (sea lions and seals) in pre-Columbian South America. Within the past 2,500 years, the marine animals likely contracted the disease from an African host species and carried it across the ocean to coastal people in South America,” Stone said.

Africa has the most diversity among tuberculosis strains, implying that the pathogen likely originated from the continent and spread. After tuberculosis was established in South America, it may have moved north and infected people in North America before European settlers brought new strains in.

“We hypothesize that when the more virulent European strains came, they quickly replaced the pinniped strains,” Stone said.

“It was a surprise for all of us to find that tuberculosis, formerly believed to have spread around the world with ancient human migration events, is in fact a relatively young disease," said Kelly Harkins, one of the study's first authors and a recent doctoral graduate from ASU's Center for Bioarchaeological Research.

“A compelling prospect for future research will be to determine the relationship of these older forms to those currently circulating, and those isolated from other ancient remains,” said Kirsten Bos, a postdoctoral fellow at the University of Tuebingen and another first author on the study.

Study implications include a greater understanding of the speed and process of adaptation when a disease changes hosts. This is especially of interest when considering diseases that are transmitted between species – MERS, SARS and HIV – and how these are spread, Stone added.

“Tuberculosis is a disease that is on the rise again, worldwide. This study and further research will help us understand how the disease is transmitted and how the disease may evolve,” said Jane Buikstra, a collaborator on the study who identified tuberculosis in most of the cases utilized in the research. Buikstra is an ASU Regents' Professor and director of the Center for Bioarchaeological Research.