Texas A&M researcher collaborates on work that reveals clues to cat domestication

COLLEGE STATION, Texas – Cats and humans have shared the same households for at least 9,000 years, but we still know very little about how our feline friends became domesticated. An analysis of the cat genome led by researchers at Washington University School of Medicine, and that included a Texas A&M University professor, reveals some surprising clues.

The research article appears in the current issue of the Proceedings of the National Academy of Sciences Early Edition.

Cats have a relatively recent history of domestication compared with dogs; canines arose from wolves over 30,000 years ago.

“Cats, unlike dogs, are really only semi-domesticated,” said senior author Wes Warren, PhD, associate professor of genetics at The Genome Institute at Washington University in St. Louis. “They only recently split off from wild cats, and some even still breed with their wild relatives. So we were surprised to find DNA evidence of their domestication.”

One way scientists can understand the genetics of domestication is to look at what parts of the genome are altered in response to living together with humans, Warren added.

The researchers compared the genomes of domestic cats and wild cats, finding specific regions of the domestic cat genome that differed significantly.

The scientists found changes in the domestic cat’s genes that other studies have shown are involved in behaviors such as memory, fear and reward-seeking. These types of behaviors-particularly those when an animal seeks a reward-generally are thought to be important in the domestication process.

“Humans most likely welcomed cats because they controlled rodents that consumed their grain harvests,” said Warren. “We hypothesized that humans would offer cats food as a reward to stick around.”

This meant that certain cats that would normally prefer to lead solitary lives in the wild had an additional incentive to stay with humans. Over time, humans preferred to keep cats that were more docile.

Cat genome project

The cat genome sequencing project, funded by the National Human Genome Research Institute, part of the National Institutes of Health (NIH), began in 2007. The project’s initial goal was to study hereditary diseases in domestic cats, which are similar in some cases to those that afflict humans, including neurological disorders, and infectious and metabolic diseases.

To obtain the high-quality reference genome needed for this research, the team sequenced a domestic female Abyssinian cat named Cinnamon. They chose this particular cat because they could trace its lineage back several generations. This cat’s family also had a particular degenerative eye disorder the researchers wanted to study.

To better understand characteristics of domestication, the researchers sequenced the genomes of select purebred domestic cats. Hallmarks of their domestication include features such as hair color, texture and patterns, as well as facial structure and how docile a cat is. Cats are bred for many of these types of characteristics. In fact, most modern breeds are the result of humans breeding cats for their favorite hair patterns.

The team also looked at a breed called Birman, which has characteristic white paws. The researchers traced the white pattern to just two small changes in a gene associated with hair color. They found that this genetic signature appears in all Birmans, likely showing that humans selectively bred these cats for their white paws and that the change to their genome happened in a remarkably short period of time.

The group also compared the cat genome with those of other mammals – including a tiger, cow, dog and human – to understand more about the genetics of cat biology.

“We looked at the underlying genetics to understand why certain abilities to survive in the wild evolved in cats and other carnivores,” said Michael Montague, PhD, the study’s first author and a postdoctoral research associate at The Genome Institute.

The differences they found in the cat genome help explain characteristics such as why cats are almost exclusively carnivorous and how their vision and sense of smell differ from other animals like dogs.

“Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) researchers such as Dr. William Murphy have long been interested in investigating the cat genome,” said Dr. Evelyn Tiffany-Castiglioni, department head for Veterinary Integrative Biosciences at the CVM. “We have a wealth of expertise in genomics, and participating in collaborative efforts such as this are helping to unlock clues not only to the evolution of domestic and wild cats, but also how their interactions with humans and the environment have influenced their evolutionary development.”

Solitary carnivores

To digest their fatty, meat-heavy meals, cats need genes to efficiently break down fats. The team found particular fat-metabolizing genes in carnivores such as cats and tigers that changed faster than can be explained by chance. This more rapid change generally means these genes provide some sort of digestive advantage to carnivores that only consume animal proteins. The researchers did not find such changes in the same genes of the cow and human, who eat more varied diets and would not need such enhancements.

Cats also rely less on smell to hunt than dogs. So it is not surprising that the researchers found fewer genes for smell in cats than dogs. But they did find more genes related to an alternate form of smell that detects chemicals called pheromones, which allow cats to monitor their social environment, including seeking out the opposite sex. This ability is not as important to dogs, which tend to travel in packs. But it is crucial in cats, which are more solitary and may have more difficulty finding mates.

Cats also have better hearing than most other carnivores, including an ability to hear in the ultrasonic range to better track prey. Their vision is also exceptional in low light.

“Cats tend to be more active at dawn and dusk,” said Montague, “so they need to be able to detect movement in low light.” Accordingly, the team identified specific genes that likely evolved to expand cats’ hearing range and their vision in low light.

Even though the genomes of domestic cats have changed little since their split from wild cats, the new work shows that it is still possible to see evidence of the species’ more recent domestication. “Using advanced genome sequencing technology, we were able to shed light on the genetic signatures of cats’ unique biology and survival skills,” said Warren. “And we were able to significantly jump start our knowledge about the evolution of cat domestication.”

Other collaborators include University of Missouri-Columbia; University of California-Davis; Wellcome Trust Sanger Institute in the United Kingdom; Pompeu Fabra University in Spain; Centro de Analisis Genomico in Spain; Bilkent University in Turkey; Indiana University; Center for Cancer Research in Maryland; St. Petersburg State University in Russia; and Nova Southeastern University in Florida.

The research is funded by the National Human Genome Research Institute at the National Institutes of Health (NIH) (grant number U54HG0003079), the National Science Foundation (DBI-0845494), Morris Animal Foundation (D06FE-063 and D12FE-019), European Research Council starting grant (260372), the Spanish government (BFU2011-28549), National Center for Research Resources (R24RR016094 and R24 OD010928) and the Winn Feline Foundation (W10-014 and W09-009).

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Contact Information:

Megan Palsa, PhD
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College of Veterinary Medicine & Biomedical Sciences
Texas A&M University
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Texas A&M Dean To Serve On Task Force Studying Use Of Antibiotics In Production Agriculture

COLLEGE STATION, TX, Nov. 7, 2014 – Eleanor M. Green, The Carl B. King Dean of Veterinary Medicine, College of Veterinary Medicine & Biomedical Sciences at Texas A&M University has been appointed to a national task force that will advise the federal government on the use of antibiotics in production agriculture.

Jointly announced by the Association of Public and Land-Grant Universities (APLU) and the Association of American Veterinary Medical Colleges (AAVMC), the group will advise the government on a research agenda regarding the use of antibiotics in agriculture and will disseminate information on the issue.

“We recognize antibiotic resistance as a public health challenge and look forward to collaborating with APLU and the federal government on this critical initiative,” said AAVMC Executive Director Andrew T. Maccabe, noting that many of the AAVMC’s member institutions are based at land-grant universities.

The task force will draw upon the expertise of its members to provide advice to the federal government as they develop plans. The task force is comprised of representatives from U.S. agriculture colleges/land grant universities and veterinary colleges as well as key representatives from the production animal agriculture community and the pharmaceutical industry.

The goal of the task force will be to offer advice to the federal government on a research agenda and also help publicly disseminate information on the use of antibiotics in production agriculture.

“Antibiotic resistance is a growing national concern with far reaching implications in human medicine, veterinary medicine, and food safety and security,” said Green. “This is a unique opportunity to identify solutions systematically, comprehensively, and innovatively with the goal of positively impacting animal health and human health using a One Health approach that brings together multiple disciplines and entities. This task force does that. I look forward to working with such a diverse group of distinguished scientists, practitioners, and industry representatives to develop recommendations for addressing antibiotic resistance and protect public health. It is an honor to represent the AAVMC, the national organization for academic veterinary medicine, and the College of Veterinary Medicine & Biomedical Sciences at Texas A&M University, a land grant institution.”

The President’s Council of Advisors on Science and Technology (PCAST) recently released a report, “Combating Antibiotic Resistance,” discussing several recommendations to address the problem. President Barack Obama also issued an executive order describing the problem as a national security priority and directing a few executive branch departments and agencies to develop a plan of action by February 2015 to address antibiotic resistance and protect public health.

Once policies are established, APLU institutions such as Texas A&M will work to educate producers and the public about the appropriate use of antibiotics in agriculture and veterinary medicine. “This is an important collaborative effort,” said Peter McPherson, president of the APLU, which is a research, policy and advocacy organization representing 237 public research universities, land-grant institutions, state university systems and affiliated organizations. “The task force and its members are well-positioned to advise the Obama administration as they consider strategies to address the judicious use of antibiotics in production agriculture.”

The Association of American Veterinary Medical Colleges is a nonprofit membership organization working to protect and improve the health and welfare of animals, people and the environment by advancing academic veterinary medicine.

In addition to Green, the task force members include Lonnie J. King, dean, Ohio State University College of Veterinary Medicine (chair); Robert A. Easter, president, University of Illinois (co-chair); Richard A. Carnevale, vice president of Regulatory, Scientific and International Affairs, Animal Health Institute; Thomas Coon, vice president, dean and director, Oklahoma State University Division of Agricultural Sciences and Natural Resources; Ronnie D. Green, IANR Harlan Vice Chancellor at the University of Nebraska-Lincoln and University of Nebraska vice president; Walter Hill, dean, College of Agriculture, Environment and Nutrition Sciences, Tuskegee University; Christine Hoang, assistant director, Division of Scientific Activities, American Veterinary Medical Association; Ashley Peterson, vice president of science and technology, National Chicken Council; Willie Reed, dean, College of Veterinary Medicine, Purdue University; Kathy Simmons, chief veterinarian, National Cattlemen’s Beef Association; and Liz Wagstrom, chief veterinarian, National Pork Producers Council. Officials from key federal agencies are expected to serve as observers and leaders from public universities in Mexico and Canada also will serve as ex officio members.

Researchers at Texas A&M Plan Interdisciplinary Chagas Disease Research Program

 

COLLEGE STATION, Texas – A Texas A&M University team of researchers plans to approach research on Chagas disease from an ecological perspective. They will look at how environmental factors, such as climate and land cover, and socioeconomic factors, such as housing conditions, affect the distribution of the disease. As the disease is primarily transmitted by insects called kissing bugs, any factor that influences kissing bug abundance or behavior will also impact disease risk. For example, poor housing conditions allow kissing bugs to colonize the home and increase the opportunity for them to take a blood meal from a sleeping human.  Furthermore, as the climate changes, the distribution of the kissing bugs can shift, which could lead to the emergence of Chagas disease in new areas of the United States.

Chagas disease, which affects approximately eight million people in the Americas, according to the United States Centers for Disease Control and Prevention, is caused by the parasite Trypanosoma cruzi and is spread by kissing bugs that are prevalent across North, Central, and South America. Although once thought to be only a tropical disease, there is a current problem of canine Chagas disease in many regions of Texas that affects working dogs (such as military or border patrol), prized purebred breeding and show dogs, household pets, and stray dogs. In addition to the humans and dogs affected, the disease has been reported in South America in both cattle and pigs, and thus has the potential to threaten the economic stability of those who rely on livestock. Between 30 and 40 percent of those infected will develop life-threatening heart disease.

In addition to the cardiac complications, humans can also experience intestinal complications and even-especially in young children-meningoencephalitis, which is a life-threating inflammation of the brain.

The team’s research proposal, chosen through a competitive process, is one of only four to receive funding through the Texas A&M One Health Grand Challenge. It is a collaboration of faculty members in six Texas A&M colleges: Gabriel Hamer at the College of Agriculture and Life Sciences, Cecilia Giusti at the College of Architecture, Dan Goldberg at the College of Geosciences, Charles Criscione at the College of Science, Sarah Hamer at the Veterinary Medicine & Biomedical Sciences (CVM), and Ann Millard at the School of Public Health at the Health Science Center. Together, they have expertise in ecology, epidemiology, population genetics, parasitology, community health, border health, medical anthropology, medical and veterinary entomology, land and economic development and planning, Latin American studies, and spatial analysis.

“Zoonotic diseases are the ultimate One Health challenge because of the complex interactions among humans, wildlife, domestic animals, vectors, and pathogens within shared environments,” said Dr. Sarah Hamer, an assistant professor in the College of Veterinary Medicine & Biomedical Sciences (CVM) and the principal investigator on the project. “We plan for our research and outreach on Chagas disease to serve as ‘proof of principle,’ and that our One Health approach will be extended to tackle other vector-borne zoonotic disease systems in the future. We are in a great place for Texas A&M University to be a leader in multidisciplinary vector-borne disease research.”

The team plans a three-pronged approach to their research in south Texas. First, they will trap kissing bugs, collect wildlife, domestic animal, and human blood samples, and assess the socioeconomic environment. Then, they will process samples in the laboratory to sequence DNA and determine the population genetics of both the parasites and the kissing bugs that transmit them. Finally, they will use that information to map the disease over time and space, taking into account the relationships between environmental, climatic, and demographic factors that influence spread and severity of disease. This map will then serve as a basis for future research, as it can help identify risk factors and evaluate intervention strategies.

“This research program represents well what the One Health Grand Challenge at Texas A&M University is all about,” said Dr. Eleanor M. Green, the Carl B. King Dean of Veterinary Medicine at the CVM. “Facilitated by Dr. Michael Chaddock, assistant dean for One Health, investigators came together from across campus to form the research team dedicated to finding extraordinary solutions for this disease of importance to Texas and beyond. Equally impressive is the funding of this project, which was also a team approach. Dr. Glen Laine, vice president for research at Texas A&M, matched voluntary contributions from the involved colleges to fully fund this challenge proposal.”

Although there is a recent increase in awareness of Chagas disease in Texas, researchers believe Chagas disease has existed in the Southern U.S. for a long time.  In fact, mummified remains of humans from Texas and South America who died more than 1,150 years ago have evidence of Chagas disease.

“This devastating disease is one of several neglected tropical diseases that can increase the poverty in already disadvantaged regions as it can have impacts on child development and worker productivity,” said Dr. Michael Chaddock. “As an under-diagnosed, under-reported disease with poorly-understood risk factors, this type of research is desperately needed.”

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About the Texas A&M One Health Initiative: The initiative is dedicated to the discovery, development, communication, and application of knowledge in a wide range of academic and professional fields providing the highest quality undergraduate, graduate and professional programs to prepare students to assume roles in leadership, responsibility and service to society. It builds on the strength of the university and the state of Texas from discovery to application and commercialization allowing for the discovery, learning and applied research to meet societal needs. Learn more about the One Health Initiative at http://onehealth.tamu.edu.

Han Leads Research Initiative Selected for One Health Grand Challenge

COLLEGE STATION, Texas – A research initiative lead by Dr. Arum Han from the Department of Electrical and Computer Engineering at Texas A&M University is one of the four university-wide initiatives selected for the One Health Grand Challenge.

The One Health Grand Challenge was offered as an opportunity for the Texas A&M schools and colleges to plan and implement a transdisciplinary, collaborative approach to help improve the lives of all species-humans and animals-by addressing health and their connections between natural and man-made environments.

The One Health Grand Challenge identified four major One Health research themes and implementing a plan to bring together teams to propose research initiatives under these themes.

Han’s team has faculty from the College of Veterinary Medicine & Biomedical Sciences (CVM), Dwight Look College of Engineering (ENG), Texas A&M Health Science Center (TAMHSC), and Texas A&M AgriLife. They included Jane Welsh (CVM), Allison C. Rice-Ficht (TAMHSC), Arul Jayaraman (ENG), Paul de Figueiredo (TAMHSC/AgriLife), Jianrong Li (CVM), Thomas Ficht (CVM), Robert C. Alaniz (TAMHSC), Byung-Jun Yoon (ENG), Michael Pishko (ENG), Michael Criscitiello (CVM), Garry Adams (CVM), Melissa Grunlan (ENG), Evelyn Tiffany-Castiglioni (CVM), Won-Bo Shim (AgriLife), Yoonsuck Choe (ENG), Michael Polymenis (AgriLife), Timothy P. Devarenne (AgriLife), and Wonmuck Hwang (ENG).

The title of their initiative is “Miniature Tissues and Organs for Detection and Prevention of Diseases,” and focuses on development of next-generation biologics through microphysiological systems. It was selected for the One Health Accessible & Affordable Quality Health Care theme.

“I believe that multidisciplinary collaboration is key in addressing challenges in this new One Health paradigm,” said Han, “and I hope that engineering technologies can make significant contributions towards solving these grand challenges of societal importance.”

The vision of this Microphysiological Systems initiative is to create a world where human, animal, and plant diseases can be readily detected, disease mechanisms can be accurately and quickly deciphered, emerging threats can be predicted, and new therapeutics and vaccines can be rapidly developed, all at low cost, thus ultimately providing accessible and affordable healthcare.

The technological innovations at the core of this initiative are in developing in vitro microsystems that closely mimic the physiology of whole organisms, and in developing lab-on-a-chip systems that are high throughput, accurate, flexible, and low cost. Systems that mimic (or reproduce) human physiological systems (e.g., organ-on-a-chip) aim to overcome the limitations of currently used in vitro models and animal models. Lab-on-a-chip systems can accelerate assays and significantly lower costs. Combined together, the team is hoping to provide a new paradigm for improving our capabilities to provide accessible and affordable healthcare. The initial focus areas of this initiative will be neurodegenerative diseases, immune systems, and the human microbiome; however, the team is hoping that the developed systems and their applications can be more broadly expanded and adapted to solving other health problems of high societal importance.

“The proposal submitted by Dr. Han and his team of investigators holds great promise in radically changing how we examine organ systems and perform diagnostics in multiple species,” said Dr. Michael Chaddock, assistant dean for One Health and Strategic Initiatives at the CVM. “Interdisciplinary approaches such as this-that advance knowledge, that will improve global health-is at the very core of the definition of One Health.”

The One Health Initiative was started at Texas A&M in 2011 to be a collaborative effort of multiple disciplines working locally, nationally, and globally to attain sustainable optimal health for the ecosystem. It’s driven by agents of change which include, but are not limited to, population growth; nutritional, agricultural and trade practices; globalization; shift in land use; accelerated urbanization; deforestation; encroachment on wildlife; and climate change.

“This research program represents well what the One Health Grand Challenge at Texas A&M University is all about,” said Dr. Eleanor M. Green, the Carl B. King Dean of Veterinary Medicine at the CVM. “Facilitated by Dr. Michael Chaddock, investigators came together from across campus to form the research team dedicated to finding extraordinary solutions for diseases of importance to Texas and beyond. Equally impressive is the funding of this project, which was also a team approach. Dr. Glen Laine, vice president for research at Texas A&M, matched voluntary contributions from the involved colleges to fully fund this challenge proposal.”

The initiative is dedicated to the discovery, development, communication, and application of knowledge in a wide range of academic and professional fields providing the highest quality undergraduate, graduate and professional programs to prepare students to assume roles in leadership, responsibility and service to society. It builds on the strength of the university and the state of Texas from discovery to application and commercialization allowing for the discovery, learning, and applied research to meet societal needs.

“We have a tremendous amount of expertise and human capital at Texas A&M and we are ideally suited to address many of society’s greatest health challenges,” said Dr. M. Katherine Banks, vice chancellor and dean of engineering. “Innovation thrives when we bring great scholars together and it is exciting to imagine the possible advances that will come from their multidisciplinary approach to problem solving.”

Obesity and Stress Research Addressed in One Health Grand Challenge Project

COLLEGE STATION, Texas – Enhancing the health and well-being of animals and humans through the alleviation of chronic illnesses and conditions is the goal of an innovative project recently awarded funding through the competitive One Health Grand Challenge proposal process. The project’s team will approach this objective by addressing the adverse physical, societal, and economic effects of these stressful, chronic conditions, including metabolic dysregulation and obesity.

The One Health Grand Challenge was offered as an opportunity for Texas A&M University faculty members to plan and implement a multi-disciplinary, collaborative approach improving the lives of all species-human and animal-by addressing health as well as the connections between health and both natural and man-made environments.

The One Health Grand Challenge faculty advisory committee identified four major One Health research themes and implemented a plan to bring together teams to propose research initiatives under these themes.

The interdisciplinary team includes faculty from the Texas A&M College of Agriculture & Life Sciences (COALS), Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), Texas A&M Health Science Center College of Medicine, Texas A&M AgriLife Research, Texas A&M Health Science Center College of Pharmacy, Texas A&M College of Liberal Arts, the Dwight Look College of Engineering (ENG), and the Texas A&M College of Education & Human Development (EDU). They included Tom Welsh, principal investigator (COALS, CVM, AgriLife Research), Robert Alaniz (TAMHSC), Gordon Carstens (COALS, AgriLife Research), Mahua Choudhury (TAMHSC-Kingsville), Noah Cohen (CVM), Kevin Curley (CVM), Sherecce Fields (Liberal Arts), Kianfar Kiavash (ENG), Narendra Kumar (TAMHSC-Kingsville), Sara Lawhon (CVM), John Lawler (EDU), Jeff Liew (EDU), Dai Lu (TAMHSC-Kingsville), Lisako McKyer (EDU), Mary Meagher (Liberal Arts), Cynthia Meininger (TAMHSC-Temple), Peter Murano (COALS), Dave Potter (TAMHSC-Kingsville), Ron Randel (AgriLife Research-Overton), Penny Riggs (COALS, AgriLife Research), Loren Skow (CVM), Jane Welsh (CVM), Keith Young (TAMHSC-Temple), and Beiyan Zhou (CVM).

“The faculty in our college are well-positioned to facilitate progress at Texas A&M in this area.  They have the training, skills, and abilities to integrate the environment, animal, and human aspects of a problem to solve the complex but very important grand challenges facing our society, such as improving our health,” said Dr. Bill Dugas, Acting Vice Chancellor for Agriculture and Life Sciences and Acting Dean, College of Agriculture and Life Sciences.

The focus of this initiative is to further develop the understanding of genetic and environmental factors, including stress, that can disrupt metabolic functions in humans and animals, which may lead to a variety of chronic conditions such as cardiovascular disease, obesity, and diabetes, and a reduction in productivity.

“There are numerous undesirable conditions that can arise when an animal or person cannot maintain a healthy balance,” said Welsh. “Our approach includes four separate projects, each of which will investigate environmental and genetic factors influencing the regulation of metabolic health. By learning how to manage these factors, we will be able to reduce susceptibility to chronic disease in humans and animals, and also reduce stress on animals that affects their productivity.”

Two pilot projects will focus on behavior and stress related to metabolism. These will include the investigation of prenatal stress on calves and, separately, will examine epigenetic changes in human patients diagnosed with Post Traumatic Stress Disorder. Two additional projects include work to determine environmental factors that influence metabolism, as well as the role that microbes in the body (the microbiome) play in metabolic regulation.

“The proposal submitted by Dr. Welsh and this team of investigators holds great promise in creating new understanding of the relationship between the environment, genetics, stress, and the cascade of chronic diseases that result from stress on the metabolic system,” said Dr. Michael Chaddock, assistant dean for One Health and Strategic Initiatives at the CVM. “Interdisciplinary approaches such as this that advance knowledge that will improve global health is at the very core of the definition of One Health.”

The One Health Initiative was started at Texas A&M in 2011 to be a collaborative effort of multiple disciplines working locally, nationally, and globally to attain sustainable optimal health for the ecosystem. It’s driven by agents of change which include, but are not limited to, population growth; nutritional, agricultural and trade practices; globalization; shift in land use; accelerated urbanization; deforestation; encroachment on wildlife; and climate change.

“This research program represents well what the One Health Grand Challenge at Texas A&M University is all about,” said Dr. Eleanor M. Green, the Carl B. King Dean of Veterinary Medicine at the CVM. “Facilitated by Dr. Michael Chaddock, investigators came together from across campus to form the research team dedicated to finding extraordinary solutions for these diseases of importance to Texas and beyond. Equally impressive is the funding of this project, which was also a team approach. Dr. Glen Laine, vice president for research at Texas A&M, matched voluntary contributions from the involved colleges to fully fund this challenge proposal.”

New research reveals how wild rabbits were genetically transformed into tame rabbits

COLLEGE STATION, Texas – The genetic changes that transformed wild animals into domesticated forms have long been a mystery. However, an international team of scientists has made a breakthrough by showing that many genes controlling the development of the brain and the nervous system were particularly important for rabbit domestication, according to a study published today in the journal Science.

Wild European Rabbits
Two baby wild European rabbits sit outside their burrow at a rabbit warren in the UK

The domestication of animals and plants, a prerequisite for the development of agriculture, is one of the most important technological revolutions during human history. Domestication of animals started as early as 9,000 to 15,000 years ago and initially involved dogs, cattle, sheep, goats, and pigs. The rabbit was domesticated much later, about 1,400 years ago, at monasteries in southern France. When domestication occurred, the wild ancestor, the European rabbit (Oryctolagus cuniculus), was confined to the Iberian Peninsula and southern France.

“There are several reasons why the rabbit is an outstanding model for genetic studies of domestication,” said Miguel Carneiro, from CIBIO/Inbio-University of Porto, one of the leading authors on the paper. “Its domestication was relatively recent, we know where it happened, and this region is still densely populated with wild rabbits.”

The scientists first sequenced the entire genome of one domestic rabbit to develop a reference genome assembly. Then they re-sequenced entire genomes of domestic rabbits representing six different breeds and wild rabbits sampled at 14 different places across the Iberian Peninsula and southern France.

“No previous study on animal domestication has involved such a careful examination of genetic variation in the wild ancestral species,” said Leif Andersson of Uppsala University, Swedish University of Agricultural Sciences, and Texas A&M University. “This allowed us to pinpoint the genetic changes that have occurred during rabbit domestication.”

This domestication has primarily occurred by altering the frequencies of gene variants that were already present in the wild ancestor. “Our data shows that domestication primarily involved small changes in many genes, and not drastic changes in a few genes,” continued Andersson.

The team observed very few examples where a gene variant common in domestic rabbits had completely replaced the gene variant present in wild rabbits; it was rather shifts in frequencies of those variants that were favored in domestic rabbits.

“The results we have are very clear,” Carneiro said. “The difference between a wild and a tame rabbit is not which genes they carry but how their genes are regulated-when and how much of each gene is used in different cells.”

The study also revealed which genes have been altered during domestication, most noticeably strong enrichment in domestic rabbits of genes involved in the development of the brain and the nervous system.

The study shows that the wild rabbit is a highly polymorphic species that carries gene variants that were favorable during domestication, and that the accumulation of many small changes led to the inhibition of the strong flight response-one of the most prominent phenotypic changes in the evolution of the domestic rabbit.

“We predict that a similar process has occurred in other domestic animals and that we will not find a few specific ‘domestication genes’ that were critical for domestication,” Andersson said. “It is very likely that a similar diversity of gene variants affecting the brain and the nervous system occurs in the human population and that contributes to differences in personality and behavior.”

Solving the Mystery of Horse Reproduction

Dr. Leticia Vivani
Dr. Leticia Vivani

Although human in vitro fertilization (IVF) has been successful since the 1970s, similar reproductive technology in horses has lagged behind. Success rates stubbornly hover between zero and 30 percent, and only two live foals have been born using IVF.

Dr. Leticia Vivani

The main problem seems to be with the ability of sperm to penetrate the egg. Ongoing research, much of it at Texas A&M University, has led to the ability to successfully mature horse oocytes in vitro. However, achieving in vitro sperm capacitation – which involves a series of changes that sperm must undergo in order to be able to fertilize an egg-has proven to be more complicated. A solution may soon be at hand, though; Dr. Leticia Vivani, a Ph.D. student working jointly in Dr. Katrin Hinrichs’ and Dr. Dickson Varner’s labs at the Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM), is working on the reasons behind this problem.

“We are trying to understand the factors that regulate the process of sperm capacitation,” Vivani said. “Of course, this happens perfectly well when we breed a mare, but not when we try to mimic this in vitro. We do not know the reason, but I am almost sure there is something ‘special’ within the mare reproductive tract, something that might not be needed in other species, but that makes stallion sperm undergo all these changes.”

Hinrichs’ lab has determined that for some reason, equine sperm are different from those of  other species. For example, incubation conditions that successfully induce hyperactivation (the whip-like tail motion needed to penetrate the egg) and subsequent fertilization in other species fail to do so with equine sperm. “There can be so many things that can be affecting capacitation, and there is very little research done on equine sperm physiology,” Vivani said. “This is good, in a way, because anything you do is new, is innovative, but at the same time, the research can be very challenging and frustrating.”

Some progress is being made in understanding equine sperm capacitation. In 2009, by inducing hyperactivated motility with a substance called procaine, researchers at Cornell University achieved the highest fertilization rate to date (61%). Unfortunately, this is not a practicable solution for embryo production because procaine is toxic to the embryos. “This was nevertheless an important finding,” Vivani said, “because it showed us that the failure of IVF was likely due to a sperm-related problem. We now know that there is something difficult about inducing appropriate equine sperm motility in vitro, and that may be why IVF rates have been so low.”

Vivani, who earned her Doctor of Veterinary Medicine (DVM) degree in her native Argentina in 2001 and her Master of Science degree at the University of Massachusetts in 2010, has long wanted to study at Texas A&M with this team of researchers.

“I have been fascinated with equine reproduction, and the reasons behind the failure of IVF in the horse in particular, since my DVM graduation,” Vivani said. “Therefore, I’ve been dreaming of working with Dr. Hinrichs and with Dr. Varner since I was in Argentina. I had been writing to them and calling them for years before I was eventually able to make it work to come to Texas A&M, first as a visiting researcher and then as a Ph.D. student.” She began her program in May 2012 and plans to graduate in 2016.

One Health

“Horses are an excellent model for human comparative studies. Mice, for example, do not age as women do, but the changes that mares undergo are very similar to women’s changes with aging,” Vivani said. “When mares reach a certain age, their reproductive efficiency decreases as a result; changes in hormone levels, follicular development, and oocyte quality are very similar in older mares and older women. So it’s a great model for human medicine.”

Just as in human medicine, owners of horses for whom natural reproduction has failed turn to assisted reproduction technologies. In horses, this often means using intracytoplasmic sperm injection (ICSI), a technique of “bypassing” standard IVF by injecting a sperm directly into the egg (see sidebar). The ICSI technique is also sometimes used in humans, especially when more traditional IVF has not worked. At the moment, the only way to successfully produce a horse embryo in vitro is through the use of ICSI, which many breeders are increasingly using. “However, is not the most physiological way,” Vivani said, “and is not always practical, as it requires time, sophisticated equipment, and trained personnel. That is why I focus on how to make IVF work.”

Ironically, the One Health approach, which usually means translating findings from animals into human medicine, works backward in this case. IVF works well in humans, and has for more than 30 years. However, it is not yet successful in horses, and perhaps going back to the basics of reproduction can help explain why that is the case.

“In the beginning basic research was hard for me,” Vivani said, “because I was trained as a veterinarian and I just wanted to see results. My advisor for my master’s degree, who is a basic researcher, made me stop and ask why things work or not, and I’m very grateful that he did.” In fact, the IVF technique was pioneered through basic research that led to the discovery of capacitation.

“Dr. Hinrichs and other researchers like her have focused on really understanding physiological processes related to reproduction,” Vivani said. “For many years we, working in equine reproduction, tried one thing and if it didn’t work, we tried a completely different thing without trying to figure out why it didn’t work, and this process explains why there is so little information in this area.”

Despite all of the challenges, Vivani says that she finds her work extremely satisfying, partly due to her excellent mentors. “Dr. Hinrichs and Dr. Varner are so encouraging with their students and really value their work,” Vivani said. “They always encourage me to learn as much as I can. Studying with them has been a wonderful experience-truly a dream come true.

Texas A&M University Institute for Advanced Study Brings World-Class Researchers To Aggieland

Dr. Leif Andersson
Dr. Leif Andersson

The Texas A&M University Institute for Advanced Study (TIAS), established by the Texas A&M University System Board of Regents in December 2010, provides a catalyst to enrich the intellectual climate and educational experiences at Texas A&M. It is a mechanism for attracting world-class talent to the University. The Texas A&M College of Veterinary Medicine & Biomedical Sciences (CVM) has benefited from the program with the addition of Dr. Leif Andersson, a 2013-16 TIAS Faculty Fellow from Uppsala University, Sweden, to the Department of Veterinary Integrative Biosciences (VIBS).

Andersson was chosen as a recipient of the 2014 Wolf Prize in Agriculture, often referred to as equivalent to the Nobel Prize.

“Dr. Andersson is highly deserving of the Wolf Prize in Agriculture,” said Dr. David Threadgill, professor and director of the Whole Systems Genomic Initiative (WSGI) at Texas A&M. “He is the leading geneticist using the latest genomic tools to reveal the genetic control of many important production traits in agricultural animals. There is no other scientist who has been as successful over the last 10 years as Dr. Andersson has been in studying many different species and traits.”

As a TIAS fellow, Dr. Andersson has been collaborating with faculty in the CVM since November 2013 (see sidebar). His research involves comparing the genomes of many species of domestic animals to discover the molecular mechanisms and underlying traits that are important to human and veterinary medicine. Texas A&M University System Chancellor, John Sharp, who initiated the investment in TIAS, said, “We are all very proud of TIAS and specifically, Dr. Andersson. His work will influence the future of sustainable food production for the entire world.”

Dr. Andersson analyzes interbreeding among species of domestic animals to identify the genes and mutations that affect specific traits. This research has led to the development of genomic and marker-assisted selection as a means to identify breeding stock with specific useful and economically important characteristics. These advances in livestock selection have replaced the more classic selection methods based on visible traits, and are an essential contribution to sustainable feeding of a growing world population.

“I congratulate Dr. Andersson on being awarded the prestigious Wolf Prize. His breakthrough work in genomic technologies is an example of the positive impact that he and our Texas A&M University faculty are having on Texas, the nation, and the world,” said Dr. Mark Hussey, interim president of Texas A&M University.

One area of Dr. Andersson’s research with potential crossover to humans is his work on the genetic basis of muscle physiology and motor coordination in horses. This has led to insights into how their genes affect their gait. These discoveries may also have important implications for human diseases such as cerebral palsy.

“We are excited about Dr. Andersson’s recognition as a recipient of the Wolf Prize in Agriculture,” said Dr. Eleanor M. Green, the Carl B. King Dean of Veterinary Medicine. “His international reputation and expertise in functional genomics, combined with the world-class genomics faculty already in place at the CVM, will be integral in fostering innovative One Health collaborations and leading-edge discovery. Special thanks to TIAS and to our university leadership, who provided the opportunity to bring these world-renowned scholars to our campus.  This effort, led by Texas A&M University Chancellor John Sharp and directed by Dr. Junkins, has provided a wealth of opportunity to Texas A&M and to the communities we serve.”

The new Wolf Prize laureates will receive their awards in May from the president of Israel and Israel’s minister of education during a ceremony at the Knesset Building (the seat of Israel’s Parliament) in Jerusalem. “I am extremely proud to be recognized with an international prize of this dignity,” Dr. Andersson said. Five or six Wolf Prizes have been awarded annually since 1978 to outstanding individuals in the fields of agriculture, chemistry, mathematics, medicine, physics, and the arts. According to the Wolf Foundation’s website, a total of 253 scientists and artists from 23 countries have been honored to date. This year, five prizes were awarded to eight individuals in four countries. Dr. Andersson is the fourth agriculture winner of the Wolf Prize associated with Texas A&M: Dr. Perry Adkisson won in 1995, Dr. James Womack in 2001, and Dr. Fuller Bazer in 2002.

“This recognition of the excellence of his work is also reflective of the overall quality of the stellar talent TIAS is attracting as Faculty Fellows,” said Dr. John Junkins, distinguished professor of aerospace engineering, and founding director of TIAS. “Each year, TIAS is bringing the finest academics in the world to Texas A&M for collaboration with our faculty and students.  Of the first 15 scholars that TIAS has brought to Texas A&M, two have won the Nobel Prize, one has been awarded the National Medal of Science, and now one has been awarded the Wolf Prize. Indeed, we are delighted by the ongoing contributions to our programs by all 15 of the highly distinguished scholars attracted to date as TIAS Faculty Fellows.”

Andersson has also contributed to two major ongoing Texas A&M research projects: development of new mouse models for comparative genomics and animal genome re-sequencing. He has been instrumental in the latter by opening possibilities for collaboration with groups conducting next-next generation single cell sequencing (such as Evan Eichler at the University of Washington, Seattle; PacBio sequencing group at BioMedical Center Uppsala, Sweden).

“We are extremely fortunate to be hosting Dr. Andersson as a TIAS fellow in our department, where he is a delightful and inspiring colleague,” said Dr. Evelyn Tiffany-Castiglioni, associate dean for undergraduate education, professor, and head of VIBS. “Dr. Andersson works across a broad range of species; this and his extraordinary powers of observation have been of tremendous value to faculty and students in the college.”

Andersson directed the Animal Genetics component of the Nordic Centre of Excellence in Disease Genetics (NCoEDG) that was in operation until 2011 and his research group has done pioneering work in this field. NCoEDG involved investigators from Denmark, Finland, and Sweden working in five Nordic Universities pooling their expertise, methodological power, and resources to study the genetic background of metabolic syndrome, autoimmune and inflammatory diseases, and colon cancer. Dr. Andersson’s expertise in animal model development and experience with multi-institutional collaborative research in NCoEDG can provide exceptional insights as the CVM positions itself to become a major contributor to the WSGI and the One Health program.

A world-renowned scientist who has published more than 330 scientific articles and has received six patents and filed applications for two more, Dr. Andersson has mentored 25 students to doctorate or professional degrees. He has also been uniquely elected to four major scientific royal societies in Sweden (Royal Swedish Society for Agriculture and Forestry, the Royal Swedish Academy of Sciences, Royal Society of Sciences in Uppsala and the Royal Physiographic Society in Lund) and was recently elected as a Foreign Member of the U.S. National Academy of Sciences. Dr. Andersson has received numerous other prizes: the Thureus Prize in Natural History and Medicine from the Royal Society of Sciences, the Linneus Prize in Zoology from the Royal Physiographic Society in Lund, the Hilda and Alfred Eriksson’s Prize in Medicine from the Royal Swedish Academy of Sciences, and the Olof Rudbeck Prize from Uppsala Medical Society.

Dr. Andersson’s CVM Collaborations

Dr. Bhanu Chowdhary, Dr. Terje Raudsepp, and her graduate student, Sharmila Ghosh:

  • Re-sequencing of the horse pseudoautosomal region
  • Characterization of a deletion in the horse associated with a developmental disorder
  • Characterization of a deletion associated with equine cryptorchidism
  • Discovery of causative genes/mutations for the Dun coat color in horses

Dr. Jim Womack, his postdoctoral fellow, Dr. Mi Ok Lee, and his graduate student, Jungfeng Chen:

  • Re-sequencing a NKlysin immunity related region in cattle genome

Dr. Gus Cothran:

  • Equine gaits (Manuscript in press in Animal Genetics, follow up from a previous Nature paper, leading to a Texas A&M Genomics Seed grant)

Dr. Loren Skow and graduate student, Erica Downey:

  • Bovine MHC (leading to a Texas A&M Genomics Seed grant)

Dr. David Threadgill:

  • Mouse knockout models

Research Offers Hope for Spinal Cord Injuries: How a Clinical Trial in Dogs May Help Human Patients

Dr. Jonathan Levine
Dr. Jonathan Levine

Dr. Jonathan Levine’s research on spinal cord injuries in dogs may one day help humans with similar injuries. The United States Department of Defense seems to think so, as they have funded a large-scale, three-year clinical trial of dogs with injuries resulting from intervertebral disc herniation. While humans with spinal cord injuries (SCIs) usually sustain these due to trauma, canine disc herniation does mimic certain facets of human injury.

Importantly, canine disc herniation results in spinal cord bruising and compression, as is the case with trauma in humans. Additionally, the treatment for canine disc herniation is amazingly similar to that which is administered to humans with spinal cord trauma.

“The animals get an MRI, they get surgery, and they get rehabilitation,” said Levine, who is an associate professor in the Department of Small Animal Clinical Sciences at the Texas A&M College of Veterinary Medicine & Biomedical Sciences.

Tracking limb movement
Using infrared cameras that track limb movements, the team measure how normal versus injured dogs walk.

Using dogs with naturally occurring neurological conditions, as opposed to rodents with induced injuries, gives a much more realistic view of how a drug might perform in humans. However, the study is also much more complicated because the researchers don’t have control over a number of factors. Unlike rodents, dogs vary widely in their genetics, the location and severity of the injury, and time before treatment begins. Human SCIs, of course, have similar variability.

“If a drug doesn’t work on dogs, that is a good indication that it might not work in humans either,” Levine said. On the other hand, of course, something that does work well in dogs is very promising for human injuries.

One of the ways to determine if a treatment works is to measure recovery of various functions, especially movement. Using infrared cameras that can track limb movements, Levine and his team measure how normal versus injured dogs walk. Then, in separate collaborative projects with bioengineers at the University of Louisville, the team can determine which muscles are activated.

“It is a very collaborative process,” Levine said. “There are about 20 people, at a number of different institutions, who are vital to our entire program.”  The study with the U.S. Department of Defense is a joint effort with investigators at UC San Francisco Medical School. Scientists at University of Louisville, Methodist Hospital, and UT Houston Medical School are participating in an array of other projects.

“Dr. Levine’s approach is a perfect example of One Health research,” said Dr. Eleanor M. Green, the Carl B. King Dean of Veterinary Medicine. “The goal of his trial is to determine how best to treat dogs with this common injury, but in so doing he is gathering valuable data that can be used to benefit future human clinical trials.”

 

 

Technicians fit sensors that will measure the dog's limb movement.
Technicians fit sensors that will measure the dog’s limb movement.

The drug Levine and his colleagues are evaluating in the U.S. Department of Defense canine clinical trial is a type of neuro-protective therapy, meaning it is thought to protect the cord by stopping events that happen soon after injury that actually make injury worse. Specifically, the drug blocks enzymes called metalloproteinases that are released after injury. These enzymes break down the extracellular matrix and allow white blood cells into the spinal cord, which only does more damage. However, these same enzymes can be useful at later stages of injury, after the body has started the healing process and has begun to form scar tissue. When the enzymes are inhibited at later stages, the patients tend to do poorly, which is why the drug therapy has to be timed perfectly.

“If we can get to these dogs in the first 48 hours after their injury,” Levine said, “we can give this drug-and the dogs-their optimal chance.”

If you have a dog or a patient you think might be a candidate for Levine’s clinical trial, please contact Alisha Selix (aselix@cvm.tamu.edu) or Elizabeth Scanlin (escanlin@cvm.tamu.edu) at 979-845-2351.

Researcher Uncovers Multiple Influences in the Antibiotic Resistance Debate

COLLEGE STATION, Texas – The issue of antibiotic resistance may have only recently become front-page news, but it has always been a concern of those focused on improving public health. Alexander Fleming, a recipient of the 1945 Nobel Prize in Medicine for his discovery of penicillin, warned during his acceptance speech for the award of the possibility of resistance developing if antibiotics were used inappropriately. Nearly seventy years later, his cautionary words and those of other public health experts have become a troublesome reality.

Dr. Morgan Scott
Dr. Morgan Scott

ABR has developed over time similar to “a 40- or 50-year smoldering fire,” said Morgan Scott, a professor in the Department of Veterinary Pathobiology at the Texas A&M College of Veterinary Medicine & Biomedical Sciences. Although antibiotic misuse and overuse in humans and animals has stoked that fire and shortened the time between introduction of a given antibiotic and formation of resistance, bacteria would have eventually developed a tolerance for the drugs even with thoughtful antibiotic use. “When it comes to antibiotic use and bacterial resistance, the only thing we really know for certain is that less use is better; however, zero use is clearly not an option,” Scott said.Antibiotic resistance (ABR) develops when an antibiotic drug loses its effectiveness against bacteria. Through genetic mutation and selection, bacteria can evolve defenses against a given antibiotic. Some “superbugs,” such as methicillin-resistant Staphylococcus aureus (MRSA), require difficult, costly treatment; in some cases, treatment may not even be possible or feasible.

Scott’s research in antibiotic use and resistance began in biomedical science and epidemiology, but soon included work in other fields as his interest in the subject expanded.

“Most of my research has been on studying the use of antibiotics and the resistance and potential risk to public health that result,” he said. “I’ve used a multitude of scientific approaches from molecular biology to ecology and everything in between, and I’ve looked at the changing risk that is associated with different uses of different antibiotics and different regimens. But behind all of that was this nagging suspicion in the back of my mind that no matter what we find, none of it will matter unless we actually understand what motivates people to use antibiotics in the first place, what the barriers are to any potential behavioral change.”

One aspect of Scott’s research, in collaboration with Dr. Alex McIntosh, professor in the Department of Sociology at Texas A&M University, examined the social psychology of antibiotic use among veterinarians. They found that several factors influenced why and how antibiotics are used, including policy, economics, social norms regarding treatment, and a belief that antibiotics are “a good thing to do.”

“When you start understanding the behavior, you start to realize that the aggregate that defines the perceived behavioral constraint is the policy and the regulations that oversee the use of antibiotics as well as the unwritten policy of why people do what they do,” said Scott.

Scott, along with collaborators at Texas Tech and Hull University in the United Kingdom, is now looking at systems approaches as ways to understand policy and how it can be structured to include as many viewpoints as possible. They have identified that numerous “stakeholders”-including physicians, patients, veterinarians, livestock producers, pharmaceutical companies, public health agencies, and healthcare and consumer advocacy groups-have both an interest and role in countering ABR. This dynamic has the potential to facilitate an unofficial town-meeting style of democracy among the stakeholders that would allow each group to have a direct impact on the creation and implementation of ABR policy.

However, despite their mutual interest in combating resistance, members of these stakeholder groups are not always in agreement: one group suggesting that antibiotics are overused, and the other group countering by saying that the current use of antibiotics is essential to preserve health. According to Scott, this division appears to be growing.

“I see the separation of thoughts, ideas and opinions,” Scott said. “It is a given that we must work together toward a well thought out, coordinated response to ABR.” He likened the use to “drawing down a finite resource that has to be carefully managed for maximum benefit to both the individual and community.”

“As you use more and more antibiotics, you will have fewer and fewer bacteria that are susceptible,” he said. “My use today will diminish in some way your use in the future; these are the economics of a finite resource.”

Scott strongly believes that this divide should be bridged by mutual understanding in the interest of finding workable solutions for dealing with ABR.

“I would like both groups to step back and see aspects of the other side’s argument that might hold some validity and should be considered,” Scott said. “I think there’s far more benefit to having reasonable people communicating to the majority of those who consume and feel comfortable with the products. Transparency is a key to successfully managing ABR.”

The problem presented by ABR arose slowly and through multiple decisions and actions. Creating policy to counter that problem will also require numerous decisions and then implementation in order to be successful.

“We always need to seek alternatives to antibiotics because of the documented potential for any antibiotic to select for resistance to almost any other antibiotic,” said Scott.