Saturday, July 19, 2014

H3N8 structure determined – canine influenza originated in horses

Canine influenza is a highly contagious respiratory infection of dogs caused by a novel influenza virus (H3N8) that was first discovered in 2004. Like influenza in other species, the canine influenza virus causes a cough, sneezing and nasal discharge. A fever may also occur, but it is usually transient and rarely noticed by dog owners. H3N8 cannot be distinguish from other respiratory infections without diagnostic tests.

All dogs exposed to H3N8 become infected; about 80% become ill, the other 20% show no symptoms. Recovery time is about two weeks but some dogs progress to pneumonia, which is usually due to secondary bacterial infections. While the mortality rate for canine influenza is very low, the secondary pneumonia can be life-threatening in some cases. Canine influenza is an emergent disease in dogs.

Collins et al. (2014) recently used x-ray crystallography to determine the structure of the H3 hemagglutinins (HAs) in two different equine viruses and the canine virus. They found all three are very similar in structure with the majority of amino acid sequence differences between the two equine HAs located on the virus membrane. HAs of canine viruses are distinct in containing the amino acid substitution Trp-222→Leu in the receptor binding site that influences specificity for the receptor. In the canine and recent equine virus HAs a unique difference is observed by comparison with all other HAs examined to date. Analyses of site-specific mutant HAs indicate that a single amino acid substitution, Thr-30→Ser, influences interactions between N-terminal and C-terminal regions of the subdomain that are important in the structural changes required for membrane fusion activity. Both structural modifications may have facilitated the transmission of H3N8 influenza from horses to dogs.

The authors summarized the situation as follows. Equine influenza viruses of the H3N8 subtype were first isolated in 1963 from race horses in Miami. Since then they have caused numerous outbreaks of infection in horses around the world with serious disease and economic consequences. In 2004, again in Florida, an H3N8 virus was isolated from an outbreak of canine influenza and similar viruses have since been isolated from dogs in the United States and in Europe. Genetic comparisons indicate that the canine viruses are closely related to equine viruses that were in circulation in horses around 2000. In studies of differences in equine viruses isolated since 1963 and between equine and canine viruses, the sequences of genes for the hemagglutinin membrane glycoprotein (HA) have been compared. Sequence data for equine virus HAs indicate the evolution of four distinct lineages. The first was associated with antigenic drift, between 1963 and 1980, and following this three separate branches formed a “Eurasian” lineage, an “American” lineage, and a divided lineage containing two clades, “Florida” clade 1 and Florida clade 2. The HAs of the canine viruses are most similar to those of Florida clade 1 equines. The majority of amino acid sequence changes revealed from the analyses are in the HA1 component of HA, some in regions known to be antigenically important in H3 HAs, and several near the receptor binding site.

The pdf is available on-line.

Citation
Collins, P. J.,  et al. (2014). Recent evolution of equine influenza and the origin of canine influenza. Proceedings of the National Academy of Sciences, 201406606.

Friday, July 18, 2014

Dogs are scavengers first

Much of what has been written about dogs is undoubtedly nonsense. And, we will leave the critique of popular TV dog shows for the future. While dogs and wolves undoubtedly shared a common ancestor, it seems improbable that dogs were originally modified from wolves by artificial selection by humans. After all, abandoned dogs do not revert to being wolves, they become just feral dogs. Have humans selected dogs for various traits (color, body size, temperament, etc.) in recent times – undoubtedly they have. But, humans probably had little to do with getting a population of wolves to evolve into the dog. The animal that is generally considered the oldest domesticated species.
A free-ranging dog scavenging leatherback sea turtle nests
on Grande Riviere Beach on the north coast of Trinidad. Note
the large number of black vultures also present. JCM

In chapter 10 of the recently published book, Domestic Dog Cognition and Behavior, titled “A Dog’s-Eye View of Canine Cognition” by Udell, Lord, Feuerbacher and Wynne the authors suggest the following.

Most dogs are scavengers and live on the periphery of human society. These dogs are more likely to avoid human contact than seek it. While pet dogs have been a major focus of recent research is unlikely that the human-dog bond is a special adaptation that is the result of co-evolution, but rather the bond is the expression of basic processes such as conditioning, socialization and biological traits that are shared by domestic and wild canids. Individual dogs that have been socialized to humans and become dependent on them have high levels of sensitivity to human actions. Udell and colleagues argue that the fundamental differences between dog and wolf behavior lie at more basic levels: in the processes of socialization, foraging, and reproduction. Small but crucial intertwined changes in the ancestral dog population led dogs to (1) become more promiscuous than any other canid, (2) be able to reproduce more rapidly than wolves, (3) be a much less effective hunter but (4) dogs are more efficient scavenger than other canids. The authors view the indirect consequences of these changes as producing dogs, and suggest that while “…it may be a little less flattering to the human species, we believe this perspective on dogs is at least as fascinating and closer to the historical truth than the story that humans created dogs.”

Citation
Udell, M. A., Lord, K., Feuerbacher, E. N., & Wynne, C. D. (2014). A Dog’s-Eye View of Canine Cognition. In Domestic Dog Cognition and Behavior (pp. 221-240). Springer Berlin Heidelberg. A pdf of this chapter can be found on-line.

Some of my early experiences with dogs

In the early 1980’s during a reptile survey on Trinidad I was watching a lizard, an Amieva or as the Trinidadians call them, a zandolie, forage for insects at the edge of a dump. My binoculars were focused on the lizard’s movements and it was several minutes before I realized Turkey Vultures had gathered on the waste pile. The birds had surrounded a severely emaciated puppy with its ribs clearly visible through its severely ulcerated skin. The dog’s death was imminent.  The birds moved closer and soon my view of the dog disappeared amid a flurry black feathers.
Biology tells us that all organisms produce far more offspring that can be expected to survive. This was one of Charles Darwin’s founding principles for natural selection and an idea he may have gleaned from Thomas Malthus’ Essay on Population. Over production of offspring allows the environment to select the individuals best adapted to local condition to survive and reproduce, while those individuals least fit for the environment are eaten by predators, or they become diseased, and unable to find shelter – they become victims of the climate and food for scavengers and decomposers. Despite my understanding of this basic principle my gut told me I should save the dog while my brain told me the vultures need food, the dog was too far gone to be rescued, and this is the way ecosystems process matter and energy.  I had observed predation and scavenging numerous times involving many species but never remember feeling the way I did at that dump. Before that point in time I had never owned a dog and the observation increased my curiosity about dogs, humans and myself.
Dogs generate a strong emotional and empathetic response in most of us, perhaps because we identify with them, or perhaps because we know that as humans we are responsible for their plight. Dogs, after all, are human commensals. Rats, cats, cockroaches and, of course dogs, owe their biological success to humans. Humans have created environments where these species thrive by increasing their food supply, habitat, and social environment. But, aside from cats, dogs are the only commensal we have an emotional bond with. The emotion I felt at the Trinidadian dump and the bonds I have formed over the years with several different family dogs are responsible for the title of this blog. There is something quite unique at the core of dog-human relationships and it is the central focus of this blog. Why should a human feel an emotional bond with a dog?  Particularly, if that human had never had extended contact with a dog.
Twenty-five years after the observation in Trinidad I was studying aquatic snakes in Thailand and dogs were often present. Well cared for dogs were the exception, in villages and on the edges of large cities feral dogs are a serious problem. One hotel I stayed at just north of Bangkok was next to a canal with roads paralleling the water on each side. One side of the canal was lined with homes and stores; the other side was abandoned rice paddies. It made an excellent jogging trail for early morning exercise. At this time of day local fishers were throwing cast nets into the canal, and factory workers were on their way to work on an armada of motor bikes. Dogs, lots of dogs, were sleeping on the street and along the dirt road. Most were small, 15 to 25 pounds and often uniform tan in color or with blotches of white or black. Most had skin infections, were severely malnourished, and sometimes followed me for short distances as I walked and jogged along the path. These feral animals resembled my family dogs only in form and they made me nervous – rabies was a potential result of being bitten by one of these animals.
My family’s first dog was purchased in a pet shop. Sara’s fifth birthday was approaching and the only thing she had ever asked for was a dog. Kathie and I had resisted. While I was busy looking at an anaconda for sale in the pet shop, Kathie and Sara were visiting the dogs. One of the employees removed a keeshond puppy from a cage, and it immediately took to following Sara. One pet shop customer, impressed with the dog’s interest in Sara, approached Kathie and said something like, “This is a Kodak moment. You are going to buy her that dog, aren’t you?” We left the pet shop without the dog, had dinner, and returned to buy or rescue the puppy. Sara loved Star Wars, and the dog’s appearance was reminiscent of the Ewok creatures in fur density and coloration, we named him Wicket.
Yes, I know I was not supposed to buy a pet shop dog, it was probably produced in a puppy mill, but I also knew that the dog would have a much better life with us than someone else. Parents of many species go to extremes for their offspring. Biologists call this kin selection and it’s an idea that plays a major role in understanding relationships between dogs and people as well as between members within each species.
Wicket was soon a member of the family. Our fenced-in-yard on a busy street assured him a secure place to play, but there were stairs involved in getting into the yard and the dog was too small to navigate the steps. I spent a considerable amount of time transporting Wicket to the yard during that winter in an attempt to housebreak him.
It was sometime in late winter when I arrived home from school; Kathie and Sara were already there. As I walked in the door Wicket raced back and forth between me and the back door. I followed him to the steps that lead into the yard. What followed is something that animal behavior courses do not prepare you for. The dog was accustomed to me carrying him into the yard. As I opened the door, Wicket raced down the stairs by himself and returned to the top of the stairs, and again raced to the bottom of the stairs and back up. The damn dog was showing me that he could now navigate the stairs by himself and no longer needed my help. Wicket taught me much about behavior and dogs. Another moment of learning came when I walked Sara and the dog to a nearby park. Sara played on the swings and was having a good time and she did not want to leave. While she rarely argued with me, this day she did. I said, “Ok, Wicket and I are going home.” As I walked away from Sara, the dog sat down and I had to pull him down the street in the sitting position. He was not going to leave Sara willingly. This kind of loyalty was not present in the village dogs that followed me along that dirt road in Bangkok. The village dogs had not been socialized.
Wicket lived a good life, despite the fact that he developed epilepsy and need to be treated with drugs for much of his life. After a grand mall seizure he would frequently be confused for hours. After a particularly severe seizure I remember him standing with his head in the corner of a room not knowing how to get out.  After eight or nine years he reached a point beyond which we could care for him, and like many family dogs he had to be euthanized.
I had been thinking about dogs more frequently and it occurred to me that having two may be better for them and increase what I could learn about them. Sara was now in high school and I had found a kennel that bred Samoyeds. During a visit to the kennel the breeder had an 18 month old female that she was interested in selling on a breeding contract. After considerable thought, we agreed. We would buy Taiga and breed her once. Our intention was to keep one of the puppies. Again, I would not recommend this kind of arrangement to people just wanting a dog or two, but I was curious and interested in learning what I could from the experience.
Taiga was large, she weighed about 80 pounds and her wolf-like appearance on the street made many people nervous. While she was exceptionally friendly, she was not at all loyal. She would go off with just about anyone. Shortly after she started living with us there was a snow storm, I had closed the side door to the garage and opened the main door to shovel the driveway. The blowing snow reduced visibility and the wind had popped the side door open. I soon gave up on shoveling and returned to the house only to find the dog gone. Looking for a white dog in a snow storm is like, well you know, like trying to find the proverbial needle. I drove around the neighborhood looking for her without success. We had to be at school and Kathie and I asked everyone if they had seen the dog, one student said he had seen a large white dog getting into a police car not too far from our house. A call to the station confirmed the village police had picked her up after she walked into a neighbor’s house and joined the family for breakfast. The homeowner was retrieving his newspaper and as he entered the house Taiga followed.
Taiga went into estrus and was mated to a male from her home kennel, 60 days later she went into labor. It was early in the morning when the first pup was born and I had already gone to school. Kathie called and insisted I return because she did not want to play midwife. Taiga was having strong contractions but more puppies were not coming through the birth canal. Kathie and Sara went school, leaving me with the dog. Steve was a good friend and a vet and I soon had him on the phone. His first advice was, wait another 10 minutes for the next puppy. I waited 15 minutes and there was no puppy. Another phone call to Steve, and he asked how many puppies were expected? The x-rays had shown nine. Steve’s advice was to wait another 10 minutes. While waiting I called my office and got someone to cover my first class. Ten minutes passed and still no puppy. The third call to Steve, and the advice was the same wait 10 more minutes. I had predicted the response on the fourth call to Steve― get the dog to the local vet. At the vet’s office an injection of oxytocin, a pituitary hormone, stimulated the muscles in the uterus and birth canal to contract and push the puppies out of Taiga. By early evening I picked up the dogs and brought them home.
Taiga delivered nine pups; two had not survived the trip through the birth canal. The surviving pups were housed in a whelping box, and Taiga proved an attentive mother, frequently cleaning and feeding her offspring and, as they became more mobile she kept them from wandering out of box. Despite the fact she had a warm room in the house to maintain her puppies she would often return to the den hole she had started to dig under the house in the backyard.  We had provided a dog door in the wall of the hallway so she could exit the house onto the deck and have access to the backyard. Soon the puppies were following her outside. Once they had reached eight weeks of age the breeder took six of them, we kept two and gave one to some close friends. We kept Rossi, the first puppy born at the house, and the largest male in the litter. Taiga trained Rossi to use the backyard, he required no housebreaking from us and he grew quickly, eventually weighing 100 pounds.
Rossi was highly intelligent and much more loyal than his mother. He would often report his mother’s mischievous deeds to us. Taiga was a consummate counter-surfer; anything edible left on a counter would be found and consumed. One day she found a five-pound bag of M&M candy on the counter, took it to the backyard, and consumed much of it. Contrary to popular belief, chocolate is not always toxic to dogs. Rossi found the wrapper and brought it to Kathie. Taiga also gained a reputation with the cable company for chewing up remotes. You know you have a problem when you see power buttons sticking out of dog poop in the backyard.
Rossi

The ability to mimic behavior is often consider a sign of intelligence and Rossi would mimic emergency vehicle sirens and would even include the sound changes that resulted from the Doppler effect as the emergency vehicles approached and then pass the house. But one day he mimicked me in a quite unexpected way. Rossi was completely house broken; he never had an accident in the house. One day I was mopping the hardwood floors with a sponge mop and a bottle of cleaner. I would squirt some the cleaner onto the floor and then mop the area. Rossi watched me intently. A stream of cleaner would come out of the bottle and I would push it around with the mop. Standing in front of the mop, Rossi released a stream of urine on the floor, directly in front of the mop. I am sure he thought he was helping by mimicking my behavior with the bottle of cleaner. 

Why dogs look like they do - domestication syndrome

A free-ranging dog living at a Trinidad dump. JCM
More than 140 years ago, Charles Darwin noticed something peculiar about domesticated mammals. Compared to their wild ancestors, domestic species are more tame, and they also tend to display a suite of other characteristic features, including floppier ears, patches of white fur, and more juvenile faces with smaller jaws. Since Darwin's observations, the explanation for this pattern has proved elusive, but now, in a Perspectives article published in the journal Genetics, a new hypothesis has been proposed that could explain why breeding for tameness causes changes in such diverse traits.

The underlying link between these features could be the group of embryonic stem cells called the neural crest, suggest the authors. Although this proposal has not yet been tested, it is the first unified hypothesis that connects several components of the "domestication syndrome." It not only applies to mammals like dogs, foxes, pigs, horses, sheep and rabbits, but it may even explain similar changes in domesticated birds and fish.

"Because Darwin made his observations just as the science of genetics was beginning, the domestication syndrome is one of the oldest problems in the field. So it was tremendously exciting when we realized that the neural crest hypothesis neatly ties together this hodge-podge of traits," says Adam Wilkins, from the Humboldt University of Berlin. Wilkins is an editor at Genetics and one of the paper's authors.

Neural crest cells are formed near the developing spinal cord of early vertebrate embryos. As the embryo matures, the cells migrate to different parts of the body and give rise to many tissue types. These tissues include pigment cells and parts of the skull, jaws, teeth, and ears -- as well as the adrenal glands, which are the center of the "fight-or-flight" response. Neural crest cells also indirectly affect brain development.

In the hypothesis proposed by Wilkins and co-authors Richard Wrangham of Harvard University and Tecumseh Fitch of the University of Vienna, domesticated mammals may show impaired development or migration of neural crest cells compared to their wild ancestors.

"When humans bred these animals for tameness, they may have inadvertently selected those with mild neural crest deficits, resulting in smaller or slow-maturing adrenal glands," Wilkins says. "So, these animals were less fearful."

But the neural crest influences more than adrenal glands. Among other effects, neural crest deficits can cause de-pigmentation in some areas of skin (e.g. white patches), malformed ear cartilage, tooth anomalies, and jaw development changes, all of which are seen in the domestication syndrome. The authors also suggest that the reduced forebrain size of most domestic mammals could be an indirect effect of neural crest changes, because a chemical signal sent by these cells is critical for proper brain development.

"This interesting idea based in developmental biology brings us closer to solving a riddle that's been with us a long time. It provides a unifying hypothesis to test and brings valuable insight into the biology of domestication," says Mark Johnston, Editor-in-Chief of Genetics.

Tests of the neural crest hypothesis may not be far off, as other scientists are rapidly mapping the genes that have been altered by domestication in the rat, fox, and dog. The hypothesis predicts that some of these genes will influence neural crest cell biology.

If so, we will have a much deeper understanding of the biology underlying a significant evolutionary event, Wilkins says. "Animal domestication was a crucial step in the development of human civilizations. Without these animals, it's hard to imagine that human societies would have thrived in the way they have."

The full article is available on-line.

Citation
A. S. Wilkins, R. W. Wrangham, W. T. Fitch. The "Domestication Syndrome" in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics. Genetics, 2014; 197 (3): 795 DOI: 10.1534/genetics.114.165423