Man’s best friend just got a little closer to his master. In December 2005, a team of scientists announced in the journal Nature that they had sequenced the entire genome of the domesticated dog. Their report has important implications for the understanding of human genetic diseases, as well as gene-related personality and behavioral traits in humans.
“Humans and dogs have the same gene set,” says Kerstin Lindblad-Toh of Harvard’s Broad Institute and the Massachusetts Institute of Technology, who led the dog genome project. “In fact, every gene in the dog genome is the same as it is in the human genome, with similar function.”
Scientists mapped the complete human genome—the entire set of 23 pairs of chromosomes and the nearly 25,000 genes they contain—in 2003, providing a greater understanding of genetic diseases and insight into human evolution. Lindblad-Toh’s dog genome project sequenced, or determined the order of, the more than 2 billion chemical pairs that make up canine DNA, the molecular basis of heredity. Lindblad-Toh said it took about two years to map the dog genome, which scientists had partially decoded in the past, compared with more than a dozen years to map the human genome.
The Evolution of the Domestic Dog
Canis familiaris, the domestic dog, is a direct descendent of the gray wolf of East Asia and traces its roots back nearly 15,000 years (dogs themselves go back even farther, possibly 100,000 years). DNA studies show that the first domestic dogs in North America traveled with humans when humans migrated from Asia about 12,000 years ago.
In recent centuries, says Lindblad-Toh, humans selectively bred dogs to achieve a variety of physical outcomes including size, shape, and coat color, as well as skills at herding, hunting, and obedience. Because of this selective breeding, there are more than 400 distinct domestic dog breeds throughout the world today.
One offshoot of this breeding, Lindblad-Toh and her colleagues wrote in Nature, is that dogs show a “high prevalence of specific diseases, including cancers, blindness, heart disease, cataracts, epilepsy, hip dysplasia and deafness.” Most of these diseases are also seen in dogs’ human companions, with similar clinical manifestations.
Closer to Us than Chimpanzees
Dogs may be considered “man’s best friend” because they have lived so closely for such a long period of time. This closeness, scientists have found, has altered dogs’ cognitive abilities such that they share many personality and behavioral traits with humans.
Anthropologist Brian Hare of the Max Planck Institute for Evolutionary Anthropology in Germany has reported that domesticated dogs are better at reading human communication signals, such as glances or pointing, than chimpanzees, which have long been thought to be closer to humans than any other primate.
In a presentation to the American Association for the Advancement of Science in 2004, Hare reported findings from his research on a subspecies of wild dogs from New Guinea that were once domesticated but have lived without significant human contact for thousands of years. Hare’s study involved concealing food under one of two cups and having a human gesture toward the cup covering the food.
Few of the wild dogs approached the food cup more than half the time, as statistical analysis would suggest; however, almost all of the domesticated dogs in the study found the food after following the human’s gesture. Hare says that these findings show that constant human contact over the years has led domesticated dogs to acquire the ability to read human communication signals, much the way a young child does.
“This is where co-evolution comes in,” Lindblad-Toh says. “We have the same gene sets, we live together, and we respond to the same types of cues, visual and otherwise. This helps us learn about important gene functions over time.”
Lindblad-Toh says that further evidence of dog-human co-evolution comes from studies of dogs, mice, and humans that show how specific brain genes have evolved more quickly in both dogs and humans, but not in mice. These studies, she says, show a good correlation in the genetic evolution of the two species.
A boxer named Tasha was chosen from more than 60 breeds for the sequencing of the dog genome because boxers have relatively little genetic variation. Because dogs and humans have co-evolved, the dog genome could lead to clues about human diseases. Photo Courtesy of The Broad Institute
Victoria Wobber, a Max Planck researcher who collaborates with Hare on canine genetic research, says one of the most important points in Lindblad-Toh’s paper is the finding that the rate of genetic change in the brain is similar in dogs and humans, suggesting that both species have evolved their functionally innovative behaviors quite quickly.
“This demonstrates that humans are not unique in their rapid rate of genetic change, and that another species evolved at a similarly fast rate and could have experienced just as drastic behavioral changes,” Wobber says.
The Human Brain Connection
The dog genome may tell us as much about humans as it does about dogs. Lindblad-Toh says the potential benefits of this knowledge include insights into disease mechanisms, which may lead to therapies to treat both species. Dogs and humans share similar brain diseases, including epilepsy, narcolepsy, and brain tumors, as well as such behavioral disorders as obsessive-compulsive disorder and hyperaggressiveness.
Lindblad-Toh and her team identified nearly 2.5 million genetic differences among breeds of dogs. These small genetic changes or variations that occur in DNA are called single nucleotide polymorphisms, or SNPs. They do not produce physical changes, but scientists believe they may predispose dogs—or people—to disease and may even influence their response to drugs.
Using these SNPs, the scientists created haplotype blocks—sites of closely located SNPs that are inherited in blocks—which are almost 100 times larger in dog populations than they are in humans.
“The haplotype structure in dogs is more advantageous for finding disease genes [than it is in humans],” Lindblad-Toh says. “Because these building blocks are very big in dogs, it’s easier to find these disease genes in dogs.”
Because the gene set in dogs and humans is so similar, once a disease gene is identified in a dog, the corresponding gene in humans should be easy to identify.
“The genetic contributions to many common diseases appear to be easier to uncover in dogs,” says Lindblad-Toh. “This is a significant step forward in understanding the roots of genetic disease in both dogs and humans.”
Benefits of the Dog Genome
Lindblad-Toh and other scientists consider the mapping of the dog genome to be only the “tip of the iceberg” in terms of understanding the genetic link between dogs and humans.
Armed with this new knowledge, researchers can now find traits and disease genes in dogs and translate them to human genes; better understand the on/off signals in human genes that determine how neuronal connections are made; and learn about the wiring of the two species’ brains to determine if there are similarities.
“The dog genome gives us the basic tools to look in detail at the brain,” says Lindblad-Toh. “This is a parts list that helps us understand how genes, including brain genes, have evolved and function.”