Big Dog, Little Dog

How IGF and humans influenced dog size
Imagine if some adult humans were the size of giants and others were the size of two-year-olds. That's the weird kind of world that dogs live in. People just aren't that different when it comes to size. Most adults are about the same height – 5 to 6 feet. In fact, most species are roughly the same size. Except for dogs. The smallest dog, a Chihuahua, is just about 5 inches tall. The largest dog, a Great Dane, is over 7 feet tall when he stands on his hind legs. That's the same as the shortest humans being 2 feet tall. And the tallest humans being over 31 feet tall. Wow! The modern-day dog that you have around your house is descended from gray wolves. The curious thing is that gray wolves, like almost every other species, are all about the same size too. So what makes dogs so special? A group of scientists in the United States and England asked the same question. They looked to dogs' DNA for the answer.
One gene explains the vast size differences between dog breeds
Scientists had already thought that DNA contained the answer for why dogs are such different sizes. Because each dog breed is always about the same size. For example, Golden Retrievers are usually 20-24 inches tall at the shoulders. With that much consistency in size, DNA must be playing a role. They just didn't know what about the DNA caused the size variation. To figure it out, the scientists used the Portuguese water dog. It comes in both small and large sizes making it an ideal dog to study. If there is a specific gene or bit of DNA responsible for differences between large and small dogs, it should be in the Portuguese water dog. The scientists already knew that DNA in a region of chromosome 15 held the key to dog size. So they sequenced the DNA, or determined what each letter of DNA was, on that region of chromosome 15 in large and small Portuguese water dogs. The sequencing revealed mutations or differences in the DNA between the large and small Portuguese water dogs. Some of the differences were very tiny. In fact, only a single letter of DNA was different in some places between the dogs. These single letter differences are called single-nucleotide polymorphisms (SNPs – pronounced "snips"). One common use for SNPs is determining who a baby's father is. The scientists found 302 SNPs. That's a pretty small number considering they were looking at 15 million letters of DNA. Then they looked at 116 of these SNPs in 463 Portuguese water dogs. The scientists used statistics to figure out how well each SNP correlated to the size of the dog's skeleton. The best correlation was found near the insulin-like growth factor (IGF) gene. This was very encouraging because we already knew that IGF had something to do with body size. IGF interacts with almost every cell in the body. It controls cell growth and the way cells get energy. Best of all, IGF influences the size of humans and mice. So maybe it plays the same role in dogs. To figure this out, the scientists looked at IGF in 926 Portuguese water dogs. 96% of the dogs had one of two IGF types – the "small" allele or the "large" allele. Small dogs usually had the small type. Large dogs usually had the large type. But is IGF important in other dog breeds besides the Portuguese water dog? The scientists looked at IGF type in 23 small and 20 giant dog breeds. Only the small and large IGF alleles were significantly different between small and giant breeds. Thus far, they'd only been dealing with small numbers of dogs. So to confirm that IGF helps determine dog breed size, the scientists looked at IGF type in 3241 dogs from 143 breeds. Presto! A breed's IGF type predicted the average dog size of the breed. Within a breed, the percent of dogs that had the small IGF allele predicted how small that dog breed was. So this one gene, IGF, is a major contributor to dog size. This finding is quite a surprise. Body size is very complicated. Scientists thought that many genes were probably involved. And there are. IGF is a big determinant of overall breed size. Like the difference between a German Shepherd and a toy poodle. But lots of genes are probably involved in making one German Shepherd a bit bigger or smaller than another one. This is how height works in people. People are like one breed of dog - all about the same size. Numerous genes help determine height in people. Presumably like the other genes that contribute to differences in dog sizes within a breed. Each of these genes only contributes a small bit to a person's (or dog's) height. Not like IGF which determines if a dog breed is short or tall. So some people are tall because they have a lot of tall genes. Like basketball players. And others are shorter because they have fewer. Like jockeys. Even considering jockeys and basketball players, people are really the same size. Compared to dogs anyway.

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Most dogs in a breed are
about the same size.
People are like a single breed of dog.
Evolution can be quick
Domestic dogs originally descended from the gray wolf about 15,000 years ago. But gray wolves are all about the same size. So the extraordinary differences in dog size have all happened in the last 15,000 years. But, really, most dog breeds have come along in the past few hundred years. Now 300 years may seem like a long time to you. But to evolution, it's very short. Remember, humans descended from apes 5-8 million years ago. How did dogs gain such differences in size so quickly? We're not sure of the answer, but we have some guesses. They have to do with the way evolution works. And how people can accelerate the process. Evolution is how a population, like dogs, changes over time. For example, it's how dogs developed their tremendous size variation. In order to change or evolve, there must already be variation or differences in the population. These differences usually accumulate over time from errors when DNA is copying itself. They affect how well the population survives. For dogs, the differences in IGF (and probably other genes) developed after they descended from wolves. That's why wolves are all about the same size and dogs aren't. OK, so dogs had the potential to be big or small. Where did the breeds actually come from? Well, if they were in the wild, a dog's size would be determined by the environment. Let's say one group of dogs lives in a place with lots of rodents and not much else. Like the American plains without buffaloes. In that environment, little dogs would do best – those that have two small IGF alleles. These dogs would need less meat, could ferret the rodents out of their burrows, etc. There, the little dogs would be very successful and have lots of puppies. The big dogs wouldn't do as well. So over time, the little dogs would replace the big ones. Now imagine someplace with lots of deer. There, a dog needs to be big to bring down the deer. So the dogs with the two large IGF alleles would prosper. And big dogs would rule. As you can see, the environment determines which size dog survives better to have more puppies. And eventually take over the population. What people did was to speed up the process by becoming the environment. We decided which dogs would get to successfully breed. And which ones wouldn't. Because of this, we were quickly able to select for the traits we wanted. Dogs like dachshunds that were bred to go down badger holes. Or Australian shepherds bred to herd sheep. The mutations or SNPs in IGF (along with mutations in other genes) made the incredible size variation in dogs possible. And then we humans did the rest of the work! That's why all of these breeds could develop in a few hundred years. Instead of a few million. But the differences in dogs' DNA were key. Without them, dogs would all be the same size. Amy Radermacher