There’s no single gene that determines dog size, according to Dr. Ostrander, a dog genomics expert at the National Institutes of Health. There are about 25. She and other scientists found the first known dog size gene, and one of the most significant, in 2007. It’s called IGF1. The importance of the gene has been confirmed in many studies. But how it affected size wasn’t clear.
“The thorn in my side,” Dr. Ostrander said, was that no one could find a mutation in the gene or the DNA stretches that controlled it to explain what the actual changes in DNA were that affected size. “It’s not an exon, it’s not a promoter. It’s not an enhancer. It’s not a splice site,” she said, referring to sections of DNA that control genes. “We couldn’t find it. And Joc (pronounced Joss) came on the scene.”
“And I found it,” he said, with a grin.
Dr. Plassais, who was working at the N.I.H. during the research and is now at the University of Rennes 1, in France, said he had the great good luck to be working at a time when so many genomes of dogs and other canids, modern and ancient, are available. So by comparing more than a thousand genomes from more than 200 different breeds, he found a DNA stretch that came in two versions, or variants, that were tied to size.
This bit of DNA is not a gene, because by definition a gene has to contain the instructions to make a protein. But many other stretches of DNA have the instructions for bits of RNA that help to control genes. He found a DNA stretch that has instructions for what is called anti-sense RNA, which plays a significant role in controlling the production of proteins specified by genes.
His find is called IGF1-AS and it comes in two variants. Each dog has two copies of this DNA. Two large variants make a big dog, like a German shepherd. Two small variants make a small dog, like a miniature schnauzer, and one of each make a medium-sized dog, like one of the ubiquitous dusty-colored village dogs seen around the world.