I recieved this via an email list. The only links I could come up with were behind a subscriber wall, so I”m reposting it here in its entirety. There is more in the extended entry – fascinating stuff for both the dog breeder and medically oriented. For dog breeders who have been following discussions raging around genetic diversity over the past few years (an offshoot of the environmental and animal rights cults), the findings about the frequency of new mutations undermines some old mythology that physical extremes in dog breeds are due to inbreeding.
Old tricks make new dogs
Dozens of new dog breeds have taught Dallas scientists one of evolution’s very old tricks. The researchers have uncovered a previously unappreciated genetic mechanism that, over millions of years, may have helped sculpt the many different shapes of the world’s animals.
The findings based on a gene that helps give dog breeds their distinctive head shapes may also explain how massive St. Bernards, tiny Chihuahuas and everything in between descended from the wolf in just a few thousand years.
Understanding this genetic process could also give scientists new clues to the development of the human form and brain, as well as the rampant growth of cancers.
“We’re just beginning to scratch the surface of all the gadgets and tools that nature has come up with,” said John “Trey” Fondon, one of the biologists from the University of Texas Southwestern Medical Center at Dallas who performed the new research. “This is just one of them. But what
it says is that we don’t know nearly what we think we know about how evolution works.”
Original Research Article here (pdf), courtesy of John Fondon.
The report describing the research, released Monday [12-13-04], appears online in the Proceedings of the National Academy of Sciences.
Several years ago, Dr. Fondon and UT Southwestern collaborator Harold “Skip” Garner began to study portions of the genetic blueprint that stood out from the rest. The genetic blueprint of all organisms exists in long chains of four DNA chemicals, abbreviated A, T, C and G. Embedded in those chains are series of the same letters, repeated over and over again, such as CAGCAGCAGCAGCAG.
The scientists noticed that many of these repeated series were smack in the middle of genes that instruct cells to make proteins important for sculpting the body’s form during an animal’s development.
Curious about whether different repeated lengths cause different body shapes, Dr. Fondon decided to investigate them in a species that encompasses a vast range of shapes — man’s best friend, the domestic dog.
92 breeds studied
Drs. Fondon and Garner used dogs — including their own pets — representing 92 breeds to obtain DNA from blood samples. The scientists then used a laser 3-D scanner to create computer models of dog skulls from the same breeds, loaned from museums in Alaska, Washington, D.C., Los
Angeles and Switzerland. Finally, they analyzed the repeated sequences in several genes and tried to make correlations between the length of the repeats (which varies among breeds) and the shapes of the dogs’ skulls.
The UT Southwestern scientists found that the number of repeats in a gene called Runx-2 correlates with the angle and length of a breed’s nose. For instance, bull terriers dogs with long, downturned snouts, typified by former Budweiser mascot Spuds McKenzie, had 13 repeats in a row. But the boxer, with a short and upturned nose, had 16 repeats.
The scientists concluded that the lengths of genetic repeats in all the dogs studied had to be a result of domestication and breeding because dogs had repeat lengths well outside the range in their ancestor, the wolf. That fits with the fact that the dog noses can be much shorter or much longer than wolf noses.
The findings also mean that established dog breeds continue to change — and new ones continue to appear — because breeders are creating new genetic material as they select dogs with the highly prized, more extreme physical traits.
Dr. Fondon suspects that along with head shape, many aspects of a breed’s appearance, including leg length, girth, tail type and overall size, may be due to variation in repeats found in key genes.
Conventional wisdom says all the traits seen in modern dogs were presentbut simply hidden in wolves, Dr. Fondon said.
“Our data shows that dogs are creating new variation all the time,” he said.
If scientists can figure out the genes that control other physical and behavioral traits, genetic tests for especially important traits may one day be available to dog breeders. A score on a genetic test could potentially help a breeder decide which pups to sell and which to breed, said Karl G. Lark, a biologist at the University of Utah in Salt Lake City.
The same mechanism that has allowed dog breeders to create new genetic variation may well apply to agriculture.
“Most of our understanding of agricultural breeding is that all these traits are hidden … that we tap into the variation that’s already there,” said Sean Carroll, an evolutionary and developmental biologist at the University of Wisconsin, Madison. “We thought we were tapping old mutations
and not creating new ones. But their evidence suggests that we’re creating new mutations.”
In fact, Dr. Fondon was able to document a genetic change in the bull terrier that appears to have occurred within the last 70 years. Early in the century, the bull terrier’s nose was shorter and less angled than noses of modern bull terriers. When Dr. Fondon analyzed DNA from tissue still attached to the skull of a bull terrier that died in 1931, he found that its Runx-2 gene had one more repeated unit than modern bull terriers.
Effect on evolution
Drs. Fondon and Garner suspect that the type of changes in gene repeats caused by dog breeding may have also been at work during evolution.
Lengthening or shortening gene repeats is an ideal way for evolutionary forces to alter an organism’s appearance because changes in the repeats occur often as DNA is passed from one generation to the next, Dr. Lark said. Other kinds of DNA changes are more rare.
In evolution, the changes due to stretching or shrinking the repeats probably haven’t been as extreme as those created by dog breeding, said Dr. Carroll of Wisconsin. When genes change, there can be multiple effects, some good and some bad. Pets pampered by their breeders can accommodate changes that animals in the wild probably could not.
“All sorts of trade-offs are accepted by breeders as they’ve gone for the traits they’ve desired,” Dr. Carroll said. “In the wild, those trade-offs would not necessarily be accepted.”
For instance, almost all English bulldogs have to be delivered by Caesarean section because breeders have opted for larger and larger heads. Such a trait would obviously not survive in the wild.
That fits with the Dallas researchers’ findings that the lengths of genetic repeats in wild animals fall in a much narrower range than the repeats in a domestic dog, Dr. Fondon said.
The repeats in the genes that sculpt dogs’ bodies are also present in genes that shape the human body, said Dr. Garner of UT Southwestern. People’s facial features, for example, may be connected to variations in the same genes. And, Dr. Garner said, the same kinds of repeats are also prominent in genes that help the brain develop and function, and in genes connected
with neurological disease.
The genetic repeats are also present — and change quickly — in key genes in cancer cells, possibly contributing to tumor growth. Scientists are just beginning to investigate the role of the genetic repeats in human disease.
“My opinion is that … repeats are playing major roles in a variety of different diseases and in evolution, and they’re far underappreciated,” Dr. Garner said.
The research’s ultimate effect on evolutionary biology remains to be seen, but Dr. Lark, of Utah, said he thinks researchers should pay attention.
“It’s not clear at this time how much of the evolutionary process will conform to [the] explanation,” he said. “But I’m convinced that [the] model will certainly be very important in future evolutionary thought.”