The origin of the short-legged breed

A single evolutionary event seems to be an explanation for the short and curved legs typical of all weasel dogs, Welsh dogs, dog dogs and at least 16 other dogs, a research group belonging to National Institute of Genome Research (NHGRI), National Institutes of Health, reported July 16. In addition, this unexpected finding provides new clues about how differences Physical appearance in the species and the introduction of new methods to understand a form of stunting in humans

In a study published in Science, researchers under the direction of NHGRI's Dr Elaine Ostrander analyzed DNA samples from 835 buffaloes, including 95 short-legged legs. The survey, which includes more than 40,000 markers of DNA modification , found a genetic marker only in short-legged dogs. Through computer analysis and DNA sequences later, the researchers determined that the dogs' short unbalanced legs originated from a single mutation event in the dog's genome - adding DNA - appeared very soon. in the evolution of domesticated dogs.

NHGRI director Dr. Eric Green said: 'All species, including dogs and humans, carry in themselves an astounding record of evolution within the genome, and possibly for us. know the mechanisms of action in biology, as well as health and disease in humans. This study provides surprising evidence for a new way in which genomic evolution works to diversify species. '

Specifically, the researchers found that in contrast to other breeds, all short-legged breeds have an additional version of the gene that promotes growth-promoting proteins called fibroblast growth factor 4. (FGF4). Despite normal operation, this extra gene lacks part of the DNA code called introns that can be found in normal genes. These characteristics led to the conclusion of the researchers that this gene is a retrogen that was introduced into the dog genome at some point after the ancestors of modern dogs separated from wolves.

To understand retrogene, we need to understand how cells make proteins. To produce a protein, a gene's DNA code is copied into a molecule called messenger RNA (mRNA). The mRNA leaves the nucleus of the cell and enters the outer area of ​​the cell, called the cytoplasm. There a small molecule, called a riboxome, reads information on mRNA and forms a protein.

Baxet dog (left) and mink dog. (Photo: National Institute of Genome Research)

Retrogenes are formed when the mRNA encounters an obstacle - usually a type of virus called a retrovirus - turning it back into DNA through a process called reverse transcription. This new DNA fragment, which contains the same protein-coding information as the gene that produced the mRNA, is then returned to the genome, often in a completely different position from the original gene. Depending on its location in the genome, this DNA fragment may or may not produce protein.If it works normally, the gene is called retrogene.

In the case of short-legged dogs, added retrogene causes too much FGF4 protein production. The researchers hypothesized that this phenomenon could activate growth receptors at inappropriate times during embryonic development. Veterinary researchers have known that in some dogs the development of long bones is shortened by calcification of growth plates, resulting in short legs and curved shapes. This feature, called unbalanced stunting, or cartilage disorder, is the standard of the Kennel Club for more than a dozen family dogs, including mink dogs, Welsh dogs, Peking dogs and dogs. baxet.

The study's lead author, Dr. Heidi G. Parker of NHGRI, said: 'Our findings suggest that retrogene may play a more important role in the evolutionary process, especially as a source. Specified skin species. We were surprised to find that only one retrogene introduced at one point in the evolution of a species created completely different chat characteristics preserved over time. '

In the past, retrogene has been identified as an important source of changes that stimulate species diversification. However, this discovery of dogs is the first example of a retrogene that makes a significant and lasting change to an animal.

This finding may also have implications for our understanding of human biology and pathology. Researchers stress that some people are affected by a similar growth disorder, called hypochondroplasia, which belongs to a group of conditions commonly known as stunting. While about two-thirds of hypochondroplasia are thought to be due to another gene, the cause of one-third of the remaining remains a mystery.

Dr. Ostrander, the lead author of the study currently working at NHGRI's Internal Research Unit, said: 'This study shows that a new gene needs to be thoroughly analyzed to understand the possible role in hypochondroplasia disease in humans. This study may well be important for scientists studying different aspects of human growth and development. '

In addition to Ostrander and colleagues at NHGRI, the team includes researchers from Cornell University in Ithaca, NY; University of California, Los Angeles; Oregon Medical and Science University, Portland; Waltham Animal Nutrition Center in Leicestershire, United Kingdom; and Affymetrix, Santa Clara, Calif.