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One question that tugged at Swedish researcher Carles Vil is how dogs can have such a wide variety of phenotypesimagine a tiny Chihuahua standing next to a Great Dane, or a Chinese shar-pei peering from under its skin folds at an Old English sheepdog who peers back through its long hair. In fact, the variation among breeds of dogs is far greater than the variation among other completely distinct species in the family Canidae.! ! If dogs evolved from wolves, which seems to be the case, then wolves must have had the capacity for this diversity somewhere in their genomes. Thus, Vil and his colleagues decided to compare the mitochondrial DNA of dogs and wolves in an attempt to understand the genetic consequences of these species' di"erent lifestyles: domesticated versus wild. (Remember, both dogs and wolves evolved from a common ancestral wolf species, so wolves are an ideal control with which to study the consequences of dogs' life with humans.) The mitochondrial genome was used because of earlier work by Vil that showed the nuclear genomes of dogs and wolves to be too similar to study their molecular evolution. On the other hand, this research indicated that mitochondrial lineages are clearly distinguishable for the two species.! ! Vil hypothesized that certain mutationsthose that might be deleterious, but not strongly soaccumulated faster in populations in which natural selection had been relaxed, resulting in a decline in tness. In other words, after dogs started to live with humans, less t individuals were more likely to survive and reproduce than they were in the wild. In addition, it is highly likely that dogs were strongly selected for certain behavioral traits, such as tameness. "It is therefore possible that this process led to an increase in functional genetic diversity throughout the entire dog genome," wrote Vil, "including both genes and elements a"ecting gene expression." Such a relaxation of selective pressures might

have led to the wide phenotypic diversity in dogs, as well as the variety of diseases seen in dogs today.! ! ! The degree to which new mutations have played a role in the development of the modern dog still requires intense scrutiny, but three major sources of genomic variation have been proposed as contributors to the high levels of phenotypic variation observed in today's domestic dogs. The rst is variability associated with microsatellites or simple sequence repeats (SSRs). Fondon and Gardner hypothesized that repeat length polymorphisms, particularly those occurring in regulatory regions, were an important source of morphologic variation, in part because they occur at a mutation rate 100,000# greater than SNPs [20]. Their contention is supported by a comparison of repeat lengths between humans and dogs at 36 developmentally associated loci, which revealed signicant recent changes in the length of the dog alleles. When these same loci were compared amongst dog breeds, ve genes exhibited large repeat expansions or contractions. Among the more interesting was a polymorphism observed in Great Pyrenees within the coding sequence of the Alx-4 gene, which is postulated to be responsible for their characteristic rear digit polydactyly [20]. Four Great Pyrenees exhibiting rear digit polydactyly possessed the variant Alx-4 allele, while one Great Pyrenees who lacked rear digit polydactyly did not carry the variant allele [20].! ! ! http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000310! ! ! ! ! ! Inbreeding is the mating together of closely related dogs, for example mother/son, father/daughter and sibling/sibling matings. For breeders, it is a useful way of xing traits in a breedthe pedigrees of some exhibition dogs show that many of their forebears are closely related. For example, there is a famous cat by the name of Fan Tee Cee (shown in the 1960s and 1970s) who has appeared in more and more Siamese

pedigrees, sometimes several times in a single pedigree, as breeders were anxious to make their lines more typey. Superb specimens are always much sought-after for stud services or o"spring (unless they have already been neutered!), having won the approval of show judges.! ! However, inbreeding holds potential problems. The limited gene pool caused by continued inbreeding means that deleterious genes become widespread and the breed loses vigor. Laboratory animal suppliers depend on this to create uniform strains of animal which are immunodepressed or breed true for a particular disorder, e.g. epilepsy. Such animals are so inbred as to be genetically identical (clones!), a situation normally only seen in identical twins. Similarly, a controlled amount of inbreeding can be used to x desirable traits in farm livestock, e.g. milk yield, lean/fat ratios, rate of growth, etc.! ! ! Summary: Scientists or dog breeders can use DNA tests to study the ancestry of mix breed dogs.! ! ! !