From extending lifespan to bolstering the immune system, the drug’s effects are only just beginning to be understood.
The selection of traits suitable for human companionship may have dragged along some unfavorable alleles.
December 21, 2015|
FLICKR, NICK FULLERTONTake the bad with the good, as they say. The domestication of wolves into dogs and the later diversification of dogs into breeds may have increased the number of harmful mutations that dogs carry in their genomes, according to research published today (December 21) in PNAS.
“The way in which certain breeds were created not only selected for traits that humans found desirable but it also saddled those breeds with a little bit more deleterious mutations than they would have had otherwise,” Joshua Akey, a geneticist at the University of Washington who was not involved in the work, told The Scientist.
Canines were first domesticated at least 15,000 years ago somewhere in Eurasia, and several evolutionary pressures could theoretically lead to a build-up of disadvantageous mutations as domestication proceeded, the authors wrote in their study. One of these factors is a reduction in population size, known as a population bottleneck, which hampers natural selection’s ability to remove harmful mutations.
“You have bottlenecks occurring essentially at least twice in the history of dogs,” said Kirk Lohmueller of the University of California, Los Angeles, who led the work. “First with domestication, more on the order of thousands of years ago, and then more recently with breed formation, on the order of a couple hundred years.”
Another relevant evolutionary force is positive selection, exemplified by breeders choosing to propagate particular traits, such as docility or coat color. The problem with positive selection is that if deleterious mutations happen to be near (or linked to) the gene variants under positive selection, they too can get passed along. This side effect of positive selection is called a selective sweep.
Researchers suspected that dog domestication would have resulted in an accumulation of deleterious mutations, but until now the hypothesis remained untested.
Lohmueller and colleagues analyzed sequence data from the genomes of 19 gray wolves, 25 semi-feral “village dogs” from 10 countries, and 46 breed dogs, representing dozens of breeds, and examined the genetic variation within each group. They looked for evidence of “deleterious” alleles, defined by an amino-acid change “at a phylogenetically conserved site”—one where evolution seemed to have favored a particular amino acid across the genomes of many vertebrates and where a change would likely be a mistake.
Overall, dogs had about 115 more deleterious alleles than wolves, or 2.6 percent more deleterious variants—a higher estimated “genetic load,” the researchers found. A greater genetic load is associated with lower reproductive fitness.
Lohmueller’s team also found that that, likely due to selective sweep, regions around genes that have undergone positive selection were enriched for disease-causing variants. For instance, in poodles, a gene involved in coat color (KIT Ligand) is linked to copy number variants that may lead to an increased risk of squamous cell carcinoma of the nail bed, according to an earlier report that the researchers cited in their study. Without selection for positive traits, they suspect, those disease-causing mutations might have been eliminated or reduced in frequency.
The small increase in dogs’ genetic load is probably not cause for dog-lover alarm, Lohmueller told The Scientist. It does imply, however, that “the strong selection for these breed-specific traits . . . may favor what’s sort of fashionable rather than necessarily functional or healthy,” he added.
Humans have domesticated many organisms, of course, and as is the case with dogs, their genomes also contain the untoward signatures of selective breeding. For example, “all crops were domesticated and they also have these effects,” said Brandon Gaut, an evolutionary geneticist at the University of California, Irvine, who has studied the genetics of domestication in maize and rice.
Lohmueller’s work has implications beyond pups and could help researchers better understand human evolution. Just as dogs passed through multiple population bottlenecks in their history, so humans have experienced reductions in population size as we left Africa and spread across the globe, explained Akey, who studies evolution in humans as well as in dogs. Whether or not the “out-of-Africa” bottleneck and others have led to increases in deleterious mutations in some human populations is “a pretty controversial topic,” he added. This paper “addresses a pretty similar topic in an organism that also has a pretty complex demographic history.”
C.D. Marsden et al., “Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs,” PNAS, doi:10.1073/pnas.1512501113, 2015.
Correction (December 21): The article originally stated that Brandon Gaut also studies sunflower domestication. The Scientist regrets the error.
December 22, 2015
This is really not complicated. Defective alleles are eliminated in wild wolf populations simply because wolves evolved a means of eliminating them; inbreeding. Defective alleles are filtered out with every generation. The alpha male and female are usually the only breeders in a real pack, unlike the pseudo packs the biologists created in the reintroductions to Yellowstone. These were actually gangs rather than packs. A typical alpha male and female will be as closely related as mother and son, unrelated wolves approaching the pack will usually be killed, but if accepted will not breed, hence no new genes are often imported. A litter may have several puppies but few survive, sometimes none, with the result that a pack becomes a stable unit of from 7 to 10 individuals, stable because it is an effective predator unit but not too big that a kill does not provide adequate nutrition of all individuals. Alpha selection is still mostly mysterious because observations in the wild are so difficult but phenotype selection appears to be a particularly significant issue. One rare observation in the wild identified a small new female who was the omega of the puppies of that year and not expected to survive the winter. However in the spring she turned out to have become the alpha female. Alpha selection appears to be a family affair and not a physical battle as witnessed in captive packs which are topically gangs of unrelated animals. In the wild an existing ageing alpha will pull back in favor of an offspring and change its dominance behavior. We can look at the pack as an apex predator which optimizes its survival rather than the individuals. Wolves having this evolved attribute were naturally equipped to cooperate with humans and exhibit pack loyalty. The human-dog hunting unit was a more effective apex predator then they were separately. The wolves can run down and corner prey but the actual kill is highly dangerous for them, however for the humans unable to chase down but able to kill at a distance the combination was unstoppable. The wolf phenotype evolved to embrace this relationship so certain attributes essential to a wolf pack become delegated to the human partner. Currently we are obsessed with genes as the foundation of everything but wolf and dog genes are much the same and the two can interbreed, producing confused animals because the two phenotypes are incompatible; they typically end up in cages at rescues. The wolf and dog phenotypes are differentiated through the programming of the genome, not particularly the genome itself. This is achieved partly through epigenetic changes, changes which we are increasingly discovering are, horror of horrors, heritable. The bottom line is that dogs have a tailored phenotype, each breed tailored for a particular purpose. For show dogs we want a placid dog that doesn’t think too much. For herding sheep we don’t much care about show points, we want a highly intelligent athlete. But this doesn’t mean we can’t take a hunting Golden Retriever line and then tailor it a quite different purpose; then do an about-face and turn it back into a hunting athlete. This takes several generations of course but what’s happening is not genetic mutation and natural selection but rapid adaptation of phenotype to current expectations. But dogs are not alone with a tailored phenotype, we humans have it too. How else could all of those millions of dogs have installed themselves in our homes unless our phenotype had generally evolved to make us willing victims