In the last post in this series, we looked at how artificial selection played an important role in Darwin’s conception of natural selection. One example of artificial selection that Darwin drew upon was the domestication of dogs – a process that has recently been greatly informed by genomics comparisons between dogs and their closest wild relatives, wolves.
(Slowly) becoming man’s best friend
The domestic dog has the distinction of being the only known animal to be domesticated by humans prior to the advent of agriculture. As such, dogs are not only man’s best friend in the animal kingdom, but also his oldest one. Though the precise origin of dogs was a mystery in Darwin’s day, Darwin drew on them as an example of artificial selection that would be familiar to his readers, since the practice of shaping breeds over time was familiar to his audience:
But when we compare the dray-horse and race-horse, the dromedary and camel, the various breeds of sheep fitted either for cultivated land or mountain pasture, with the wool of one breed good for one purpose, and that of another breed for another purpose; when we compare the many breeds of dogs, each good for man in very different ways… We cannot suppose that all the breeds were suddenly produced as perfect and as useful as we now see them; indeed, in several cases, we know that this has not been their history. The key is man’s power of accumulative selection: nature gives successive variations; man adds them up in certain directions useful to him. In this sense he may be said to make for himself useful breeds.
Note that Darwin is careful to point out that the variation itself is due to heredity: while humans can “add up” variation over time through selective breeding, they cannot produce the variation upon which they act. This point was important for Darwin to make, since he would later argue that natural selection also acts on that same heritable variation over time in a cumulative way.
Darwin’s use of dogs as an example was hindered, however, by his not knowing whether all dogs were descended from one ancestral species or if different breeds had been independently domesticated from different species. Darwin (erroneously, as we will soon see) suspected the latter, perhaps in part because of the dramatic morphological differences between dog breeds. He does, however, contemplate the possibility that some widely divergent dog breeds were derived from a common stock, and notes that, if demonstrated, such a finding would be significant evidence that “closely allied” species in nature were, in fact, related:
When we attempt to estimate the amount of structural difference between the domestic races of the same species, we are soon involved in doubt, from not knowing whether they have descended from one or several parent-species. This point, if it could be cleared up, would be interesting; if, for instance, it could be shown that the grey-hound, bloodhound, terrier, spaniel, and bull-dog, which we all know propagate their kind so truly, were the offspring of any single species, then such facts would have great weight in making us doubt about the immutability of the many very closely allied and natural species—for instance, of the many foxes—inhabiting different quarters of the world. I do not believe, as we shall presently see, that all our dogs have descended from any one wild species; but, in the case of some other domestic races, there is presumptive, or even strong, evidence in favour of this view…
The whole subject must, I think, remain vague; nevertheless, I may, without here entering on any details, state that, from geographical and other considerations, I think it highly probable that our domestic dogs have descended from several wild species.
As it turns out, Darwin was wrong on this point—we now know that all dog breeds are derived from only one wild species, the gray wolf (Canis lupis). Genome sequencing studies place dogs and gray wolves as extremely close relatives, which is hardly surprising, since they remain fully capable of interbreeding. Beyond establishing wolves as the closest wild relatives to dogs, genome comparisons are also beginning to reveal how human artificial selection brought dogs into being.
Teasing out the genetic basis for the domestication process has become increasingly possible now that the dog genome has been completely sequenced (published in 2005). This complete sequence allows for detailed comparisons between dogs and gray wolves, as well as comparisons between dog breeds. Both studies shed light on how artificial selection shaped dogs over their shared history with humans. Comparisons to wolves allow us to determine what selection steps took place during the early domestication process, whereas comparisons within breeds allow us to examine the selection steps that gave each breed its unique suite of characteristics.
From wolf to dog: the early domestication process
Though the wolf and dog genomes are overwhelmingly similar to one another, there are subtle differences between them. Recent research has sought to identify regions of the dog genome that were selected for during the domestication process. These regions are expected to show less variation than what is seen in the rest of the dog genome at large. Recall from our prior discussion that selection reduces the variation in a population by picking out certain variants and favoring their reproduction over others. As we scan through the dog genome, we can thus look for regions that show very little variation (i.e. all, or almost all, dogs have the same sequence in that area) in contrast to other regions where dogs, as a population, have more variation present. We can also then compare these putative selected regions with the wolf genome, to find the regions that not only have reduced variation within dogs but also differ from what we see in wolves (since we are interested in regions that contribute to the differences we see between wolves and dogs). Having found the regions of the dog genome that meet these criteria, it is then possible to examine the sorts of genes found in them, and generate hypotheses for why selection on those specific genes may contribute to the morphological and behavioral differences we observe.
The results of this analysis were striking in that the main category of genes found in such “candidate domestication regions” were genes involved in nervous system development and function. These results support the hypothesis that the primary focus of the early domestication process was selecting for behaviors, such as reduced aggression and willingness to submit to an altered, human-dominated social structure.
Small genetic changes add up
At both early stages of dog domestication (and as we will see, at later stages of breed creation), similar conclusions can be drawn: small changes at the genome level can have very large effects on morphology and behavior for the organism as a whole. We have discussed this point before in the context of comparing the human and chimpanzee genomes, and drawn the same conclusion—small perturbations to a complex system can effect substantial change over relatively “short” timescales. (By short, I mean short from a geological perspective.) Dogs and wolves have been in the process of separating for about 100,000 years, meaning that the dog domestication process and the subsequent creation of dog breeds occurs in a blink of an eye geologically speaking. If future paleontologists were to find a dachshund in the fossil record, it would seem to appear out of nowhere and have only a distant relationship to wolves, despite the fact that we know dogs and wolves are part of the same species (with all the inherent “fuzziness” that the term “species” entails).
Selection, artificial or natural, is selection
The power of artificial selection was a useful argument for Darwin in the 1850s, since it demonstrated the remarkable flexibility a species could have under differing selective environments, and revealed the inherent variation within populations that could be acted on to drive significant change over time. Here in the early 21st century we are beginning to see the genetic underpinnings of artificial selection at a genome-wide level, and the results are absolutely in keeping with Darwin’s ideas: that populations contain significant diversity, and that artificial selection can act on that diversity over time to promote the reproduction of certain variants over others, and thus shift average characteristics of a population. And just as Darwin drew parallels between artificial and natural selection, so to can we: the evidence we have suggests that natural selection acts in essentially the same way as artificial selection—by favoring the reproduction of certain variants over others.
In the next post in this series, we’ll examine how artificial selection shaped the creation of specific dog breeds, and examine how natural selection has also shaped the dog genome during the domestication process.
Is artificial selection a useful analogy for natural selection?
You will recall that Darwin presented examples of artificial selection as evidence that natural selection could produce the same effect on a species: a shift in average characteristics within a population over time. Darwin, of course, had no idea about how heredity worked. Now that we have access to genome sequences, however, we have the opportunity to test the strength of Darwin’s analogy at the molecular level. To do that, however, we need to compare the molecular details of both types of selection events. Interestingly, the dog genome also shows signs of natural selection during the early domestication process, which we can compare to examples of artificial selection.
Meat or potatoes? Natural selection during early dog domestication
The very same study (which we discussed yesterday) that demonstrated significant selection for variation in nervous system genes in dogs during the early domestication process also identified selection on a class of genes involved in starch metabolism. Starch is a long chain of sugar (glucose) molecules strung together that plants use as an energy storage mechanism. Wolves do not eat a diet with high amounts of starch, but do ingest some in the wild fruit they sometimes consume (e.g. berries). In order to benefit from starch, mammals use a class of enzymes called amylases that break the starch chain down into separate glucose molecules. In wolves, amylase is produced in the pancreas. Like wolves, dogs also have a pancreatic amylase enzyme—but instead of having just one gene, all modern dogs have between 2 and 15 copies of this gene, whereas all wolves have only one. The dog copies sit side-by-side in the dog genome, right next to where the original amylase gene is found in wolves, indicating that the gene copies were duplicated during chromosome replication. These extra amylase gene copies greatly increase the amount of amylase enzyme that dogs make compared to wolves, and allow dogs to benefit from a high-starch diet in a way that wolves never could.
This diet, of course, is a distinctly human diet: large-scale use of starchy plants is a feature of human agriculture, which comes on the scene about 10,000 years ago, give or take. The association of dogs with humans at this time thus seems to have provided a selective advantage to dogs that could derive more benefit from the food they were receiving (or scavenging) from human sources. In other words, the environment the dogs were in (access to high starch foods associated with proximity to human settlements) provided the selection: dogs that could derive increased nutritional benefit from starch would be able to reproduce at a greater frequency than dogs that could not. Over time, the average ability of dogs to metabolize starch would improve in the population, as more and more dogs would have duplications. Since no conscious human choice was made to identify dogs with duplicated amylase genes and select them for breeding (since the characteristic would not be readily observable) this is an example of environmental, or natural selection. Even today humans do not have the ability to select dogs for increased starch metabolism, despite the fact that modern dogs remain variable for the number of amylase gene copies they have.
From dog to dachshund: artificial selection for a new gene
Having domesticated wolves into dogs, our selective efforts didn’t stop there, of course: humans used artificial selection to create 400-plus dog breeds, and we can see the effects of this selection on the dog genome when we compare different breeds to one another. One striking example of a difference between breeds is leg length. Some breeds are defined by an unusually short leg without a proportional reduction in body size, such as in basset hounds and dachshunds. This trait, known by the technical term “chondrodysplasia,” is one that was selected for based on its utility for certain hunting roles, such as the pursuit of burrowing animals. The genetic basis of this trait turns out to be another duplication event that happened once within domestic dogs: all short leg breeds share the same genetic innovation.
Note: the molecular details of this duplication event are somewhat more complex than for the simple side-by-side duplications of the amylase gene that we have just discussed. I’ve included the details below for those readers who are interested in digging into the finer points. The take-home message, however, is simple: in this case, a new trait (shortened legs) came into being when a gene was duplicated and the copy acquired new properties during the duplication event. The shortened leg trait was noticed and intentionally selected for by human breeders, making this an example of artificial selection leading to breeds with a specific characteristic. If the details of the duplication event itself are not of interest, feel free to skip down and pick up the story under the “Comparing artificial and natural selection in dogs” heading.
The molecular basis of how this new gene responsible for chondrodysplasia in dogs came to be is very similar to something we have discussed in detail before: the new gene is in effect a processed pseudogene that acquired a function at the time of its duplication. Since the new copy was functional from the beginning, it is not best described as a pseudogene, but rather as a retrogene: the mRNA copy of a gene that was (a) reverse transcribed from mRNA back into DNA, (b) inserted into the genome next to sequences that could direct its expression, and (c) came under selection to maintain it:
The new retrogene turns out to be a copy of the fgf4 gene, an important regulator of growth and development. For reasons that are not yet clear, the fgf4 retrogene interferes with normal bone growth and causes the short leg trait in chondrodysplastic dogs:
Another interesting feature of the new fgf4 retrogene is that its regulatory sequence (shown in yellow in the figure above) is derived from a transposon. As we have discussed before, transposons are autonomous, self-replicating DNA parasites that can, on occasion, become part of the genes of their hosts – and this is another example. The new fgf4 retrogene is “cobbled together” from transposon sequences and the original fgf4 coding sequence and has a new function (attenuating leg growth) not seen in either the original fgf4 gene or the transposon sequence.
Comparing artificial and natural selection in dogs
While the mutation that led to shortened legs in some dog breeds is a particularly dramatic example of a new variation arising (since it involves the birth of what is effectively a new gene), there were many other genomic regions selected during the creation of dog breeds. Other, more mundane examples abound: the small body size common to the “toy dog” group is determined by selected variation in the Insulin-like growth factor 1 (IGF1) gene; variation in three key genes have been identified as responsible for coat color variation; and even variation in a gene that is responsible for the characteristic skin wrinkling seen in the Shar-Pei has been described. In these cases, it is not the production and selection of duplicated or new genes that is responsible for these traits, but rather small mutations in existing genes that alter the function of those genes compared to the ancestral state in wolves or early dogs. Again, the main theme is clear: small changes in DNA, combined with artificial selection, can add up to large changes in form within a population in a short amount of time.
So, how comparable are natural selection and artificial selection? Both forms of selection have the ability to shift average characteristics of a population over time. Additionally, the molecular underpinnings of the mutation events for both types of selection events are comparable: the trait must arise through a mutation that produces a new heritable variant in the population. Note well: in the case of artificial selection, human intelligence and agency cannot produce the variation needed, but only select for it once it arises. In both cases, we have examples of small sequence mutations, duplications, and even new genes arising. Indeed, the only difference is the selection step—the filter that allows some variants to reproduce preferentially over others.
Human agency might be an efficient form of selection, but so, too, is nature. As such, Darwin’s use of artificial selection as evidence for selection in nature remains a valid approach, even at the molecular level.
In the next post in this series, we’ll explore how natural selection has shaped amylase function in the human lineage as well as in dogs.