Selection is for the dogs

I was really pleased to see the new paper by Erik Axelsson and colleagues Axelsson:2013 on the pattern of recent selection on domesticated dogs. As we began working on recent selection in humans, we expected that domesticated animals might exhibit similar patterns genome-wide. They are among the organisms most similar to humans in demography and ecological change: Domesticated animals have all undergone rapid shifts in diet, predator ecology and social dynamics after domestication, at the same time that they have experienced rapid increases in population size. That is a recipe for rapid adaptive evolution.

As in humans, the paper shows that dogs were selected strongly for a new agricultural diet. Just as in humans who descend from early agriculturalists, dogs have extensive duplication of the amylase gene. Humans express amylase in saliva, but as explained in the paper dogs only produce amylase in the pancreas, where it digests starches intestinally. Where this paper gets really exciting is when the authors began to investigate the entire metabolic pathway underlying starch digestion. The amylase gene AMY2B underwent duplications similar to those in humans, and not found in wolves. Two other genes that interact in starch digestion and glucose uptake did not undergo duplication but do show near-fixed haplotypes in dogs that are absent or very rare in wolves, and the paper shows using both biochemistry and phylogenetic comparison with herbivores and omnivores that the dog versions of these genes increase enzymatic activity on starches and glucose uptake.

In conclusion, we have presented evidence that dog domestication was accompanied by selection at three genes with key roles in starch digestion: AMY2B, MGAM and SGLT1. Our results show that adaptations that allowed the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in early dog domestication. This may suggest that a change of ecological niche could have been the driving force behind the domestication process, and that scavenging in waste dumps near the increasingly common human settlements during the dawn of the agricultural revolution may have constituted this new niche6. In light of previous results describing the timing and location of dog domestication, our findings may suggest that the development of agriculture catalysed the domestication of dogs.

So for those of you wondering why we feed dogs kibble instead of raw beef, here's the reason.

After finding candidate regions for selection across the genome, the authors ran a gene ontology analysis to see whether functional gene loci in these regions fall into any consistent categories. Along with the metabolic and digestive genes, they found

The most conspicuous cluster (11 terms) relates to the term nervous system development. The eight genes belonging to this category (Supplementary Tables 7 and 8) include MBP, VWC2, SMO, TLX3, CYFIP1 and SH3GL2, of which several affect developmental signalling and synaptic strength and plasticity. We surveyed published literature and identified 11 additional CDR genes with central nervous system function (Supplementary Table 9), adding to a total of 19 CDRs that contain brain genes. These findings support the hypothesis that selection for altered behaviour was important during dog domestication and that mutations affecting developmental genes may underlie these changes7.

That is a similar story to humans. We don't know what such genes might do, and unraveling what difference these genes may have made to behavior will take a lot of additional understanding of developmental biology. Much easier to work out what is going on when you can examine the biochemistry in vitro as with starch enzymes.

The paper also makes clear why finding evidence of selection can be a difficult empirical problem at the moment:

Uniquely placed sequence reads from pooled DNA representing 12 wolves of worldwide distribution and 60 dogs from 14 diverse breeds (Supplementary Table 1) covered 91.6% and 94.6%, respectively, of the 2,385 megabases (Mb) of autosomal sequence in the CanFam 2.0 genome assembly11. The aligned coverage depth was 29.8 for all dog pools combined and 6.2 for the single wolf pool (Supplementary Table 1 and Supplementary Fig. 1). We identified 3,786,655 putative single nucleotide polymorphisms (SNPs) in the combined dog and wolf data, 1,770,909 (46.8%) of which were only segregating in the dog pools, whereas 140,818 (3.7%) were private to wolves (Supplementary Table 2). Similarly we detected 506,148 short indels and 26,619 copy-number variations (CNVs) (Supplementary Files 1 and 2). We were able to experimentally validate 113 out of 114 tested SNPs (Supplementary Table 3 and Supplementary Discussion, section 1).

If that sounds confusing, that's because it is confusing. Right now whole-genome sequencing is not yet routine, and whole-exome sequencing is not routine for creatures other than people. So maximizing the available data means working with partial genomes at varying levels of coverage, often accumulated for other purposes by other research groups using different sequencing platforms. Verifying sequence differences is not trivial. Generating a sample of gene sequences from many individuals is challenging, particularly as different individuals may be covered or not for different parts of their genomes.

Studying selection requires a fairly large sample of genomes. This paper establishes evidence of selection on a few things in which domesticated dogs are mostly the same, and all are different from wolves. In other words, these are "complete sweeps" or "near-complete sweeps", in which a new genetic variant has become mostly fixed within the domesticated dog sample. A larger sample of dogs would be able to test selection with a broader range of strength and initial date, including "partial sweeps" and selection on standing variation that may have already existed in ancestral wolves before being subject to selection in domesticated dogs. So this paper opens a new area of inquiry on the causes of domestication without ruling out that we will discover much, much more about the history of selection in dogs.

One really cool possibility is that we will uncover convergent or parallel patterns of selection in dogs with different geographic origins. Already we know that body size and pigmentation have been subject to selection in different dog breeds, and that single genes transferred across breeds have been important parts of that process. There are a few cases in humans where the extensive geographic dispersal of a single adaptive variant can explain the present distribution of a trait. But in many more cases, different human groups have attained traits by parallel selection on different genetic variants. Because humans control the breeding of dogs and traded dogs across long distances in historic times, we may find that dogs are much less affected by parallelism and much more by long-distance gene flow than humans. But we won't know until we put that hypothesis to the test.