Dietary Variation and Evolution of Gene Copy Number among Dog Breeds

Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs.长期的人类互动与人工选择，塑造了各犬种间的基因型与表型多样性。由于人类与犬类栖息于多样生境，生态环境或推动了犬种特异性的正向选择。在现代犬类饲养方式出现以前，不同犬种的饮食谱或存在显著差异。据此，我们针对3个代谢基因中的一类遗传变异——拷贝数变异（copy number variation）展开研究，涉及的基因包括：葡萄糖激酶调节蛋白（glucokinase regulatory protein, GCKR）、植烷酰辅酶A 2-羟化酶（phytanol-CoA 2-hydroxylase, PHYH）以及胰腺α-淀粉酶2B（pancreatic α-amylase 2B, AMY2B）。上述基因编码的蛋白分别负责代谢源自三类截然不同食物的膳食产物：糖类、肉类与淀粉。在调研了不同饮食背景犬只的拷贝数变异情况后，我们发现GCKR与PHYH的正向选择均与饮食无相关性。尽管此前已有研究证实，在犬类驯化过程中或驯化完成后，犬类相较于狼的AMY2B拷贝数有所升高，但我们的研究表明，在驯化后的多个时期内，采食高淀粉饮食的犬种中，正向选择仍持续作用于淀粉酶拷贝数。此外，我们发现不同犬种AMY2B的正向选择衰退，并非由与狼的基因渐渗所致。综上，上述结果支持"淀粉酶拷贝数扩增普遍存在于犬类中"这一假说。