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Lessons in Nutrigenetics: Amylase

I find the story of amylase to be quite interesting, partly because it's a less understood nutrigenetics story compared to lactase. To look at amylase, we must first understand it's substrate, starch.

Starch is the polysaccharide storage form of plants - it is homologous to human's storage of glucose as glycogen. Starches are made of two types of glucose polymers - amylose and amylopectin. The enzyme, amylase, is able to catalyze the hydrolysis of starch (at the interior positions), yielding maltose and maltotriose from amylose, and maltose, glucose and dextrins from amylopectin. These are further degraded by isomaltases to provide an energy substrate for the body.

Amylase provides a lot of insight into human evolution because of its varied copy number across human populations. 5 genes on Chromosome 1 encode for amylase: AMY1A,B,C and AMY2 A andB (1). AMY1 is our gene of interest, because of its increased copy number - It is believed that the human salivary amylase gene, AMY1, is the result of a gene duplication event, derived from the pancreatic amylase gene - there is a retroviral insertion upstream from the duplication event that contains a parotid (salivary) specific enhancer, ensuring tissue specificity (parotid vs pancreatic expression). There is only about a 3% sequence difference in the gene sequences for the parotid and pancreatic enzymes. This gene duplication event, which appears to have evolved independently of other mammals with salivary amylase (rat), occurred rather recently in the human lineage. Chimpanzees that have been analyzed contained, at most, 2 diploid AMY1 copies and bonobos are believed to have a disrupted coding sequence and produce no salivary amylase (2). Aside from an increase in AMY1 copy number between humans and chimpanzees, humans populations exhibit a wide range in AMY1 copy numbers. Most interestingly, populations who are traditionally more agriculture-based and have higher starch intake exhibit higher AMY1 copy numbers than those who have traditionally been more hunter-gatherer-forager. This would appear to be an example of the nutritional environment playing a selective role - the more starch a population eats, and the better able they are to digest the starch, the more reproductive success.

This story is far from complete, however. The lack of diversity found among the sequences for the salivary amylase genes indicates a rather recent event in human history, although more humans are needed to confirm this lack of heterogeneity. There's evidence to show that early hominid ancestors (see previous posts) were beginning to make use of starch-rich underground storage organs such as tubers - salivary amylase may have enhanced the bioavailability of calories from these food sources - I can picture an Australopithecean gnawing on tubers for a while and salivary amylase playing a distinct role.

When considering why/how/when this copy number was selected for, one must consider the source of starch, digestion time, the duration of time spent chewing and exposing food to saliva - salivary amylase has been shown to potentially persist through the stomach and intestines (3) - as well as discussing whether this gene duplication event occurred before or after the controlled use of fire.

 Salivary amylase may have also played a protective role against postprandial blood glucose levels - There is evidence to show (4) that salivary amylase copy number may affect glucose tolerance/clearance - Higher Amylase Gene Copy Number was associated with improved glycemic homeostasis compared to low copy number. This study that showed improved glucose tolerance provided results contrary to what was expected, only included 14 people, and the mechanism is only postulated (does AMY1 copy number affect some pre-insulin response??). Whether AMY1 copy number affects blood glucose levels is to be determined until a larger cohort is observed with the same effect. If it holds true, this could provide some interesting insight about the evolutionary history of starch consumption/digestion and it's role in health.

I find it an opportune time to point out that evolving to do something does not mean it is a necessity or that it will provide optimum health. We have clearly evolved to better utilize starch-rich plant organs as an energy substrate and this likely helped us to survive in some way, based off the apparent selection for AMY1 copy number in starch consuming populations. However, nutrition is toxicology - consuming what amount of these starches is ideal for modern health? Starches vary in nutrient density - think whole grains vs sweet potatoes vs unripened bananas - i'll advocate for sweet potatoes from a health perspective every time. Look at Celiac's disease - not everyone has evolved to eat starches. There is also the line of thinking that plant defense systems, while not powerful enough to play a modern selective role, may contribute to disease processes - this is still largely speculation. As pointed out in this review article, (5) the role of lectins in diseases, especially of autoimmune nature that interact with infectious disease, should be considered.

I'm excited to see where future AMY1 evolution research goes - it can provide a great insight into exactly how nutrition has effected evolution and even provide some biomedical implications for individuals/populations with different starch digestive capacity. 


1. Samuelson, L. et al. Retroviral and Pseudogene Insertion Sites Reveal the Lineage of Human Salivary and Pancreatic Amylase Genes from a Single Gene during Primate Evolution. Molecular and Cellular Biology. 1990.
2. Perry et al. Diet and the evolution of human amylase gene copy number variation
3. http://www.ncbi.nlm.nih.gov/pubmed/3652896
4. Mandel, A.  High Endogenous Salivary Amylase Activity is Associated with Improved Glycemic Homeostasis following Starch Ingestion in Adults. 2012. The Journal of Nutrition
5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1115436/

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