Starch digestion, stress, and human evolution

While reading a great Smithsonian article on the history of potatoes, I began thinking about a recent lecture I gave in my human genetics class at UAF. A copy number variation reading referenced human variation in amylase copy number. Amylase is an enzyme used to catalyze the digestion of starches into sugars and our reading indicated variation in the copy number for the AMY1A gene may play an interesting role in human evolutionary history.

Humans produce different isoforms of alpha amylase in saliva and the pancreas. During mastication of starchy foods (such as the potato), amylase begins to break the starch into glucose and maltose. (This causes activation of sweet taste receptors.) A paper by Perry et al. (2007) reported finding variation in CNVs for amylase that had an apparent correlation to diet. The authors tested variation in human populations with low (Biaka and Mbuti, Datog, and Yakut) and high (Europeans, Japanese, Hadza) starch diets  and cross-tested these findings on non-human primates. While our close Pan relatives (chimps and bonobos) and New World Monkeys had low copy numbers (expected due to high fruit consumption), starch consuming primates (some Old World Monkeys) had high copy number. The authors propose this emerged early in our hominin lineage and allowed us to diversify our diet beyond reliance on sugar-rich foods (e.g., fruits) to include starchy plants. But, low levels of nucleotide sequence divergence (compared to chimps) suggest a more recent origin for the CNV; however, testing more human groups for variation may push this date back. Positive selection arguments include:

First, a significant amount of starch digestion occurs in the mouth during mastication¹⁴. For example, blood glucose levels have been shown to be significantly higher when high-starch foods such as corn, rice, and potatoes (but not apples) are first chewed and then swallowed, rather than swallowed directly¹⁵. In addition, it has been suggested that oral digestion of starch is critically important for energy absorption during episodes of diarrhea⁴. Diarrheal diseases can have a significant effect on fitness; for example, such diseases caused 15% of worldwide deaths among children younger than 5 years as recently as 2001¹⁶. Lastly, salivary amylase persists in the stomach and intestines after swallowing¹⁷, thereby augmenting the enzymatic activity of pancreatic amylase in the small intestine. Higher AMY1 copy number and a concomitant increase in salivary amylase protein level are therefore likely to improve the efficiency with which high-starch foods are digested in the mouth, stomach, and intestines, and may also buffer against the potential fitness-reducing effects of intestinal disease.

This variation among and within human groups generates interesting questions relative to nutrition and starch intake. Firstly, those with increases in copy numbers are more efficient at digesting and this leads to perceptual variation in starch viscosity, which in turn may influence starch intake. As suggested in the Perry article, increased amylase production may confer an advantage to reproductive fitness in evolutionary history and episodes of weaning diarrhea. But, in modern populations, increased/rapid starch digestion has obvious links to diabetes and obesity. Indeed, a diabetic individual does not have sufficient insulin to catalyze starches after a meal and suffers negative health consquences. Anti-amylases (e.g., white beans) aid in slowing this process by blocking the enzyme and allowing the limited insulin in the system process simple sugars first.

A final note to consider is the potential use of elevated amylase as a stress test. Some studies have found an increased production of salivary amylase in response to stressful situations (physical or psychological). A review of these studies finds there much work to be done but argue that perhaps an explanation for the short-term increases may be part of the flight/fight response:

short-term increases may be useful to the body in that energy is made available by increased digestive action in response to stress. Physiological stress reactions comprise orchestrated actions throughout the body, putting the organism in a state of overall preparedness to engage in fight or flight. Thus, increases in amylase activity may be one of many actions involved in activating the body’s resources to cope with stressful events or threats to homeostasis. However, this explanation applies only to reactions to short-term, acute stressors. Further studies are needed to examine long-term changes in sAA concentrations.

In light of the potential population specific CNV, any alpha amylase test would have to be carefully designed to account for human variation. Certainly, the linkages between a resource-stressed environment and increased production of amylase have potential fascinating paleo-physiological connections even without an increase in copy number.