Rethinking the starch digestion hypothesis for AMY1 copy number variation in humans

Abstract

Alpha-amylase exists across taxonomic kingdoms with a deep evolutionary history of gene duplications that resulted in several α-amylase paralogs. Copy number variation (CNV) in the salivary α-amylase gene (AMY1) exists in many taxa, but among primates, humans appear to have higher average AMY1 copies than nonhuman primates. Additionally, AMY1 CNV in humans has been associated with starch content of diets, and one known function of α-amylase is its involvement in starch digestion. Thus high AMY1 CNV is considered to result from selection favoring more efficient starch digestion in the Homo lineage. Here, we present several lines of evidence that challenge the hypothesis that increased AMY1 CNV is an adaptation to starch consumption. We observe that α- amylase plays a very limited role in starch digestion, with additional steps required for starch digestion and glucose metabolism. Specifically, we note that α-amylase hydrolysis only produces a minute amount of free glucose with further enzymatic digestion and glucose absorption being rate-limiting steps for glucose availability. Indeed α-amylase is nonessential for starch digestion since sucrase-isomaltase and maltase-glucoamylase can hydrolyze whole starch granules while releasing glucose. While higher AMY1 CN and CNV among human populations may result from natural selection, existing evidence does not support starch digestion as the major selective force. We report that in humans α-amylase is expressed in several other tissues where it may have potential roles of evolutionary significance.

Human amylase gene copy number variation as a determinant of metabolic state

“…Furthermore, when compared to other primates which consume lower amounts of starch, humans appear to possess higher AMY1 copy number [21,25,41] and express higher levels of salivary amylase [25]: for example, chimpanzees do not demonstrate AMY1 CNV at all, possessing only one copy per chromosome [25,42], and the quantity of salivary amylase produced by humans is around 6-8 times greater [25,43]. Although gorillas and bonobos do exhibit CNV [21,25,38], humans have a higher copy number than the former [38] and the latter's AMY1 copies may not be functional [25]. This difference in CNV largely reflects their respective diets: while gorillas may have a high starch intake [44], chimpanzees consume very little compared to the majority of human populations [25,45].…”

“…A clue originates from the observation of a positive correlation between CNV within AMY1 and the concentration and activity of salivary amylase in humans: increased copies of AMY1 presumably result in increased production and activity of salivary amylase, thereby facilitating initiation of amylase digestion within the saliva [14,15,18,21,25,[28][29][30][31]. Although pancreatic amylase accounts for most of digestion of starch within the diet, the role of salivary amylase in starch digestion should not be under-estimated [32].…”

“…Resulting products are broken down into absorbable free glucose by enzymes within the brush border of the ileum [18]. Small amounts of amylase are also produced by the liver [13, 19-21], nervous system, mammary tissue, uterus and testes [21].…”

“…It is well established that human salivary and pancreatic amylase genes manifest remarkable CNV [22][23][24][25]. Within an individual genome, there may be between 1-27 copies of AMY1 [21], 0-8 copies of AMY2A [26,27] and 2-6 copies of AMY2B [27]. However, the potential implications of amylase gene CNV for BMI and metabolic function have only become apparent in recent years.…”

Evaluation of commercial α‐amylase enzyme‐linked immunosorbent assay (ELISA) test kits for wheat

“…a-Amylase is widely distributed throughout the animal, plant, fungal, and bacterial kingdoms (Fernandez & Wiley, 2017;Lai, Jin, Kubelka, & Liberles, 2012;Møller, Henriksen, & Svensson, 2016). In humans, a-amylase genes are present in two paralogous groups: AMY1 (salivary) and AMY2 (pancreatic).…”