AMY1 Copy Number Research Articles

The roles of AMY1 copies and protein expression in human salivary α-amylase activity

Salivary α-amylase (sAA) activity has been extensively investigated in nutrition and psychology. But few studies were performed to assess the role played by sAA gene (AMY1) copies and protein expression in basal and stimulus-induced sAA activity. The sAA activity, amount and AMY1 copy number were determined from 184 saliva samples pre- and post-citric acid stimulation. Our findings showed that citric acid could induce significant increase in sAA activity, total sAA amount, and glycosylated sAA amount, among which the glycosylated sAA amount had the largest response. The correlation analysis showed that AMY1 copy number, total sAA amount and AMY1 copy number×total sAA amount had significantly positive and successively increasing correlations with sAA activity in unstimulated and stimulated saliva, respectively, and furthermore, we observed higher correlations in unstimulated saliva when compared with the corresponding correlations in stimulated saliva. We also observed significant correlations between glycosylated sAA amount and sAA activity in unstimulated and stimulated saliva, respectively. Interestingly, the correlations were higher in stimulated saliva than in unstimulated saliva, and the correlations between glycosylated sAA amount and sAA activity were higher than that of between total sAA amount and sAA activity in stimulated saliva. Moreover, total sAA amount ratio and glycosylated sAA amount ratio showed significantly positive correlation with sAA activity ratio. AMY1 copy number had no correlation with sAA activity ratio. These findings suggested that AMY1 copy number and sAA amount played crucial roles in sAA activity; however, the roles were attenuated after stimulation due to fortified release of glycosylated sAA.

Low copy number of the salivary amylase gene predisposes to obesity

Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.

Lactase persistence and augmented salivary alpha-amylase gene copy numbers might have been selected by the combined toxic effects of gluten and (food born) pathogens

Various positively selected adaptations to new nutrients have been identified. Lactase persistence is among the best known, conferring the ability for drinking milk at post weaning age. An augmented number of amylase gene (AMY1) copies, giving rise to higher salivary amylase activity, has been implicated in the consumption of starch-rich foods. Higher AMY1 copy numbers have been demonstrated in populations with recent histories of starchy-rich diets. It is however questionable whether the resulting polymorphisms have exerted positive selection only by providing easily available sources of macro and micronutrients. Humans have explored new environments more than any other animal. Novel environments challenge the host, but especially its immune system with new climatic conditions, food and especially pathogens. With the advent of the agricultural revolution and the concurrent domestication of cattle came new pathogens. We contend that specific new food ingredients (e.g., gluten) and novel pathogens drove selection for lactase persistence and higher AMY gene copy numbers. Both adaptations provide ample glucose for activating the sodium glucose-dependent co-transporter 1 (SGLT1), which is the principal glucose, sodium and water transporter in the gastro-intestinal tract. Their rapid uptake confers protection against potentially lethal dehydration, hyponatremia and ultimately multiple organ failure. Oral rehydration therapy aims at SGLT1 activity and is the current treatment of choice for chronic diarrhoea and vomiting. We hypothesize that lifelong lactase activity and rapid starch digestion should be looked at as the evolutionary covalent of oral rehydration therapy.

Measurements of salivary alpha amylase and salivary cortisol in hominoid primates reveal within-species consistency and between-species differences.

Salivary alpha amylase (sAA) is the most abundant enzyme in saliva. Studies in humans found variation in enzymatic activity of sAA across populations that could be linked to the copy number of loci for salivary amylase (AMY1), which was seen as an adaptive response to the intake of dietary starch. In addition to diet dependent variation, differences in sAA activity have been related to social stress. In a previous study, we found evidence for stress-induced variation in sAA activity in the bonobos, a hominoid primate that is closely related to humans. In this study, we explored patterns of variation in sAA activity in bonobos and three other hominoid primates, chimpanzee, gorilla, and orangutan to (a) examine if within-species differences in sAA activity found in bonobos are characteristic for hominoids and (b) assess the extent of variation in sAA activity between different species. The results revealed species-differences in sAA activity with gorillas and orangutans having higher basal sAA activity when compared to Pan. To assess the impact of stress, sAA values were related to cortisol levels measured in the same saliva samples. Gorillas and orangutans had low salivary cortisol concentrations and the highest cortisol concentration was found in samples from male bonobos, the group that also showed the highest sAA activity. Considering published information, the differences in sAA activity correspond with differences in AMY1 copy numbers and match with general features of natural diet. Studies on sAA activity have the potential to complement molecular studies and may contribute to research on feeding ecology and nutrition.

Individual Differences in AMY1 Gene Copy Number, Salivary α-Amylase Levels, and the Perception of Oral Starch

BackgroundThe digestion of dietary starch in humans is initiated by salivary α-amylase, an endo-enzyme that hydrolyzes starch into maltose, maltotriose and larger oligosaccharides. Salivary amylase accounts for 40 to 50% of protein in human saliva and rapidly alters the physical properties of starch. Importantly, the quantity and enzymatic activity of salivary amylase show significant individual variation. However, linking variation in salivary amylase levels with the oral perception of starch has proven difficult. Furthermore, the relationship between copy number variations (CNVs) in the AMY1 gene, which influence salivary amylase levels, and starch viscosity perception has not been explored.Principal FindingsHere we demonstrate that saliva containing high levels of amylase has sufficient activity to rapidly hydrolyze a viscous starch solution in vitro. Furthermore, we show with time-intensity ratings, which track the digestion of starch during oral manipulation, that individuals with high amylase levels report faster and more significant decreases in perceived starch viscosity than people with low salivary amylase levels. Finally, we demonstrate that AMY1 CNVs predict an individual's amount and activity of salivary amylase and thereby, ultimately determine their perceived rate of oral starch viscosity thinning.ConclusionsBy linking genetic variation and its consequent salivary enzymatic differences to the perceptual sequellae of these variations, we show that AMY1 copy number relates to salivary amylase concentration and enzymatic activity level, which, in turn, account for individual variation in the oral perception of starch viscosity. The profound individual differences in salivary amylase levels and salivary activity may contribute significantly to individual differences in dietary starch intake and, consequently, to overall nutritional status.

Diet and the evolution of human amylase gene copy number variation.

Starch consumption is a prominent characteristic of agricultural societies and hunter-gatherers in arid environments. In contrast, rainforest and circum-arctic hunter-gatherers and some pastoralists consume much less starch. This behavioral variation raises the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis. We found that copy number of the salivary amylase gene (AMY1) is correlated positively with salivary amylase protein level and that individuals from populations with high-starch diets have, on average, more AMY1 copies than those with traditionally low-starch diets. Comparisons with other loci in a subset of these populations suggest that the extent of AMY1 copy number differentiation is highly unusual. This example of positive selection on a copy number-variable gene is, to our knowledge, one of the first discovered in the human genome. Higher AMY1 copy numbers and protein levels probably improve the digestion of starchy foods and may buffer against the fitness-reducing effects of intestinal disease.

The Non-Thrifty Genotype

Previous articleNext article No AccessReportsThe Non-Thrifty GenotypeJohn S. Allen, and Susan M. CheerJohn S. Allen Search for more articles by this author , and Susan M. Cheer Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Current Anthropology Volume 37, Number 5Dec., 1996 Sponsored by the Wenner-Gren Foundation for Anthropological Research Article DOIhttps://doi.org/10.1086/204566 Views: 5Total views on this site Citations: 20Citations are reported from Crossref Copyright 1996 The Wenner-Gren Foundation for Anthropological ResearchPDF download Crossref reports the following articles citing this article:Catalina I. Fernández, Andrea S. Wiley Rethinking the starch digestion hypothesis for AMY1 copy number variation in humans, American Journal of Physical Anthropology 163, no.44 (Jun 2017): 645–657.https://doi.org/10.1002/ajpa.23237Anna L. Gosling, Hallie R. Buckley, Elizabeth Matisoo-Smith, Tony R. Merriman Pacific Populations, Metabolic Disease and ‘Just-So Stories’: A Critique of the ‘Thrifty Genotype’ Hypothesis in Oceania, Annals of Human Genetics 79, no.66 (Sep 2015): 470–480.https://doi.org/10.1111/ahg.12132Stephen Corbett, Laure Morin-Papunen The Polycystic Ovary Syndrome and recent human evolution, Molecular and Cellular Endocrinology 373, no.1-21-2 (Jul 2013): 39–50.https://doi.org/10.1016/j.mce.2013.01.001Steve Ferzacca Diabetes and Culture, Annual Review of Anthropology 41, no.11 (Oct 2012): 411–426.https://doi.org/10.1146/annurev-anthro-081309-145806Staffan Lindeberg Paleolithic diets as a model for prevention and treatment of western disease, American Journal of Human Biology 24, no.22 (Jan 2012): 110–115.https://doi.org/10.1002/ajhb.22218Staffan Lindeberg Modern Human Physiology with Respect to Evolutionary Adaptations that Relate to Diet in the Past, (Jan 2009): 43–57.https://doi.org/10.1007/978-1-4020-9699-0_4Barnet Pavao-Zuckerman Deerskins and Domesticates: Creek Subsistence and Economic Strategies in the Historic Period, American Antiquity 72, no.11 (Jan 2017): 5–33.https://doi.org/10.2307/40035296Daniel C. Benyshek, James T. Watson Exploring the thrifty genotype's food-shortage assumptions: A cross-cultural comparison of ethnographic accounts of food security among foraging and agricultural societies, American Journal of Physical Anthropology 131, no.11 (Jan 2006): 120–126.https://doi.org/10.1002/ajpa.20334Josef Schmidhuber, Prakash Shetty The nutrition transition to 2030. Why developing countries are likely to bear the major burden, Food Economics - Acta Agriculturae Scandinavica, Section C 2, no.3-43-4 (Sep 2005): 150–166.https://doi.org/10.1080/16507540500534812Peter M. Nilsson Gene/Environment Interaction, (Jan 2005): 101–108.https://doi.org/10.1016/B978-84-8174-892-5.50006-1Staffan Lindeberg Palaeolithic diet (“stone age” diet), Scandinavian Journal of Nutrition 49, no.22 (Dec 2016): 75–77.https://doi.org/10.1080/11026480510032043Leslie Sue Lieberman Diabetes Mellitus and Medical Anthropology, (Jan 2004): 335–353.https://doi.org/10.1007/0-387-29905-X_40Leslie Sue Lieberman D IETARY , E VOLUTIONARY, AND M ODERNIZING I NFLUENCES ON THE P REVALENCE OF T YPE 2 D IABETES, Annual Review of Nutrition 23, no.11 (Jul 2003): 345–377.https://doi.org/10.1146/annurev.nutr.23.011702.073212Tessa M. Pollard Western Diseases, 57 (Jun 2012).https://doi.org/10.1017/CBO9780511841118Susan M. Cheer, John S. Allen, Judith Huntsman Lactose digestion capacity in Tokelauans: A case for the role of gene flow and genetic drift in establishing the lactose absorption allele in a Polynesian population, American Journal of Physical Anthropology 113, no.11 (Jan 2000): 119–127.https://doi.org/10.1002/1096-8644(200009)113:1&lt;119::AID-AJPA11&gt;3.0.CO;2-6Katharine Milton Hunter-gatherer diets—a different perspective, The American Journal of Clinical Nutrition 71, no.33 (Mar 2000): 665–667.https://doi.org/10.1093/ajcn/71.3.665Staffan Lindeberg, Mats Eliasson, Bernt Lindahl, Bo Ahrén Low serum insulin in traditional pacific islanders—The Kitava study, Metabolism 48, no.1010 (Oct 1999): 1216–1219.https://doi.org/10.1016/S0026-0495(99)90258-5Timothy Johns The Chemical Ecology of Human Ingestive Behaviors, Annual Review of Anthropology 28, no.11 (Oct 1999): 27–50.https://doi.org/10.1146/annurev.anthro.28.1.27John L. Brooke Domestication, Agriculture, and the Rise of the State, (): 109–120.https://doi.org/10.1017/CBO9781139050814.020John L. Brooke Human Well-Being from the Paleolithic to the Rise of the State, (): 213–242.https://doi.org/10.1017/CBO9781139050814.008