Diet and the evolution of human amylase gene copy number variation

Abstract

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 1-3 . This behavioral variation raises the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis 4 . We found that salivary amylase gene (AMY1) copy number is correlated positively with salivary amylase protein levels, 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 level of AMY1 copy number differentiation is unusual. This example of positive selection on a copy number variable gene is one of the first in the human genome. Higher AMY1 copy numbers and protein levels likely improve the digestion of starchy foods, and may buffer against the fitness-reducing effects of intestinal disease. Hominin evolution is characterized by significant dietary shifts, facilitated in part by the development of stone tool technology, the control of fire, and most recently the domestication of plants and animals 5-7 . Starch, for instance, has become an increasingly prominent component of the human diet, particularly among agricultural societies 8 . It stands to reason, therefore, that studies of the evolution of amylase in humans and our close primate relatives may provide insight into our ecological history. Because the human salivary amylase gene (AMY1) shows extensive variation in copy number 9,10 , we first assess whether a functional relationship exists between AMY1 copy number and the level of amylase protein expression in

Expansion of a 12-kb VNTR containing the REXO1L1 gene cluster underlies the microscopically visible euchromatic variant of 8q21.2

“…42 The 8q21.2 VNTR is one of the nine autosomal tandem arrays 42 kb that contain a single gene and show CNV. 27 Three of these nine have been associated with one or more traits including (1) higher copy number of the salivary amylase gene (AMY1) at 1q21.1 with high starch diets; 43 (2) increasing copy number of the 8p23.1 beta defensin genes with higher predisposition to psoriasis, 5,6 higher human immunodeficiency virus (HIV) load 7 and, possibly, resistance to influenza virus infection; 8 and (3) lower copy number of the CCL3L1 gene at 17q21.1 with weak protection against malarial anaemia 44 and susceptibility to chronic hepatitis C virus (HCV) infection. 45 It is therefore interesting that immunological reaction against the human REXO1L1 gene product (GOR) is a marker of HCV infection including occult HCV in which antibody assays against the HCV are negative.…”

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

“…This is likely an unrealistic scenario in human populations, where positive selection is perhaps less common (Hernandez et al 2011). However, some have argued that selection may be pervasive in the human genome as well (Boyko et al 2008;Enard et al 2014), and certainly humans show many adaptations to local environments (e.g., Li et al 2007;Perry et al 2007;Tishkoff et al 2007;Barreiro et al 2008;Bryk et al 2008). Thus while it seems unlikely that every site in the genome would be affected by linked selection, some currently unknown subset of sites must be, and thus we should expect demographic estimation to be subject to some degree of bias (perhaps negligible in well-designed studies; see below).…”

Implications of gene copy-number variation in health and diseases

“…It has been reported that higher copy number of AMY1 gene is correlated positively with salivary amylase protein levels and a population with high-starch food consumption has higher copy number of AMY1 gene and improves the digestion of starchy foods and may reduce the burden of intestinal diseases. 59 CNV AND DRUG METABOLISM Cytochrome P450 (CYP450) is a superfamily of hemoproteins involved in metabolism of xenobiotics such as clinically used drugs, procarcinogens and environmental pollutants.…”