HGNC Approved Gene Symbol: AMY1B
Cytogenetic location: 1p21.1 Genomic coordinates (GRCh38): 1:103,687,415-103,696,453 (from NCBI)
Salivary alpha-amylase (EC 3.2.1.1) is a monomeric calcium-binding enzyme that initiates starch digestion in the oral cavity. The alpha-amylase enzymes are produced by the salivary glands (encoded by the AMY1A (104700), AMY1B, and AMY1C genes), and exocrine pancreas (encoded by the AMY2A (104650) and AMY2B (104650) genes). Additionally, a small amount of alpha-amylase is expressed by the AMY2B gene in the liver. The salivary alpha-amylase protein contains 511 amino acids with a 15-residue signal peptide (summary by Santos et al., 2012).
By in situ hybridization combined with high resolution cytogenetics, Zabel et al. (1983) assigned the amylase gene to 1p21, the POMC gene (176830) to 2p23, and the somatostatin gene (182450) to 3q28.
Using amylase DNA probes in somatic cell hybrids, Tricoli and Shows (1984) mapped the amylase genes to the 1p22.1-p21 region.
Gumucio et al. (1988) isolated cosmid clones containing 250 kb of genomic DNA from the human amylase gene cluster. These clones were found to contain 7 distinct amylase genes: 2 pancreatic amylase genes, 3 salivary amylase genes, and 2 truncated pseudogenes. Intergenic distances of 17 to 22 kb separated the amylase gene copies.
To investigate the genomic organization of the human alpha-amylase genes, Groot et al. (1989) isolated the pertinent genes from a cosmid library constructed of DNA from an individual expressing 3 different salivary amylase allozymes. From the restriction maps of the overlapping cosmids and a comparison of these maps with the restriction enzyme patterns of DNA from the donor and family members, they were able to identify 2 haplotypes consisting of very different numbers of salivary amylase genes. The short haplotype contained 2 pancreatic genes, AMY2A and AMY2B, and 1 salivary amylase gene, AMY1C, arranged in the order 2B--2A--1C, encompassing a total length of approximately 100 kb. The long haplotype spanned about 300 kb and contained 6 additional genes arranged in 2 repeats, each one consisting of 2 salivary genes, AMY1A and AMY1B, and a pseudogene lacking the first 3 exons, AMYP1. The order of the amylase genes within the repeat was 1A--1B--P1. All of the genes were in a head-to-tail orientation except AMY1B, which had the reverse orientation with respect to the other genes.
Polymorphism of both the salivary and the pancreatic serum amylases has been demonstrated in man. Ward et al. (1971) studied amylase in saliva and identified electrophoretic variants.
Pronk et al. (1982) presented evidence they interpreted as indicating duplication of the salivary amylase locus.
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
Large-scale copy number variations (LCVs) involve gains or losses of several kilobases to hundreds of kilobases of genomic DNA among phenotypically normal individuals. To investigate LCVs in the human genome, Iafrate et al. (2004) applied array-based comparative genomic hybridization (array CGH) to the genomes of 55 unrelated individuals. The most common LCV (identified in 49.1% of the individuals studied) encompassed the AMY1A and AMY2A locus (Groot et al., 1991). Iafrate et al. (2004) detected relative gains (in 23.6% of cases) and losses (in 25.5% of cases) at this locus and confirmed the array CGH results using metaphase-interphase FISH, high-resolution fiber FISH, and quantitative PCR. In all they described more than 200 LCVs in the human genome. Twenty-four of these variants were present in more than 10% of the individuals studied, and 6 of these variants were present at a frequency of more than 20%. A chromosome map indicating the location of the LCVs was provided. Carter (2004) commented on this work and the parallel work of Sebat et al. (2004).
Using a combination of high-precision measurement methods with segregation analysis, Carpenter et al. (2015) determined that most amylase haplotypes worldwide contain odd numbers of AMY1 repeat units, but that haplotypes carrying even numbers of AMY1 repeats are associated with rearrangements giving rise to CNV of the pancreatic amylase genes AMY2A/2B. As a consequence, the copy numbers of AMY1 and AMY2A/2B are numerically correlated. Data from different paralog ratio tests (PRTs) led to the experimental and read-depth characterization of 4 distinct CNV classes affecting AMY2 genes: a deletion of about 75 kb affecting AMY2A (and AMY1); a duplication of about 116 kb including both AMY2A and AMY2B (and a copy of AMY1); higher-order expansions of AMY2A and AMY2B; and an independent duplication of AMY2A but not AMY2B. Among the regional population groupings used by the 1000 Genomes Project, East Asian populations display few AMY2 variations and nearly all individuals have an even AMY1 diploid copy number; deletions of AMY2 are common among the European and American samples, and duplications of AMY2A/2B are at highest frequency in African samples.
Groot et al. (1990) presented structural analyses of the human amylase gene cluster that allowed them to construct a model for the evolution of this family of genes by a number of consecutive events involving inter- and intrachromosomal crossovers.
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 raised the possibility that different selective pressures have acted on amylase, the enzyme responsible for starch hydrolysis. Perry et al. (2007) found that copy number of the AMY1 gene 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 suggested that the extent of AMY1 copy number differentiation is highly unusual. 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.
Carpenter, D., Dhar, S., Mitchell, L. M., Fu, B., Tyson, J., Shwan, N. A. A., Ynag, F., Thomas, M. G., Armour, J. A. L. Obesity, starch digestion and amylase: association between copy number variants at human salivary (AMY1) and pancreatic (AMY2) amylase genes. Hum. Molec. Genet. 24: 3472-3480, 2015. [PubMed: 25788522] [Full Text: https://doi.org/10.1093/hmg/ddv098]
Carter, N. P. As normal as normal can be? (Comment) Nature Genet. 36: 931-932, 2004. [PubMed: 15340426] [Full Text: https://doi.org/10.1038/ng0904-931]
Groot, P. C., Bleeker, M. J., Pronk, J. C., Arwert, F., Mager, W. H., Planta, R. J., Eriksson, A. W., Frants, R. R. The human alpha-amylase multigene family consists of haplotypes with variable numbers of genes. Genomics 5: 29-42, 1989. [PubMed: 2788608] [Full Text: https://doi.org/10.1016/0888-7543(89)90083-9]
Groot, P. C., Mager, W. H., Frants, R. R. Interpretation of polymorphic DNA patterns in the human alpha-amylase multigene family. Genomics 10: 779-785, 1991. [PubMed: 1679752] [Full Text: https://doi.org/10.1016/0888-7543(91)90463-o]
Groot, P. C., Mager, W. H., Henriquez, N. V., Pronk, J. C., Arwert, F., Planta, R. J., Eriksson, A. W., Frants, R. R. Evolution of the human alpha-amylase multigene family through unequal, homologous, and inter- and intrachromosomal crossovers. Genomics 8: 97-105, 1990. [PubMed: 2081604] [Full Text: https://doi.org/10.1016/0888-7543(90)90230-r]
Gumucio, D. L., Wiebauer, K., Caldwell, R. M., Samuelson, L. C., Meisler, M. H. Concerted evolution of human amylase genes. Molec. Cell. Biol. 8: 1197-1205, 1988. [PubMed: 2452973] [Full Text: https://doi.org/10.1128/mcb.8.3.1197-1205.1988]
Iafrate, A. J., Feuk, L., Rivera, M. N., Listewnik, M. L., Donahoe, P. K., Qi, Y., Scherer, S. W., Lee, C. Detection of large-scale variation in the human genome. Nature Genet. 36: 949-951, 2004. [PubMed: 15286789] [Full Text: https://doi.org/10.1038/ng1416]
Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R., Werner, J., Villanea, F. A., Mountain, J. L., Misra, R., Carter, N. P., Lee, C., Stone, A. C. Diet and the evolution of human amylase gene copy number variation. Nature Genet. 39: 1256-1260, 2007. [PubMed: 17828263] [Full Text: https://doi.org/10.1038/ng2123]
Pronk, J. C., Frants, R. R., Jansen, W., Eriksson, A. W., Tonino, G. J. M. Evidence for duplication of the human salivary amylase gene. Hum. Genet. 60: 32-35, 1982. [PubMed: 6176528] [Full Text: https://doi.org/10.1007/BF00281260]
Roychoudhury, A. K., Nei, M. Human Polymorphic Genes: World Distribution. New York: Oxford Univ. Press (pub.) 1988.
Santos, J. L., Saus, E., Smalley, S. V., Cataldo, L. R., Alberti, G., Parada, J., Gratacos, M., Estivill, X. Copy number polymorphism of the salivary amylase gene: implications in human nutritional research. J. Nutrigenet. Nutrigenomics 5: 117-131, 2012. [PubMed: 22965187] [Full Text: https://doi.org/10.1159/000339951]
Sebat, J., Lakshmi, B., Troge, J., Alexander, J., Young, J., Lundin, P., Maner, S., Massa, H., Walker, M., Chi, M., Navin, N., Lucito, R., and 9 others. Large-scale copy number polymorphism in the human genome. Science 305: 525-528, 2004. [PubMed: 15273396] [Full Text: https://doi.org/10.1126/science.1098918]
Tricoli, J. V., Shows, T. B. Regional assignment of human amylase (AMY) to p22-p21 of chromosome 1. Somat. Cell Molec. Genet. 10: 205-210, 1984. [PubMed: 6608795] [Full Text: https://doi.org/10.1007/BF01534909]
Ward, J. C., Merritt, A. D., Bixler, D. Human salivary amylase: genetics of electrophoretic variants. Am. J. Hum. Genet. 23: 403-409, 1971. [PubMed: 5097906]
Zabel, B. U., Naylor, S. L., Sakaguchi, A. Y., Bell, G. I., Shows, T. B. High-resolution chromosomal localization of human genes for amylase, proopiomelanocortin, somatostatin, and a DNA fragment (D3S1) by in situ hybridization. Proc. Nat. Acad. Sci. 80: 6932-6936, 1983. [PubMed: 6196780] [Full Text: https://doi.org/10.1073/pnas.80.22.6932]