Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R. et al. Diet and the evolution of human amylase gene copy number variation. Nat. Genet. 39, 1256-1260

School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona 85287, USA.
Nature Genetics (Impact Factor: 29.35). 11/2007; 39(10):1256-60. DOI: 10.1038/ng2123
Source: PubMed


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.

Download full-text


Available from: Fernando A Villanea,
  • Source
    • "Structural variations with a net gain or loss of genetic material are called copy number variations (CNVs). Some insertions have been found to be present from 1 to 15 times in one genome compared to the reference one [5]. Some authors report approximately 28,000 unique CNVs, several of which are common among human populations [6] [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Copy number variant (CNV) regions have been proven to have a significant impact on gene expression. Some of them have been also found to be associated to different human diseases. CNV genotyping is often prone to error and cross-validation with independent methods is frequently required. The platform of choice depends on whether it is a genome-wide discovery screening or a candidate CNV study, the cohort size and the number of CNVs included in the assay and, finally, the budget available. Here we illustrate a affordable approach to determine the CNV genotype using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and based on the quantitative determination of single nucleotide duplicated mismatches (SNDM) mapping the CNV region and a paralogue genomic region that is used as a two-copy reference. We have genotyped nsv436327, a common CNV mapping SIRPB1 intron 1 that has been associated to human personality behavior. SIRP cluster region was subjected to several ancestral duplication events what makes SIRPB1 CNV genotyping technically challenging. We designed three sets of primer pairs that amplified paralogue regions inside and outside the CNV, containing three SNDMs. Post-PCR extension analyses of sequencing oligonucleotides mapping immediately upstream each SNDM allowed us to quantify using MALDI-MS the proportion of PCR products derived from the CNV region versus the external reference. In contrast to other approaches, setting up this genotyping method requires an affordable investment. Copyright © 2015. Published by Elsevier Ltd.
    Molecular and Cellular Probes 07/2015; DOI:10.1016/j.mcp.2015.07.009 · 1.85 Impact Factor
  • Source
    • "The chopped tuber and added water were transferred to a stomacher bag and combined with 50 ml warm water (408C) and 1000 U a-amylase (Sigma A1031) per 100 g tuber sample. This level of amylase activity was selected to approximate the estimated protein expression level for Hadza derived from a regression of the work of Perry et al. (2007) in their Fig. 1C and Supporting Information Table 1. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Bioaccessibility is a useful measure for assessing the biological value of a particular nutrient from food, especially foods such as tubers. The wild tubers exploited by Hadza foragers in Tanzania are of interest because they are nontoxic, consumed raw or briefly roasted, and entail substantial physical barriers to consumers. In this study, we attempted to elucidate the biological value of Hadza tubers by measuring the absorption of glucose through in-vitro digestion. Methods We quantified digestibility using data from 24 experimental trials on four species of Hadza tuber using a dynamic in-vitro model that replicates digestion in the stomach and small intestine. Analysis of glucose in the input meal and output dialysate revealed the accessible glucose fraction. We also conducted assays for protein, vitamin, and mineral content on whole tubers and meal fractions. Results Bioaccessibility of glucose varies depending on tuber species. Holding effects of chewing constant, brief roasting had negligible effects, but high intraspecific variation precludes interpretive power. Overall, Hadza tubers are very resistant to digestion, with between one- and two-thirds of glucose absorbed on average. Glucose absorption negatively correlated with glucose concentration of the tubers. Conclusions Roasting may provide other benefits such as ease of peeling and chewing to extract edible parenchymatous tissue. A powerful factor in glucose acquisition is tuber quality, placing emphasis on the skill of the forager. Other nutrient assays yielded unexpectedly high values for protein, iron, and iodine, making tubers potentially valuable resources beyond caloric content.
    American Journal of Physical Anthropology 07/2015; 158(3). DOI:10.1002/ajpa.22805 · 2.38 Impact Factor
  • Source
    • "Cold Spring Harbor Laboratory Press on August 19, 2015 -Published by Downloaded from the amylase genes have been suggested to be a result of adaptation to a starch-rich diet in human populations (Perry et al. 2007) and dogs (Axelsson et al. 2013). However, the genes analyzed in these studies (i.e., the salivary gene Amy1 and the pancreatic gene Amy2b) are not part of the duplications in our study, and we are currently investigating alternative interpretations for the pattern observed in this region (M Linnenbrink and D Tautz, in prep.). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Copy number variation represents a major source of genetic divergence, yet the evolutionary dynamics of genic copy number variation in natural populations during differentiation and adaptation remain unclear. We applied a read depth approach to genome resequencing data to detect copy number variants (CNVs) ≥1 kb in wild-caught mice belonging to four populations of Mus musculus domesticus. We complemented the bioinformatics analyses with experimental validation using droplet digital PCR. The specific focus of our analysis is CNVs that include complete genes, as these CNVs could be expected to contribute most directly to evolutionary divergence. In total, 1863 transcription units appear to be completely encompassed within CNVs in at least one individual when compared to the reference assembly. Further, 179 of these CNVs show population-specific copy number differences, and 325 are subject to complete deletion in multiple individuals. Among the most copy-number variable genes are three highly conserved genes that encode the splicing factor CWC22, the spindle protein SFI1, and the Holliday junction recognition protein HJURP. These genes exhibit population-specific expansion patterns that suggest involvement in local adaptations. We found that genes that overlap with large segmental duplications are generally more copy-number variable. These genes encode proteins that are relevant for environmental and behavioral interactions, such as vomeronasal and olfactory receptors, as well as major urinary proteins and several proteins of unknown function. The overall analysis shows that genic CNVs contribute more to population differentiation in mice than in humans and may promote and speed up population divergence. © 2015 Pezer et al.; Published by Cold Spring Harbor Laboratory Press.
    Genome Research 07/2015; 25(8). DOI:10.1101/gr.187187.114 · 14.63 Impact Factor
Show more