Caldwell, Elizabeth F. (2005) Molecular Evidence for Dietary Adaptation in Humans. Doctoral thesis, University College London.

Starch digestion begins in the mouth where it is hydrolysed into smaller polysaccharides by the enzyme salivary amylase. Three salivary amylase genes (AMY1A,B & C) and a psuedogene (AMYP1) have been described and are located in tandem on the short arm of chromosome 1. Polymorphic variation has been demonstrated in Caucasian populations in the form of the number of repeats of the AMY1 genes, as follows: (1A-1B-P1)n-1C. This variation results in differing levels salivary amylase enzyme production and, as a result, differences in the efficiency of starch digestion. It is suggested that an increase in salivary gene copy number may be an adaptation to high starch diets as a result of the adoption of agriculture. A reliable high-throughput PCR based method has been designed that utilises ABI GeneScan technology, to quantify AMY1 gene copy number and to type 6 microsatellite markers closely linked to the AMY gene cluster. Data have been collected for 14 human populations, with different histories of cereal agriculture and levels of starch in the diet. Data have also been collected on AMY1 gene copy number in 5 common chimpanzees (Pan troglodytes).

The AMY1 allele frequency difference (measured using FST) between the two most extreme populations, the Mongolians and Saami, was not an outlier on a distribution of 11,024 SNPs from the human genome. As the AMY1 locus does not appear to differ from the rest of the genome in terms of allele frequency difference between populations, genetic drift could not be ruled out as an explanation for the observed AMY1 allele frequency differences. The chimpanzee data suggest that the most frequent allele (AMY1*H1) in humans may not be the ancestral allele, as all chimpanzee chromosomes tested carried the AMY1*H0 allele. Furthermore, a powerful method for the analysis of intra-allelic variability at the AMY locus suggests that weak positive selection has occurred on the AMY*H1 allele. As a result, genetic drift could not be ruled out as an explanation for the observed AMY1 allele frequency difference among populations.

Alanine:glyoxylate aminotransferase (AGT) is an intermediary metabolic enzyme that is targeted to different organelles in different species. Previous studies have shown that there is a clear relationship between the organellar distribution of AGT and diet. Non-human primates show the herbivorous peroxisomal distribution of AGT. In humans a point mutation and insertion deletion polymorphism have been associated with peroxisome-to-mitochondria AGT mis-targeting. Data have been collected using a PCR/RFLP based method, in 11 human populations. In a comparison with FST values from 11,024 SNP loci, 94.5% of SNPs had a lower FST than a comparison of AGT allele frequencies for Saami and Chinese. This unusually high allele frequency difference between Chinese and Saami is consistent with the signature of positive selection driven by the unusually high meat content in the Saami diet.

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