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The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history

Picture of rice.

The emergence of agriculture about 10,000 years ago marks a dramatic change in human evolutionary history. The domestication of plants and animals caused major diet shift in recent human history. This diet shifts may create different selective pressures acting on the genetic variations of human populations. Two well-studied examples are the copy number variation of amylase gene for starchy food and the regulatory sequence variations of lactase for milk. In southern China, the earliest agriculture started to flourish due to the domestication of rice about 10,000 years ago. Hence, like the amylase gene selected for high copy numbers in agricultural societies including East Asia, the rice-culture-related selection could have been acting on populations living in southern China. Rice has been used as the material to produce fermented food and beverages for a long time in southern China since early Neolithic time. The fermentation helps to preserve and enhance the nutritional value of foods and beverages. However, alcohol can lead to addiction and cause damages to human bodies, including nervous system dysfunction, tumor genesis, innate immune system modulation and fetal alcohol syndrome. Therefore, genes involved in the ethanol metabolic pathway might become the target of selection when the ethanol-containing food and beverages had been routinely consumed by Neolithic populations in southern China.

The Class I alcohol dehydrogenase (ADH) is the major enzyme that catalyzes alcohol to acetaldehyde in liver. The Class I ADH genes (ADH1A, ADH1B, and ADH1C) encode three subunits of Class I ADH isoenzymes, i.e. a, b and g. ADH1BArg47His (rs1229984), a mutation located in ADH1B, changes of amino acid from Arg to His causes enzymatic activity alteration. The derived allele, ADH1B*47His, changes the pKa of the enzyme from 8.5 to 10.0 which is associated with 40 to 100 fold increase in Km and Vmax of alcohol metabolism. The molecular signature of positive selection on ADH1B have been reported. We hypothesize that the emergence and expansion of rice domestication during Neolithic time is the driving force, leading to the current regional distribution of the ADH1BArg47His polymorphism in East Asia. To test this hypothesis and find the source of selection, a team led by Professor Bing Su based at the Kunming Institute of Zoology, Chinese Academy of Sciences studied a total of 38 populations (2,275 individuals) including Han Chinese, Tibetan and other ethnic populations across China. The results showed a clear east-to-west cline of the ADH1B*47His allele distribution, this allele is dominant in south-eastern populations but rare in Tibetan populations. The molecular dating suggests that the emergence of the ADH1B*47His allele occurred about 10,000~7,000 years ago. This result presents genetic evidence of selection on the ADH1BArg47His polymorphism caused by the emergence and expansion of rice domestication in East Asia. The geographic distribution of the ADH1B*47His allele in East Asia is consistent with the unearthed culture relic sites of rice domestication in China. The estimated origin time of ADH1B*47His allele in those populations coincides with the time of origin and expansion of Neolithic agriculture in southern China. The results published in BMC Evolutionary Biology 2010, 10:15 ( Read comments by the ScienceNOW (


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