The alchohol dehydrogenase (ADH) gene family has seven members expressed in different organs and tissues; ADH1B is expressed mostly in the liver and lungs , where most alchohol is dehydrogenated . Therefore, ADH1B can be considered the most important member of the ADH family, and has become one of the most studied model genes for natural selection [3, 4] among the human genes. A single nucleotide polymorphism (SNP), ADH1B Arg48His (rs1229984), results in large functional differences in the respective enzymes of the ancestral and derived alleles. The enzyme catalytic activity of the derived allele is 40 times that of the ancestral allele . Thus, this SNP has been found to be relevant to cancers of the digestive and respiratory systems, alcoholism, addiction, and many other disorders [6–10].
The allele frequency of ADH1B*48His varies greatly among the world’s populations. The derived allele reaches high frequency only in eastern East Asia and Southwest Asia and is almost absent in the rest of the world . Further study revealed that several SNPs in ADH1B form different haplotypes, and haplotypes with the ADH1B*48His allele are different in East Asia and Southwest Asia , with evidence in East Asia of strong positive natural selection [11, 12] during the history of agriculture . In western East Asia, the allele frequency of ADH1B*48His is not high , especially among Tibetans . Tibetans share very recent common ancestors with the Han Chinese. Important questions are whether the ADH1B*48His alleles of Tibetans and Han Chinese have a common origin and, if so, why the frequency of this allele did not rise in Tibetans as it did in Han Chinese.
Our previous study found seven haplogroups (H1 to H7) for ADH1B among the world populations  based on seven SNPs in the gene. The ADH1B*48His allele appears in H5, H6, and H7. H5 is a Southwest Asian haplogroup. H6 derived from a crossover involving H5 and occurs primarily in East Asia and the Pacific region. H7 is derived from H6 by the addition of the derived allele of rs3811801 in the regulatory region of ADH1B. The age of H6 is about 15,000 to 21,000years , which is about the age of the modern East Asians [15–17]. Expansion of H7 happened only about 2,800 years ago, and is the only haplogroup with a strong signal of selection . The frequency of H7 is much higher in Han Chinese than the frequency of H6 [12, 18]. No study has previously investigated the distribution of the ADH1B haplogroups in Tibetan populations.
The languages of the Tibetans and Han Chinese belong to the Sino-Tibetan linguistic family. DNA evidence generally supports the hypothesis that populations speaking similar languages have recent common ancestors, especially in East Asia [19–21]. Y-chromosome DNA analyses argue that the divergence of Han Chinese and Tibeto-Burman populations was no earlier than 6,000 years ago [20, 22, 23].
There are five populations living in Tibet: Tibetans; Sherpa;Monba;Lhoba; and Deng . The Tibetans are the major population of Tibet, divided into three major branches, Weizang in central Tibet, Amdo in the north, and Khams in the east. Two minor Tibetan populations, Tingri and Gongbo, are yet to be classified into the three branches. Monba, Lhoba, and Deng are all in southeast Tibet. Their languages are mostly in the North Assam branch of Tibeto-Burman, while three-quarters of the Monba people use dialects mixed with the Tibetan language. The Sherpa people live in the middle of the Himalayas, an area overlapping with China, Nepal, Sikkim, and Bhutan, and speak a language very close to Tibetan . In this paper, we investigated Class I ADH and ADH7 haplogroup diversity among all populations in Tibet, and examined the diversity and selection signal of ADH1B.