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Why Asians don't get drunk

Gene Expression
By Razib Khan
Apr 2, 2008 10:31 AMNov 5, 2019 9:28 AM


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A new paper in PLOS One, Ethnic Related Selection for an ADH Class I Variant within East Asia:

The alcohol dehydrogenases (ADH) are widely studied enzymes and the evolution of the mammalian gene cluster encoding these enzymes is also well studied. Previous studies have shown that the

ADH1B*47His allele at one of the seven genes in humans is associated with a decrease in the risk of alcoholism and the core molecular region with this allele has been selected for in some East Asian populations.

As the frequency of ADH1B*47His is highest in East Asia, and very low in most of the rest of the world, we have undertaken more detailed investigation in this geographic region. ... The selection distribution is more significantly correlated with the frequency of the derived ADH1B regulatory region polymorphism than the derived amino-acid altering allele ADH1B*47His. Thus, the real focus of selection may be the regulatory region. The obvious ethnicity-related distributions of ADH1B diversities suggest the existence of some culture-related selective forces that have acted on the ADH1B region.

The authors don't think that selection was alcohol related as such; rather:

However the decrease in the risk for alcoholism has not been argued to be the selective force, and our results argue that selection is not solely related to ADH1B*47His. The derived promoter allele may have led to the increase of the ADH enzyme expression, and then enhance the protection against some deleterious effects. The ADH variants are also related to some types of cancers and other serious diseases...Infectious disease is one of the plausible selective forces suggested by Goldman & Enoch...Other diseases such as food poisoning can also have similar effects, and the populations will be susceptible if they happen to be partial to certain foods....

And actually, the protective allele is found outside of East Asia, from Geographically Separate Increases in the Frequency of the Derived ADH1B*47His Allele in Eastern and Western Asia:

The ADH1B Arg47His polymorphism has been convincingly associated with alcoholism in numerous studies of several populations in Asia and Europe. In a review of literature from the past 30 years, we have identified studies that report allele frequencies of this polymorphism for 131 population samples from many different parts of the world. The derived ADH1B*47His allele reaches high frequencies only in western and eastern Asia. To pursue this pattern, we report here new frequency data for 37 populations. Most of our data are from South and Southeast Asia and confirm that there is a low frequency of this allele in the region between eastern and western Asia.

The distribution suggests that the derived allele increased in frequency independently in western and eastern Asia after humans had spread across Eurasia.

Sound familiar? Kind of reminds me of skin color. In any case, the paper just published is reminiscent of the HERC2 and blue eye research which was buzzing a few months back. You have a really salient phenotype which might have been produced by selection for some other trait which we are unaware of (I think it's skin color for eye color). With all the genome wide scans picking out locus after locus I think we might get a sense that a lot of the normal variation we see around us is due to side effect for other traits which are extremeley fitness salient. Note: The title was tongue-in-cheek; I am well aware of the drinking culture in Korea & Japan for example. Update:Kambiz has more.

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