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Delving into our 10 million-year relationship with booze

| August 17, 2018
booze
This article or excerpt is included in the GLP’s daily curated selection of ideologically diverse news, opinion and analysis of biotechnology innovation.

For many years, the conventional academic wisdom was that the human love affair with alcohol began only 10,000 years ago, with the invention of agriculture. But research now suggests that this complicated relationship—associated with so much pleasure and pain and good health and death and good cheer and bar fights—actually began more than 10 million years ago. It was a gift, or curse, from the primate ancestors of chimps, gorillas and us.

Drinking was, in a sense, the human outcome of a war between plants and the creatures that must consume them to live, according to science journalist Faye Flam. Plants started making toxic substances like alcohols as a strategy to avoid being eaten. Animals started making chemicals that could detoxify those substances so they could go on eating.

One group of those defensive chemicals is the alcohol dehydrogenases (ADH), animal enzymes that break down the various alcohols produced by plants. Researchers based at institutions in Gainesville, FL earlier reported that about 10 million years ago our primate ancestors evolved a form of alcohol dehydrogenase, ADH4, that could metabolize ethanol, a common form of alcohol and the one that has led to so much pleasure and woe.

We humans have 7 ADH genes clustered together on chromosome 4, including the gene that appears to have started it all, ADH4. Many variants of the ADH genes contribute to alcohol dependence and other alcohol related traits, according to researchers at North Carolina State University in Raleigh.

ADH4′s job is to produce the enzyme that converts ethanol to acetaldehyde, and it’s actually acetaldehyde that’s mostly responsible for both the rewards and punishments of drinking alcohol. (It’s the cause of hangovers, for instance.) Acetaldehyde is broken down further by the aldehyde dehydrogenase gene family, ALDH. There are 18 ALDH genes, but only one, ALDH2, appears to be important to the history of human drinking.

Genes that protect against alcohol

ALDH2 is responsible for a phenomenon you may have heard about: the Asian flush or Asian glow.

The back of an Asian man experiencing alcohol flush. Credit: James Heilman, MD
The back of an Asian man experiencing alcohol flush. Credit: James Heilman, MD

The ALDH2*2 gene variant, found in about a third of East Asians (Chinese, Koreans, and Japanese), leads to a deficiency of this enzyme. It is associated with unpleasant reactions to alcohol. In addition to facial flushing, they include low blood pressure, headaches, and nausea. This discomfort is believed to provide protection against alcoholism in these populations.

Gregory Cochran briefly discussed evolution of protection against alcohol via the ALDH2 variant and includes a very nice map showing population distribution of this allele in Asia. It is impressively dense in China. He noted that populations with little historical exposure to alcohol–hunter-gatherers, especially–have high rates of alcoholism.

Cochrane didn’t mention this, but his meditation on how a population’s lack of experience with alcohol seems to lead to bad outcomes with it does imply that experience might eventually result in evolution of helpful protective mechanisms like the ALDH2 gene variant. This is unmitigated speculation, but I can’t help wondering if the antiquity of Chinese drinking has something to do with the appearance of this protective variant in China. The first archaeological evidence of drinking was discovered in China and has been dated at more than 9000 years ago.

True, 9000 years isn’t an awfully long time for evolution to work its natural selection magic. But it’s happened that fast—and faster—with other human genes that we know of. Prime example: the various gene mutations that permit several populations to drink milk successfully, which I discussed here at GLP last spring.

Related article:  'Drink like there is tomorrow': Inside the quest to prevent hangovers with a GMO probiotic

Despite the fact that Native Americans are, in a manner of speaking, of Chinese descent, the protective ALDH2 gene does not appear among them. Which is not so surprising if we’re theorizing that the mutation happened relatively recently in China, probably after agriculture made it possible for people to produce large amounts of alcohol. Native American forebears left Asia well before 10,000 years ago.

There’s at least one other protective gene, an ADH gene variant, ADH1B*2, found mostly in East Asians and Polynesians. Apparently it breaks alcohol down much faster than other versions of the ADH1B enzyme.

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Evolution of technology and alcohol genes

The Florida researchers said the appearance of the gene that started it all, ADH4, happened around the time primates began to descend from their treed life to walk the earth. This was a result of ecosystem changes that had begun transforming African forests into grasslands around 10 million years ago. Adapting to their new life on the ground, these primates expanded their diets from fresh ripe fruit collected while still on the trees to include fallen fruits. This new kind of foraging added nutrition, but if the fruit had started to ferment, it added a bit of alcohol too.

The researchers observed, “any organism with metabolic adaptations that permit the exploitation of ethanolic food would have access to a specialized niche or important fallback foods unavailable to organisms without this metabolic capacity.” They also noted that the small amount of alcohol in fermenting fruit is “a source of ethanol that is remarkably similar in concentration and form (i.e., with food) to the moderate ethanol consumption now recognized to be healthy for many humans.”

One theory about alcoholism and other ills related to consuming ethanol is thatlike diabetes and chronic cardiovascular disease—it’s one more manifestation of how, for most people except perhaps for some fortunate Asians, evolution hasn’t yet caught up with our lifestyles. Once agriculture began, wine and beer emerged as ways of storing surplus fruit and grain, and also gave pleasure.

The problems began when toolmaking Homo saps developed technology for fermenting larger amounts of fruits and grains into larger amounts of ethanoland then drank the larger amounts. Those problems were much compounded when alcohol distillation was invented less than a thousand years ago. Distillation takes a fermented beverage and gets rid of much of the water that dilutes it. That increases the alcohol content, sometimes greatly. Beer and wine typically contain less than 10 percent alcohol. In the US, vodka must by law be at least 40 percent alcohol.

A version of this story originally ran on the GLP on Nov. 15, 2016.

Tabitha M. Powledge is a long-time science journalist. She also writes On Science Blogs for the PLOS Blogs Network. Follow her @tamfecit 

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

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