The holidays are packed with opportunities to raise a glass of our favorite boozy beverages and toast family, friends and good fortunes. But our ability to digest rum-spiked eggnog may be due to a massive climate shift that occurred millions of years ago. Using the tools of paleogenetics, scientists have recently traced the evolutionary history of an enzyme that helps us metabolize ethanol, the principal type of alcohol found in adult beverages. Scientists believe early human ancestors evolved their ethanol-digesting ability about 10 million years ago to fortify their diet as they shifted from a tree-based lifestyle to a more ground-based lifestyle.

Ancestral Alcohol

Researchers were hoping to shed light on when, exactly, human ancestors acquired the ability to consume foods containing ethanol, such as fermented fruits. Attempts to answer this question have yielded wildly divergent theories. One theory holds that primates regularly ingested ethanol some 80 million years ago as plants started producing fleshy fruits that could drop and ferment on the ground. Other scientists believe humans started enjoying ethanol just 9,000 years ago when we learned how to ferment foodstuffs. To help narrow that range, researchers studied the genetic evolution of alcohol-metabolizing enzyme ADH4, which has been present in primates, in one form or another, for at least 70 million years. Using genetic sequences from 28 different mammals, including 17 primates, the researchers were able to work backward and create a sort of family tree for ADH4. To see how the past versions would have worked, researchers then synthesized nine different ADH4 proteins and tested their ethanol-busting properties. Nearly all of the ADH4 enzymes from our primate ancestors were inactive — meaning they didn’t break down ethanol. However, about 10 million years ago, when orangutans and human ancestors diverged, things changed dramatically. A single amino acid alteration made ADH4 able to metabolize ethanol 40 times better than before.

Turning Point

This genetic switch to alcohol tolerance occurred at roughly the same time as apes moved from the trees to the ground. A period of rapid environmental change was putting pressure on ancient species, as forest ecosystems transitioned to grasslands. The timing leads researchers to suspect that an ability to digest alcohol was a benefit for our ancestors, who had to find ground-level food sources. Fallen fruit that began to ferment and produce ethanol could be poisonous to primates that couldn't digest it. Therefore, our ability to metabolize ethanol, researchers say, may trace back to our ancestors' taste for fermented foods. The results appear today in Proceedings of the National Academy of Sciences.

There's still more to learn — metabolizing ethanol is a complicated process involving an orchestra of enzymes. ADH4 is just one component of the process. Researchers would like to study the evolution of other ethanol-metabolizing enzymes to paint a more complete picture of humans’ relationship with the intoxicating substance. But one thing seems clear — this holiday season we'll be partaking in a very ancient tradition indeed.

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