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{study} Our Ability To Digest Alcohol May Have Been Key To Our Survival

By Basoodler, Dec 3, 2014 | Updated: Dec 3, 2014 | | |
  1. Basoodler

    As we're sipping away on a glass of stout or Merlot, we probably take for granted our ability to digest the alcohol in the drink. Alcohol, or dietary ethanol (as scientists like to call it), is technically a toxin — imbibing too much can lead to a hangover and even poisoning, of course.

    But thanks to enzymes in our gut, and particularly one called ADH4, we can make use of the calories in alcohol. And, according to a new scientific paper, we gained that ability a very long time ago, at a critical moment in our evolution.

    Matthew Carrigan is an evolutionary biologist at Santa Fe College in Gainsville, Fla., and lead author on the paper. He discovered that the ADH4 enzyme started showing up in the ancestor we share with chimps and gorillas 10 million years ago, around the time when these ancestors started eating fallen, fermented fruit off the forest floor. The findings appear in the latest Proceedings of the National Academy of Sciences.

    That was a long time before we started making alcohol ourselves around 7,000 BC. And the timing was important, says Carrigan, because 10 million years ago, the climate was changing rapidly, and the East African forest ecosystem where our ancestors were roaming was replaced with more fragmented forests and grassland ecosystems. The change meant our tree-loving ancestors were probably spending more time on the ground.

    Down there on all fours, our ancestors had access to fruit that had fallen from the trees and was fermenting — so it had a buzzy kick. And that's when that ADH4 enzyme seemed to really come in handy.

    "The emergence of ADH4 in our ancestors wasn't slow and gradual; it was a rather abrupt shift of a large magnitude," Carrigan tells The Salt.

    To figure out when the enzyme might have become a regular in our gut, Carrigan used paleogenetics, an experimental approach in which gene sequences from contemporary species are used to estimate how proteins, and in this case enzymes, evolved over time.

    This ability to eat fermented fruit — not just ripe fruit — and use the alcohol for energy, as well as the sugars, vitamins and proteins in that fruit might have helped us survive the changing climate, Carrigan says. But, he says, it also elucidates another dimension of our relationship with alcohol.

    "There are hypotheses that the reason humans consume ethanol is because of our recent transition to farming, and how we learned how to ferment, grains or fruit, maybe because we wanted to escape consciousness," he says. "But my study shows that maybe it has its roots in our ancient history as fruitivores."

    The findings have intriguing implications for research into the evolutionary origins of alcoholism, Carrigan says. We humans have only been fermenting alcohol for 9,000 years, but his research shows we've actually been drinking it for millions of years. So when and why did our relationship to booze become problematic? That's a mystery that remains to be solved.

    December 03, 2014
    12:19 PM ET



  1. Basoodler
    Re: Our Ability To Digest Alcohol May Have Been Key To Our Survival


    Chemical analyses recently confirmed that the earliest alcoholic beverage in the world was a mixed fermented drink of rice, honey, and hawthorn fruit and/or grape.

    The residues of the beverage, dated ca. 7000–6600 BCE, were recovered from early pottery from Jiahu, a Neolithic village in the Yellow River Valley. This beverage currently predates the earliest evidence of grape wine from the Middle East by more than 500 years.

    Photo caption: Typical Neolithic burial at Jiahu, with pottery vessels containing a mixed fermented beverage (courtesy of Henan Institute of Cultural Relics and Archaeology).


    7000–6600 BCE

    Dr. Patrick McGovern
    Dr. Juzhong Zhang, University of Science and Technology of China
    Dr. Jigen Tang, Chinese Academy of Social Sciences
    Dr. Zhiqing Zhang, Henan Institute of Cultural Relics and Archaeology
    Dr. Gretchen R. Hall, Penn Museum
    Dr. Robert A. Moreau, U. S. Department of Agriculture
    Dr. Alberto Nuñez, U. S. Department of Agriculture
    Dr. Eric D. Butrym, Firmenich Corporation
    Dr. Michael P. Richards, University of Bradford
    Dr. Chen-shan Wang, Penn Museum
    Dr. Guangsheng Cheng, Chinese Academy of Sciences
    Dr. Zhijun Zhao, Chinese Academy of Social Sciences
    Dr. Changsui Wang, University of Science and Technology of China

    Chemical analyses of ancient organics absorbed, and preserved, in pottery jars from the Neolithic village of Jiahu, in Henan province, Northern China, have revealed that a mixed fermented beverage of rice, honey, and fruit was being produced as early as 9,000 years ago, approximately the same time that barley beer and grape wine were beginning to be made in the Middle East.

    In addition, liquids more than 3,000 years old, remarkably preserved inside tightly lidded bronze vessels, were chemically analyzed. These vessels from the capital city of Anyang and an elite burial in the Yellow River Basin, dating to the Shang and Western Zhou Dynasties (ca. 1250-1000 BCE), contained specialized rice and millet "wines." The beverages had been flavored with herbs, flowers, and/or tree resins, and are similar to herbal wines described in the Shang dynasty oracle inscriptions.

    The new discoveries, made by an international, multi-disciplinary team of researchers including the Penn Museum's archaeochemist Dr. Patrick McGovern, provide the first direct chemical evidence for early fermented beverages in ancient Chinese culture, thus broadening our understanding of the key technological and cultural roles that fermented beverages played in China.

    The discoveries and their implications for understanding ancient Chinese culture are published in the PNAS Early Edition (Proceedings of the National Academy of Sciences): "Fermented Beverages of Pre-and Proto-historic China," by Patrick E. McGovern, Juzhong Zhang, Jigen Tang, Zhiquing Zhang, Gretchen R. Hall, Robert A. Moreau, Alberto Nuñez, Eric D. Butrym, Michael P. Richards, Chen-shan Wang, Guangsheng Cheng, Zhijun Zhao, and Changsui Wang. Dr. McGovern worked with this team of researchers, associated with the University of Science and Technology of China in Hefei, the Institute of Archaeology in Beijing, the Institute of Cultural Relics and Archaeology of Henan Province, the U.S. Department of Agriculture, the Firmenich Corporation, Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany), and the Institute of Microbiology of the Chinese Academy of Sciences.

    Dr. McGovern first met with archaeologists and scientists, including his co-authors on the paper, in China in 2000, returning there in 2001 and 2002. Because of the great interest in using modern scientific techniques to investigate a crucial aspect of ancient Chinese culture, collaboration was initiated and samples carried back to the U.S. for analysis. Chemical tests of the pottery from the Neolithic village of Jiahu was of special interest, because it is some of the earliest known pottery from China. This site was already famous for yielding some of the earliest musical instruments and domesticated rice, as well as possibly the earliest Chinese pictographic writing. Through a variety of chemical methods including gas and liquid chromatography-mass spectrometry, infrared spectrometry, and stable isotope analysis, finger-print compounds were identified, including those for hawthorn fruit and/or wild grape, beeswax associated with honey, and rice.

    The prehistoric beverage at Jiahu, Dr. McGovern asserts, paved the way for unique cereal beverages of the proto-historic 2nd millennium BCE, remarkably preserved as liquids inside sealed bronze vessels of the Shang and Western Zhou Dynasties. The vessels had become hermetically sealed when their tightly fitting lids corroded, preventing evaporation. Numerous bronze vessels with these liquids have been excavated at major urban centers along the Yellow River, especially from elite burials of high-ranking individuals. Besides serving as burial goods to sustain the dead in the afterlife, the vessels and their contents can also be related to funerary ceremonies in which living intermediaries communicated with the deceased ancestor and gods in an altered state of consciousness after imbibing a fermented beverage.

    "The fragrant aroma of the liquids inside the tightly lidded jars and vats, when their lids were first removed after some three thousand years, suggested that they indeed represented Shang and Western Zhou fermented beverages, " Dr. McGovern noted. Samples of liquid inside vessels from the important capital of Anyang and the Changzikou Tomb in Luyi county were analyzed. The combined archaeochemical, archaeobotanical and archaeological evidence for the Changzikou Tomb and Anyang liquids point to their being fermented and filtered rice or millet "wines," either jiu or chang, its herbal equivalent, according to the Shang Dynasty oracle inscriptions. Specific aromatic herbs (e.g., wormword), flowers (e.g., chrysanthemum), and/or tree resins (e.g., China fir and elemi) had been added to the wines, according to detected compounds such as camphor and alpha-cedrene, beta-amyrin and oleanolic acid, as well as benzaldehyde, acetic acid, and short-chain alcohols characteristic of rice and millet wines.

    Both jiu and chang of proto-historic China were likely made by mold saccharification, a uniquely Chinese contribution to beverage-making in which an assemblage of mold species are used to break down the carbohydrates of rice and other grains into simple, fermentable sugars. Yeast for fermentation of the simple sugars enters the process adventitiously, either brought in by insects or settling on to large and small cakes of the mold conglomerate (qu) from the rafters of old buildings. As many as 100 special herbs, including wormwood, are used today to make qu, and some have been shown to increase the yeast activity by as much as seven-fold.

    For Dr. McGovern, who began his role in the Chinese wine studies in 2000, this discovery offers an exciting new chapter in our rapidly growing understanding of the importance of fermented beverages in human culture around the world. In 1990, he and colleagues Rudolph H. Michel and Virginia R. Badler first made headlines with the discovery of what was then the earliest known chemical evidence of wine, dating to ca. 3500-3100 BCE, from Godin Tepe in the Zagros Mountains of western Iran (see "Drink and Be Merry!: Infrared Spectroscopy and Ancient Near Eastern Wine" in Organic Contents of Ancient Vessels: Materials Analysis and Archaeological Investigation, eds. W. R. Biers and P.E. McGovern, MASCA Research Papers in Science and Archaeology, vol. 7, Philadelphia: MASCA, University of Pennsylvania Museum, University of Pennsylvania). That finding was followed up by the earliest chemically confirmed barley beer in 1992, inside another vessel from the same room at Godin Tepe that housed the wine jars. In 1994, chemical testing confirmed resinated wine inside two jars excavated by a Penn archaeological team at the Neolithic site of Hajji Firuz Tepe, Iran, dating to ca. 5400 BCE and some 2000 years earlier than the Godin Tepe jar. Dr. McGovern is author of Ancient Wine: The Search for the Origins of Viniculture (Princeton University Press, 2003).

    Dr. McGovern's research was made possible by support from the National Natural Science Foundation of China, the Henry Luce Foundation, and the National Science Foundation (2000-2001; award BCS-9911128). The GC-MS analyses were carried out in the Chemistry Department of Drexel University through the kind auspices of J. P. Honovich. Dr. McGovern also thanks the Institute of Archaeology in Beijing and Zhengzhou for logistical support and providing samples for analysis. Qin Ma Hui, Wuxiao Hong, Hsing-Tsung Huang, Shuicheng Li, Guoguang Luo, Victor Mair, Harold Olmo, Vernon Singleton, and Tiemei Chen variously advised on or facilitated the research. Changsui Wang, chairperson of the Archaeometry program at the University of Science and Technology of China in Hefei (Anhui Province) was untiring in his enthusiasm for the project, and personally accompanied Dr. McGovern on travels to excavations and institutes, where collaborations and meetings with key scientists and archaeologists were arranged

  2. Basoodler
    Re: Our Ability To Digest Alcohol May Have Been Key To Our Survival

    Hominids adapted to metabolize ethanol long before human-directed fermentation


    Matthew A. Carrigana,b,1,
    Oleg Uryasevb,
    Carole B. Fryeb,
    Blair L. Eckmanb,
    Candace R. Myersc,
    Thomas D. Hurleyc, and
    Steven A. Bennerb

    Department of Natural Sciences, Santa Fe College, Gainesville, FL 32606;

    Foundation for Applied Molecular Evolution, Gainesville, FL 32604; and
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202

    Edited by Robert Dudley, University of California, Berkeley, CA, and accepted by the Editorial Board October 28, 2014 (received for review March 4, 2014)


    Many modern human diseases are attributed to incompatibility between our current environment and the environment for which our genome is adapted. It is unclear whether this model applies to alcoholism. We investigated this possibility by studying alcohol dehydrogenase class IV (ADH4), the first enzyme exposed to ethanol in the digestive tract that is capable of metabolizing ethanol. We resurrected ancestral ADH4 enzymes from various points in the ∼70 million y of primate evolution and identified a single mutation occurring ∼10 million y ago that endowed our ancestors with a markedly enhanced ability to metabolize ethanol. This change occurred approximately when our ancestors adopted a terrestrial lifestyle and may have been advantageous to primates living where highly fermented fruit is more likely.


    Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate–ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.


    ↵1To whom correspondence should be addressed. Email: matthew.carrigan@sfcollege.edu.
    Author contributions: M.A.C. and S.A.B. designed research; M.A.C., O.U., C.B.F., and B.L.E. performed research; C.R.M. and T.D.H. contributed new reagents/analytic tools; M.A.C., O.U., and C.B.F. analyzed data; and M.A.C. and S.A.B. wrote the paper.
    The authors declare no conflict of interest.
    This article is a PNAS Direct Submission. R.D. is a guest editor invited by the Editorial Board.
    Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. KM972566–KM972576).

    This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1404167111/-/DCSupplemental.

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