Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Edited by Robert Dudley, University of California, Berkeley, CA, and accepted by the Editorial Board October 28, 2014 (received for review March 4, 2014)
Significance
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.
Abstract
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.
Footnotes
- ↵1To whom correspondence should be addressed. Email: matthew.carrigan{at}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).
See Commentary on page 308.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1404167111/-/DCSupplemental.
Evolution of hominid ethanol metabolism
Article Classifications
- Biological Sciences
- Evolution
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.
See related content: