One trend in modern medicine attributes human disease to an incomplete adaptation of our genome to challenges newly presented by civilization. For example, modern humans interact with ethanol ("alcohol" in the vernacular) in ways important for survival, for its calories and its ability to preserve food. However, human interaction with ethanol also leads to disease, especially in certain genotypes.
Bulk fermentation requires technology: pottery, glass, and the like. Thus, most observers infer that ethanol was not part of our Paleolithic diet, when these technologies were not available. In this talk, we will present experiments that support a very different view.
To gain a molecular perspective on the interaction between our ancestors and alcohol, we collected sequences for genes encoding "class 4" alcohol dehydrogenases (ADH4) from two dozen primates, including apes, Old World and New World monkeys, and lemurs. ADH4 is abundant in the esophagus, stomach, and intestine, making it the first alcohol-metabolizing enzyme to encounter imbibed ethanol.
From these data and a tree representing the evolution of primates, we inferred the sequences of a dozen ancestral primate ADH4 proteins dating back 60 million years, nearly to the age of the dinosaurs. These ancient ADH4's were then resurrected for study in the laboratory.
The evolution of the behaviors of these ancestral enzymes were striking. While the enzymes from our most ancient primate ancestors were largely inactive against ethanol, they could metabolize other alcohols, including "terpene" alcohols abundant in the leaves of plants. Indeed, the last common ancestor of {gorilla, chimpanzee, human} and orangutan, living 16-21 million years ago, could not effectively metabolize imbibed ethanol.
However, by 6-12 million years before pesent (and well before the Paleolithic), this situation had dramatically changed. Our last common ancestor with gorillas and chimpanzees had evolved a digestion fully able to metabolize imbibed ethanol, at levels found in fermenting fruits.
This talk will discuss these results, and correlate with them with fossils of our ancestors, including Ardipithecus, Sahelanthropus, Orrorin, and Sivapithecus. These were the first hominids adapted for forest walking and carrying food, as wells as tree climbing. Thus, they were also our first ancestors able to gather fermenting fruit picked from the ground. This has implications, not only for the origin of our "human-ness" in one of its more widely appreciated aspects, but also for the health issues related to ethanol today.