Although brewer’s yeast (Saccharomyces cerevisiae) is one of the best studied model organisms, whose genome was sequenced before that of humans, to this day we know shockingly little about its natural ecology, where it originated, and how it made its way into human hands to become one of the earliest organisms to be domesticated. Currently thought of as an ecological generalist, I instead propose that S. cerevisiae originated in Africa in association with the marula fruit (Sclerocarya birrea), and was spread around the world by migrating humans along with fruit flies (Drosophila melanogaster). I propose to isolate and sequence microbes naturally growing within fruits across a north-south gradient in Africa following routes of early human migration, and to show that brewer’s yeast and its high ethanol tolerance first evolved in South Africa. I am explicitly interested in evaluating a genomic signature of domestication, e.g., by estimating the age of domestication-associated alleles, and building a global population demographic model of this charismatic microbe. An African signature of yeast domestication could have major implications for the origins of civilization, since this would imply that intentional alcohol production was commonplace before the widespread use of agriculture. It may also result in discovery of pre-domestication varieties of brewer’s yeast that express novel functions with potential industrial and commercial applications.