RESUMO
As both a computational and an experimental endeavor, ancestral sequence reconstruction remains a timely and important technique. Modern approaches to conduct ancestral sequence reconstruction for proteins are built upon a conceptual framework from journal founder Emile Zuckerkandl. On top of this, work on maximum likelihood phylogenetics published in Journal of Molecular Evolution in 1996 was one of the first approaches for generating maximum likelihood ancestral sequences of proteins. From its computational history, future model development needs as well as potential applications in areas as diverse as computational systems biology, molecular community ecology, infectious disease therapeutics and other biomedical applications, and biotechnology are discussed. From its past in this journal, there is a bright future for ancestral sequence reconstruction in the field of evolutionary biology.