![]() ![]() In 1984, DNA from a museum specimen of quagga, an equid species that went extinct in the nineteenth century, was successfully sequenced ( 1), thus marking the birth of the field of ancient DNA (aDNA) research. We then go on to highlight their most important applications to evolutionary inference and outline where research is heading in the upcoming years. In this review, we introduce these three major categories of ancient biomolecules, summarize the history of their study, and discuss the foundations and frontiers of the field. While deoxyribonucleic acids (DNA) can dissect evolutionary processes with the highest resolution, proteins and lipids are important on longer temporal scales and in geographic areas that are less favorable to DNA preservation. The categories of ancient molecules that have arguably made the biggest contribution to elucidating evolutionary history to date are nucleic acids, proteins, and lipids. Ancient molecules, conversely, offer a direct window into the biological past and allow us to track evolutionary processes in real time. However, such analyses provide only indirect evidence of the drivers and mechanisms that created present-day biodiversity. Prior to this, evolutionary inferences had been drawn almost exclusively from molecular analyses of living organisms and the observation of phenotypic traits in fossils. Over the last few decades, studies of ancient biomolecules have transformed our understanding of the evolutionary history of life on Earth. Here, we discuss the history and current state of ancient biomolecule research, its applications to evolutionary inference, and future directions for this young and exciting field. This progress has been made possible by continuous technical innovations in analytical methods, enhanced criteria for the selection of ancient samples, integrated experimental methods, and advanced computational approaches. Sampling frequencies and the spatial and temporal scope of studies have also increased markedly, and with them the size and quality of the data sets generated. Researchers now successfully retrieve nucleotide and amino acid sequences, as well as lipid signatures, from progressively older samples, originating from geographic areas and depositional environments that, until recently, were regarded as hostile to long-term preservation of biomolecules. Though initially fraught with many challenges, today the field stands on firm foundations. ![]() Over the past three decades, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Evershed, 6 and Eske Willerslev 1,2,8ġCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark email:, ĢDepartment of Zoology, University of Cambridge, Cambridge CB2 3EJ, United KingdomģNatural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, DenmarkĤDepartment of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, GermanyĥComputational Systems Biochemistry, Max Planck Institute of Biochemistry, 82152 Martinsried, GermanyĦOrganic Geochemistry Unit, School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom email: ħDepartment of Anthropology and Archaeology, University of Bristol, Bristol BS8 1UU, United KingdomĨWellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, United Kingdom ![]() Víctor Moreno-Mayar, 1 Yucheng Wang, 1 Martin Sikora, 1 Lasse Vinner, 1 Jürgen Cox, 5 Richard P. Allentoft, 1 Peter de Barros Damgaard, 1 Petra Gutenbrunner, 5 Julie Dunne, 6 Simon Hammann, 6,7 Mélanie Roffet-Salque, 6 Melissa Ilardo, 1 J. Enrico Cappellini, 1,* Ana Prohaska, 2,* Fernando Racimo, 1 Frido Welker, 3,4 Mikkel Winther Pedersen, 2 Morten E.
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