The term 'ancient DNA' (aDNA) is coming of age, with over 1,200 hits in the PubMed database, beginning in the early 1980s with the studies of 'molecular paleontology'. Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeogenetics, paleo-epidemiology, and many other areas. This change was brought by development of new strategies for coping with the challenges in studying aDNA due to damage and fragmentation, scarce samples, significant historical gaps, and limited applicability of population genetics methods. In this review, we describe the state-of-the-art achievements in aDNA studies, with particular focus on human evolution and demographic history. We present the current experimental and theoretical procedures for handling and analysing highly degraded aDNA. We also review the challenges in the rapidly growing field of ancient epigenomics. Advancement of aDNA tools and methods signifies a new era in population genetics and evolutionary medicine research.

Bioinformatics Center A A Kharkevich Institute for Information Transmission Problems Russian Academy of Sciences Moscow Russian Federation Center for Personalized Medicine Children's Hospital Los Angeles Los Angeles CA USA Spatial Sciences Institute University of Southern California Los Angeles CA USA

Center for Personalized Medicine Children's Hospital Los Angeles Los Angeles CA USA Spatial Sciences Institute University of Southern California Los Angeles CA USA

Department of Animal and Plant Sciences University of Sheffield Sheffield South Yorkshire UK

Department of Biology and Ecology Faculty of Science University of Ostrava Ostrava Czech Republic Bioinformatics Center A A Kharkevich Institute for Information Transmission Problems Russian Academy of Sciences Moscow Russian Federation

Department of Computational and Molecular Biology University of Southern California Los Angeles CA USA

Donskaya Archeologia Rostov Russia

Ecology and Evolution Unit Okinawa Institute of Science and Technology Graduate University Okinawa Japan

EPAM Systems Newtown PA USA

Institute of Evolutionary Medicine University of Zurich Zurich Switzerland

Research Center of Biotechnology RAS Moscow Russia Department of Biology Lomonosov Moscow State University Russia

School of Chemical and Biotechnology SASTRA University Tanjore India

School of Systems Biology George Mason University VA USA Research Centre for Medical Genetics Moscow Russia Atlas Biomed Group Moscow Russia

Vavilov Institute of General Genetics RAS Moscow Russia

Vavilov Institute of General Genetics RAS Moscow Russia F1 Genomics San Diego CA USA School of Systems Biology George Mason University VA USA

Vavilov Institute of General Genetics RAS Moscow Russia University of Massachusetts Medical School Worcester MA USA

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