Tuberculosis in Late Neolithic-Early Copper Age human skeletal remains from Hungary Annam  aria P  osa a, b, *, 1 , Frank Maixner c, 1 , Bal  azs Guszt  av Mende d , Kitti K € ohler d , Anett Oszt  as d , Christophe Sola e , Olivier Dutour f, g , Muriel Masson a , Erika Moln  ar a , Gy € orgy P  alfi a , Albert Zink c a Department of Biological Anthropology, University of Szeged, Szeged, Hungary b Department of Genetics, University of Szeged, Szeged, Hungary c Institute for Mummies and the Iceman, EURAC Research, Bolzano, Italy d Research Centre for the Humanities, Institute of Archaeology, Hungarian Academy of Sciences, Budapest, Hungary e Institut de Biologie Int egrative de la Cellule I2BC CEA-CNRS-Universit e Paris-Saclay, UMR9198, B^ at. 400 F-91405 ORSAY-Cedex, France f Laboratoire d’Anthropologie biologique Paul Broca, Ecole Pratique des Hautes Etudes, UMR 5199 PACEA, Universit e de Bordeaux, Pessac, France g Department of Anthropology, University of Western Ontario, Canada Keywords: Skeletal tuberculosis Late neolithic human samples aDNA Mycobacterium tuberculosis complex Carpathian basin summary Als ony ekeB atasz ek in Southern Hungary is one of the largest late Neolithic settlements and cemeteries excavated in Central Europe. In total, 2359 burials from the Late Neolithic e Early Copper Age Lengyel culture were found between 2006 and 2009 [1]. Anthropological investigations previously carried out on individuals from this site revealed an interesting paleopathological case of tuberculosis in the form of Pott's disease dated to the early 5 th millennium BC. In this study, selected specimens from this osteo- archeological series were subjected to paleomicrobiological analysis to establish the presence of MTBC bacteria. As all individuals showing clear osteological signs of TB infection belonged to a single grave group, 38 individuals from this grave group were analysed. The sample included the case of Pott's disease as well as individuals both with and without osseous TB manifestations. The detection of TB DNA in the individual with Pott's disease provided further evidence for the occurrence of TB in Neolithic populations of Europe. Moreover, our molecular analysis indicated that several other individuals of the same grave group were also infected with TB, opening the possibility for further analyses of this unique Neolithic skeletal series. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Tuberculosis (TB) is one of the oldest diseases and still has a high prevalence nowadays. The disease is pandemic, with 2.5 billion people on Earth infected by bacteria of the genus Mycobacterium [2]. The main human pathogens in this genus causing tuberculosis are Mycobacterium tuberculosis, Mycobacterium bovis and Myco- bacterium africanum, which belong together with Mycobacterium microti, Mycobacterium canetti, Mycobacterium caprae and Myco- bacterium pinnipedii to the so-called M. tuberculosis complex [3]. Members of M. tuberculosis complex (MTBC) derived from a com- mon ancestor, Mycobacterium protuberculosis, which evolved together with mankind [4e6]. Socio- and economic changes taking place during the Neolithic, including settlements, crop cultivation and animal domestication, led to a much closer contacts between humans and animals. These new living conditions for humans during Neolithic facilitated the transmission and spread of infec- tious diseases like TB between humans but also between humans and animals. The latter transmission pathway led to the long- lasting theory that M. tuberculosis evolved from M. bovis by trans- mission from cattle to humans during domestication [7]. Several studies, however, in particular genome sequencing, contradict this “bovis to human” scenario by confirming that MTB complex strains have undergone reductive evolution starting with an ancient form of M. tuberculosis which developed into modern M. tuberculosis * Corresponding author. Department of Biological Anthropology, University of Szeged, K€ oz ep fasor 52, H-6726 Szeged, Hungary. Tel./fax: þ36 (62)544 314. E-mail address: posa.annamaria@gmail.com (A. P osa). 1 These authors contributed equally to this work as first authors. Contents lists available at ScienceDirect Tuberculosis journal homepage: http://intl.elsevierhealth.com/journals/tube http://dx.doi.org/10.1016/j.tube.2015.02.011 1472-9792/© 2015 Elsevier Ltd. All rights reserved. Tuberculosis 95 (2015) S18eS22