I am investigating the evolution of Mycobacteria in two projects. In collaboration with Jane Buikstra, Alicia Wilbur, and Michael Rosenberg (SOLS), I am examining the evolutionary history of tuberculosis (TB) in the Americas and elsewhere by analyzing TB DNA extracted from lesions in prehistoric and protohistoric American remains (from both Native American and European individuals). The second project examines the exchange of pathogens, specifically M. tuberculosis and M. leprae, between humans and non-human primates and is in collaboration with Lisa Jones-Engel (University of Washington National Primate Research Center), Alicia Wilbur, and several other ASU faculty.
Evolutionary History of tuberculosis: An ancient DNA approach
AC Stone (PI)
Tuberculosis (TB), as a re-emerging infectious disease, is the culmination of a global history extending over three million years in the Old World and originating in Africa. Recent research in molecular genetics confirms what paleopathologists have long suspected – that Mycobacterium tuberculosis was pathogenic for ancient Americans long before late 15th century European contact. The goal of this project is to analyze DNA from ancient strains of M. tuberculosis in order to integrate New World and Old World samples with modern strains in a phylogenetic framework, thus addressing questions about the evolutionary history of TB. Specifically, we propose to characterize strains from the earliest Old World skeletal cases of disseminated TB, explore the relationship of these early strains to those found in Britain by Iron Age/Roman times, consider the relationship between Old and New World TB prior to and following the 16th century era of European Exploration, and assess whether the increase in prevalence of tuberculosis during the 17th and 18th centuries in Europe was due to the spread of new strains. This work is in collaboration with Dr. Jane Buikstra (Center for Bioarchaeological Research, SHESC, ASU).
This research is being supported by the National Science Foundation (BCS-0612222).
AC Stone (Co-PI)
Disease exchange between humans and other animals has been an important adaptive pressure during our evolutionary history. However, the processes by which this occurs are poorly understood. Thus far, research has focused on infectious organisms that likely became human-specific during the transition to agriculture. More recently, the importance of monkeys and apes (non-human primates) as sources of infectious agents that are now adapted to humans has been highlighted because of the HIV epidemic. It is likely that non-human primates have long been important sources of new pathogens because of their close evolutionary relationship to us. The biological similarities mean that pathogens require few changes to make the “jump” to humans. Nonhuman primates may also serve as reservoirs for diseases that affect both them and us (and vice versa), thwarting both primate conservation and human public health efforts at containment and eradication. We are investigating the infectious disease exchange between human and nonhuman primates using two mycobacterial species —Mycobacterium tuberculosis and M. leprae—as case studies. Our project has two major components. First, we are collecting samples from humans and nonhuman primates in areas of the world where they live sympatrically, and where different lineages of the Order Primates can be examined. Samples are tested for the presence of DNA from M. tuberculosis and M. leprae, and strain-typing of positive samples will be performed to determine routes of transmission and epidemiological information such as disease prevalence in various nonhuman primate species, countries, and contexts of contact with humans. The second component involves using the data generated to model parameters that would have been required to maintain these diseases in antiquity in ancestral primate species and to model how the diseases may have spread in various primate taxa (and during the origin and dispersal of Homo sapiens throughout the globe). To date, we have obtained over 600 samples, and we have detected both M. tuberculosis and M. leprae in our samples. Interestingly, preliminary analyses indicates that areas where TB prevalence is high in humans also show high rates of positive M. tuberculosis DNA in nonhuman primates. We hypothesize that our primate ancestors also shared mycobacteria within and between species, and that an understanding of the past and present interactions between primates and mycobacteria will provide baseline data to inform current and future public health, conservation, and diagnostic/treatment efforts. We have received initial funding from the Late Lessons initiative (ASU) and plan to apply for additional funds from other sources.
For more information see: http://shesc.asu.edu/node/539
Genetic and Environmental Susceptibility to Tuberculosis
I am also beginning a new project in collaboration with Dr. Magdalena Hurtado (SHESC, Arizona State University) to examine genetic and environmental susceptibility to tuberculosis among the Ache and Ava of Paraguay. Tuberculosis is a significant health problem for the majority of the world’s populations and a growing body of evidence indicates that host genetics play an important role in determining susceptibility and resistance to the disease. Incidence of tuberculosis in Native American populations since European contact has been high; however, relatively little research into the genetics of susceptibility has been undertaken in these groups. The proposed project will examine loci that have been associated with tuberculosis in different populations worldwide including the human leukocyte antigen (HLA), vitamin D receptor (VDR), natural resistance-associated macrophage protein 1 (NRAMP1), mannose binding lectin (MBL) and tumor necrosis factor a loci. We have preliminary data from VDR, NRAMP1 and MBL (Wilbur et al. 2007, Tuberculosis 87:329-37). In addition, microsatellite loci from throughout the genome will be used to scan for other genes associated with tuberculosis susceptibility. The ability to detect tuberculosis DNA in cheek swabs from exposed individuals is also being tested as a potential method of diagnosis. This could ease the difficulty of obtaining sputum samples and speed the time it takes to diagnose the disease.