Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA

Information

  • Research Project
  • 10276190
  • ApplicationId
    10276190
  • Core Project Number
    R35GM142939
  • Full Project Number
    1R35GM142939-01
  • Serial Number
    142939
  • FOA Number
    PAR-20-117
  • Sub Project Id
  • Project Start Date
    8/9/2021 - 3 years ago
  • Project End Date
    6/30/2026 - a year from now
  • Program Officer Name
    JANES, DANIEL E
  • Budget Start Date
    8/9/2021 - 3 years ago
  • Budget End Date
    6/30/2022 - 2 years ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
  • Award Notice Date
    8/9/2021 - 3 years ago

Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA

PROJECT SUMMARY The possibility of recovering ancient DNA (aDNA) molecules from archeological samples has yielded great opportunities for the study of human evolution and history. Compared to traditional datasets composed of a single time point collected in the present, aDNA allows for the detection of lost genetic lineages and enables the direct assessment of allele frequencies in different time transects. Technologies for obtaining genomic data from archeological material have catapulted the development of the field of paleogenomics, but statistical methods to leverage information from time-series genetic datasets lag behind these technological advances. Over the next five years, the Amorim Lab will develop and apply methods to study human host-pathogen coevolution and adaptation using aDNA. We seek to advance the field of paleogenomics by generating aDNA datasets that comprise large sample sizes per archeological site and developing new methods and approaches to leverage information from time-series genetic data. We will use these novel resources to study host-pathogen interactions during the outbreaks of the plague in Eurasia (e.g. the Black Death) and the period of contact between Indigenous peoples from South America and European colonizers. Contrasting models of population evolution, both analytical and computational, with observed allele frequencies and other summary statistics in different time transects, we will identify the genetic signatures of host-pathogen interactions, characterize the evolutionary processes involved in human response to pathogens, and infer the strength and timing of selective sweeps. In addition, we will characterize the Distribution of Fitness Effects (DFE) of new mutations in the human genome across different time transects and analyze its evolution in light of the environmental shifts caused by disease outbreaks and other events. This study represents an advance over the state-of-the-art knowledge in paleogenomics for its focus on evolutionary process not yet characterized with aDNA (in particular, host-pathogen coevolution), the characterization of the DFE using time-series data, and the development of new resources (datasets and methods). The Amorim Lab is uniquely positioned to accomplish these goals because of our experience in combining model-based approaches with genome data analysis from ancient and modern DNA, as well as our previous experience with the study of medieval Europeans and Native American populations.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    R35
  • Administering IC
    GM
  • Application Type
    1
  • Direct Cost Amount
    249175
  • Indirect Cost Amount
    103282
  • Total Cost
    352457
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    859
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIGMS:352457\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    CALIFORNIA STATE UNIVERSITY NORTHRIDGE
  • Organization Department
    BIOLOGY
  • Organization DUNS
    055752331
  • Organization City
    NORTHRIDGE
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    913308232
  • Organization District
    UNITED STATES