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Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA

Award Number: R35GM142939
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/09/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $350,437 )
2024	2024	THE UNIVERSITY CORPORATION	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	6/10/2024	NON-COMPETING CONTINUATION	$350,437
														Subtotal = $350,437

Issue Date FY: 2023 ( Subtotal = $342,644 )
2023	2023	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	6/12/2023	NON-COMPETING CONTINUATION	$342,644
														Subtotal = $342,644

Issue Date FY: 2022 ( Subtotal = $358,782 )
2022	2022	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	6/8/2022	NON-COMPETING CONTINUATION	$358,782
														Subtotal = $358,782

Issue Date FY: 2021 ( Subtotal = $352,457 )
2021	2021	UNIVERSITY CORPORATION, THE	18111 NORDHOFF ST	NORTHRIDGE	CA	91330	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	8/9/2021	NEW	$352,457
														Subtotal = $352,457

Grand Total All Awards = $1,404,320

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Characterizing Human-Pathogen Interactions and Natural Selection with Ancient DNA

Award Number: R35GM142939

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/09/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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